Step 12.5: Fernando Object-Based Astrocyte lncRNA Analysis

Cluster-based differential expression and lncRNA candidate discovery from Fernando-defined astrocyte states

1 Setup: Environment and Data

This file starts from the astrocyte object generated in Step 11.5.

The input object should already contain:

Fernando-defined astrocyte cells
astrocyte subclusters
reactive / inflammatory / stress / ECM module scores
condition information

The main biological goal is to identify lncRNAs associated with a cluster-defined astrocyte state transition:

Homeostatic-like astrocytes
→ reactive / stress-like PD-enriched astrocytes

This is an astrocyte state analysis, not a broad cell-type discovery analysis.

library(Seurat)
library(tidyverse)
library(patchwork)
library(AnnotationDbi)
library(org.Hs.eg.db)

set.seed(1234)

project_dir <- "/Users/yoshimurasouhei/Downloads/010_school/4年生/bioinfomaticsリサーチクラークシップ/PD_2026"

input_path <- file.path(
  project_dir,
  "results",
  "Step11_5_fernando_astrocyte_reclustering",
  "SO_astro_step11_5_fernando_reclustered_scored.rds"
)

results_dir <- file.path(
  project_dir,
  "results",
  "Step12_5_fernando_astrocyte_lncRNA_analysis"
)

dir.create(results_dir, recursive = TRUE, showWarnings = FALSE)

SO_astro <- readRDS(input_path)

DefaultAssay(SO_astro) <- "RNA"

if ("Assay5" %in% class(SO_astro[["RNA"]])) {
  SO_astro <- JoinLayers(SO_astro, assay = "RNA")
}

SO_astro
An object of class Seurat 
87674 features across 5259 samples within 2 assays 
Active assay: RNA (47773 features, 2000 variable features)
 3 layers present: counts, data, scale.data
 1 other assay present: SCT
 4 dimensional reductions calculated: pca, umap, harmony, umap_astro
colnames(SO_astro@meta.data)
 [1] "orig.ident"                   "nCount_RNA"                  
 [3] "nFeature_RNA"                 "percent_mt"                  
 [5] "percent_rib"                  "Damage_score"                
 [7] "scDblFinder.score"            "scDblFinder.class"           
 [9] "sparsity"                     "Subject"                     
[11] "Sample"                       "condition"                   
[13] "APOE_e4"                      "age"                         
[15] "Sex"                          "PMI"                         
[17] "Braak"                        "MMSE"                        
[19] "DRS"                          "snRNA.seq"                   
[21] "snRNA.seq_Batch_visto"        "cond_sex"                    
[23] "nCount_SCT"                   "nFeature_SCT"                
[25] "SCT_snn_res.1"                "seurat_clusters"             
[27] "S.Score"                      "G2M.Score"                   
[29] "Phase"                        "preint_clusters1"            
[31] "unintegrated_clusters"        "SCT_snn_res.0.5"             
[33] "Cell_types"                   "fernando_celltype_annotation"
[35] "condition_use"                "astro_original_identity"     
[37] "RNA_snn_res.0.3"              "Astro_identity_score1"       
[39] "Reactive_astro_score1"        "Inflammatory_score1"         
[41] "Stress_score1"                "ECM_score1"                  
table(SO_astro$seurat_clusters)

  0   1   2   3   4   5   6   7   8   9  10  11 
921 806 706 516 443 432 431 423 249 210  62  60 
table(SO_astro$condition)

   C   PD 
2336 2923 
score_cols <- c(
  "Astro_identity_score1",
  "Reactive_astro_score1",
  "Inflammatory_score1",
  "Stress_score1",
  "ECM_score1"
)

missing_score_cols <- setdiff(score_cols, colnames(SO_astro@meta.data))

if (length(missing_score_cols) > 0) {
  stop(
    paste(
      "Missing score columns from Step 11.5:",
      paste(missing_score_cols, collapse = ", ")
    )
  )
}

2 Step 12.1: Refine Astrocyte State Annotation

Here, the main state definition is cluster-based, not quartile-based.

Based on Step 11.5 cluster summaries, the main groups are:

Reactive_stress_like_PD:
  clusters 0, 6, 8

Homeostatic_like_C:
  clusters 2, 4, 5

Excluded from main binary DE:
  clusters 1, 3, 7, 9, 10, 11

Cluster 10 is kept out of the main homeostatic group because it is small, mixed by condition, and has weaker astrocyte identity compared with cluster 2.

The combined reactivity score is calculated only for visualization and summary. It is not used to define the main DE groups.

SO_astro$astro_cluster <- as.character(SO_astro$seurat_clusters)

reactive_stress_clusters <- c("0", "6", "8")
homeostatic_clusters <- c("2", "4", "5")
minor_or_intermediate_clusters <- c("9", "10", "11")

SO_astro$astro_state_refined <- case_when(
  SO_astro$astro_cluster %in% reactive_stress_clusters ~ "Reactive_stress_like_PD",
  SO_astro$astro_cluster %in% homeostatic_clusters ~ "Homeostatic_like_C",
  SO_astro$astro_cluster == "3" ~ "PD_enriched_low_reactivity",
  SO_astro$astro_cluster == "1" ~ "Mixed_PD_biased",
  SO_astro$astro_cluster == "7" ~ "Mixed_balanced",
  SO_astro$astro_cluster %in% minor_or_intermediate_clusters ~ "Minor_or_intermediate",
  TRUE ~ "Unassigned"
)

SO_astro$astro_state_refined <- factor(
  SO_astro$astro_state_refined,
  levels = c(
    "Homeostatic_like_C",
    "Reactive_stress_like_PD",
    "PD_enriched_low_reactivity",
    "Mixed_PD_biased",
    "Mixed_balanced",
    "Minor_or_intermediate",
    "Unassigned"
  )
)

table(SO_astro$astro_cluster, SO_astro$astro_state_refined)
    
     Homeostatic_like_C Reactive_stress_like_PD PD_enriched_low_reactivity
  0                   0                     921                          0
  1                   0                       0                          0
  10                  0                       0                          0
  11                  0                       0                          0
  2                 706                       0                          0
  3                   0                       0                        516
  4                 443                       0                          0
  5                 432                       0                          0
  6                   0                     431                          0
  7                   0                       0                          0
  8                   0                     249                          0
  9                   0                       0                          0
    
     Mixed_PD_biased Mixed_balanced Minor_or_intermediate Unassigned
  0                0              0                     0          0
  1              806              0                     0          0
  10               0              0                    62          0
  11               0              0                    60          0
  2                0              0                     0          0
  3                0              0                     0          0
  4                0              0                     0          0
  5                0              0                     0          0
  6                0              0                     0          0
  7                0            423                     0          0
  8                0              0                     0          0
  9                0              0                   210          0
table(SO_astro$astro_state_refined, SO_astro$condition)
                            
                                C   PD
  Homeostatic_like_C         1578    3
  Reactive_stress_like_PD       8 1593
  PD_enriched_low_reactivity   12  504
  Mixed_PD_biased             303  503
  Mixed_balanced              211  212
  Minor_or_intermediate       224  108
  Unassigned                    0    0
reactivity_score_matrix <- SO_astro@meta.data[, c(
  "Reactive_astro_score1",
  "Inflammatory_score1",
  "Stress_score1",
  "ECM_score1"
)]

SO_astro$combined_reactivity_score_z <- rowMeans(
  scale(reactivity_score_matrix),
  na.rm = TRUE
)

summary(SO_astro$combined_reactivity_score_z)
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
-1.2683 -0.5273 -0.1045  0.0000  0.4100  3.7505 
astro_state_cluster_summary <- SO_astro@meta.data %>%
  mutate(
    astro_cluster = as.character(seurat_clusters),
    astro_state_refined = as.character(astro_state_refined)
  ) %>%
  group_by(astro_cluster, astro_state_refined) %>%
  summarise(
    n_cells = n(),
    mean_astro_identity = mean(Astro_identity_score1, na.rm = TRUE),
    mean_combined_reactivity_z = mean(combined_reactivity_score_z, na.rm = TRUE),
    mean_reactive = mean(Reactive_astro_score1, na.rm = TRUE),
    mean_inflammatory = mean(Inflammatory_score1, na.rm = TRUE),
    mean_stress = mean(Stress_score1, na.rm = TRUE),
    mean_ecm = mean(ECM_score1, na.rm = TRUE),
    percent_PD = mean(condition == "PD", na.rm = TRUE),
    percent_C = mean(condition == "C", na.rm = TRUE),
    .groups = "drop"
  ) %>%
  arrange(desc(mean_combined_reactivity_z))

astro_state_cluster_summary
# A tibble: 12 × 11
   astro_cluster astro_state_refined        n_cells mean_astro_identity
   <chr>         <chr>                        <int>               <dbl>
 1 0             Reactive_stress_like_PD        921               1.05 
 2 8             Reactive_stress_like_PD        249               0.510
 3 6             Reactive_stress_like_PD        431               0.463
 4 4             Homeostatic_like_C             443               1.08 
 5 5             Homeostatic_like_C             432               1.21 
 6 1             Mixed_PD_biased                806               0.636
 7 11            Minor_or_intermediate           60               0.775
 8 9             Minor_or_intermediate          210               0.581
 9 3             PD_enriched_low_reactivity     516               0.706
10 2             Homeostatic_like_C             706               0.903
11 7             Mixed_balanced                 423               0.472
12 10            Minor_or_intermediate           62               0.691
# ℹ 7 more variables: mean_combined_reactivity_z <dbl>, mean_reactive <dbl>,
#   mean_inflammatory <dbl>, mean_stress <dbl>, mean_ecm <dbl>,
#   percent_PD <dbl>, percent_C <dbl>
astro_state_group_summary <- SO_astro@meta.data %>%
  mutate(
    astro_cluster = as.character(seurat_clusters),
    astro_state_refined = as.character(astro_state_refined)
  ) %>%
  group_by(astro_state_refined) %>%
  summarise(
    n_cells = n(),
    mean_astro_identity = mean(Astro_identity_score1, na.rm = TRUE),
    mean_combined_reactivity_z = mean(combined_reactivity_score_z, na.rm = TRUE),
    mean_reactive = mean(Reactive_astro_score1, na.rm = TRUE),
    mean_inflammatory = mean(Inflammatory_score1, na.rm = TRUE),
    mean_stress = mean(Stress_score1, na.rm = TRUE),
    mean_ecm = mean(ECM_score1, na.rm = TRUE),
    percent_PD = mean(condition == "PD", na.rm = TRUE),
    percent_C = mean(condition == "C", na.rm = TRUE),
    clusters_included = paste(sort(unique(astro_cluster)), collapse = ", "),
    .groups = "drop"
  ) %>%
  arrange(desc(mean_combined_reactivity_z))

astro_state_group_summary
# A tibble: 6 × 11
  astro_state_refined        n_cells mean_astro_identity mean_combined_reactiv…¹
  <chr>                        <int>               <dbl>                   <dbl>
1 Reactive_stress_like_PD       1601               0.807                  0.513 
2 Mixed_PD_biased                806               0.636                 -0.0523
3 Homeostatic_like_C            1581               1.04                  -0.167 
4 PD_enriched_low_reactivity     516               0.706                 -0.348 
5 Minor_or_intermediate          332               0.637                 -0.363 
6 Mixed_balanced                 423               0.472                 -0.508 
# ℹ abbreviated name: ¹​mean_combined_reactivity_z
# ℹ 7 more variables: mean_reactive <dbl>, mean_inflammatory <dbl>,
#   mean_stress <dbl>, mean_ecm <dbl>, percent_PD <dbl>, percent_C <dbl>,
#   clusters_included <chr>
p_state <- DimPlot(
  SO_astro,
  reduction = "umap_astro",
  group.by = "astro_state_refined",
  label = TRUE,
  repel = TRUE,
  pt.size = 0.5
) +
  labs(title = "Cluster-Based Refined Astrocyte State Annotation")

p_score <- FeaturePlot(
  SO_astro,
  features = "combined_reactivity_score_z",
  reduction = "umap_astro",
  pt.size = 0.5
) +
  labs(title = "Z-scored Combined Astrocyte Reactivity Score")

p_state | p_score

SO_astro$astro_DE_group <- case_when(
  SO_astro$astro_state_refined == "Reactive_stress_like_PD" ~ "Reactive_stress_like_PD",
  SO_astro$astro_state_refined == "Homeostatic_like_C" ~ "Homeostatic_like_C",
  TRUE ~ NA_character_
)

SO_astro$astro_DE_group <- factor(
  SO_astro$astro_DE_group,
  levels = c("Homeostatic_like_C", "Reactive_stress_like_PD")
)

table(SO_astro$astro_DE_group, useNA = "ifany")

     Homeostatic_like_C Reactive_stress_like_PD                    <NA> 
                   1581                    1601                    2077 
table(SO_astro$astro_DE_group, SO_astro$condition, useNA = "ifany")
                         
                             C   PD
  Homeostatic_like_C      1578    3
  Reactive_stress_like_PD    8 1593
  <NA>                     750 1327
write.csv(
  astro_state_cluster_summary,
  file.path(results_dir, "Step12_1_refined_astrocyte_state_cluster_summary.csv"),
  row.names = FALSE
)

write.csv(
  astro_state_group_summary,
  file.path(results_dir, "Step12_1_refined_astrocyte_state_group_summary.csv"),
  row.names = FALSE
)

write.csv(
  as.data.frame.matrix(table(SO_astro$astro_state_refined, SO_astro$condition)),
  file.path(results_dir, "Step12_1_refined_astrocyte_state_condition_table.csv")
)

write.csv(
  as.data.frame.matrix(table(SO_astro$astro_cluster, SO_astro$astro_state_refined)),
  file.path(results_dir, "Step12_1_cluster_to_refined_state_table.csv")
)

3 Step 12.2: Define Comparison Groups for Differential Expression

We define two main comparisons:

1. Reactive_stress_like_PD vs Homeostatic_like_C
2. PD vs C within Fernando-defined astrocytes

The first comparison prioritizes cluster-defined astrocyte state-associated genes.
The second comparison prioritizes disease-associated genes across all Fernando-defined astrocytes.

SO_astro_main_DE <- subset(
  SO_astro,
  subset = !is.na(astro_DE_group)
)

SO_astro_main_DE$astro_DE_group <- droplevels(SO_astro_main_DE$astro_DE_group)

table(SO_astro_main_DE$astro_DE_group)

     Homeostatic_like_C Reactive_stress_like_PD 
                   1581                    1601 
table(SO_astro_main_DE$astro_DE_group, SO_astro_main_DE$condition)
                         
                             C   PD
  Homeostatic_like_C      1578    3
  Reactive_stress_like_PD    8 1593
min_pct_use <- 0.05
logfc_threshold_use <- 0.10
p_adj_cutoff <- 0.05
lncRNA_logfc_cutoff <- 0.25

min_pct_use
[1] 0.05
logfc_threshold_use
[1] 0.1
p_adj_cutoff
[1] 0.05
lncRNA_logfc_cutoff
[1] 0.25

4 Step 12.3: Differential Expression Analysis

We run DE for:

Reactive_stress_like_PD vs Homeostatic_like_C
PD vs C
Idents(SO_astro_main_DE) <- SO_astro_main_DE$astro_DE_group

astro_reactive_vs_homeostatic_DE <- FindMarkers(
  SO_astro_main_DE,
  ident.1 = "Reactive_stress_like_PD",
  ident.2 = "Homeostatic_like_C",
  min.pct = min_pct_use,
  logfc.threshold = logfc_threshold_use,
  test.use = "wilcox"
) %>%
  rownames_to_column("gene") %>%
  arrange(p_val_adj, desc(avg_log2FC))

astro_reactive_vs_homeostatic_DE %>% head(20)
              gene         p_val avg_log2FC pct.1 pct.2     p_val_adj
1            MACF1 4.911134e-218  1.3377014 0.978 0.944 2.346196e-213
2           CTNNA3 6.268922e-193 -2.9109371 0.179 0.664 2.994852e-188
3           SAMD4A 1.188064e-190  1.8055224 0.893 0.698 5.675737e-186
4           CHI3L1 4.366689e-185  3.9070337 0.590 0.132 2.086099e-180
5          SHROOM3 3.717934e-172 -2.2315482 0.247 0.716 1.776169e-167
6            LAMA2 1.114688e-169 -3.3695726 0.083 0.533 5.325197e-165
7            MDGA2 3.974630e-158 -3.7057221 0.064 0.479 1.898800e-153
8           MALAT1 1.576425e-154 -1.0845420 0.999 0.999 7.531054e-150
9           SORBS1 1.026837e-147  0.9546918 0.964 0.932 4.905508e-143
10           NEAT1 6.735259e-147  1.3745627 0.982 0.973 3.217635e-142
11         SLC14A1 1.246036e-144 -2.1177526 0.463 0.815 5.952688e-140
12     MIR3171HG.1 1.104515e-140 -5.9661639 0.011 0.357 5.276599e-136
13         SPARCL1 7.560531e-140 -1.2279617 0.775 0.950 3.611892e-135
14           MEIS2 6.270658e-139 -1.8654372 0.251 0.685 2.995682e-134
15 ENSG00000299261 1.274055e-136 -3.9455646 0.035 0.397 6.086541e-132
16           TMTC2 8.230734e-136  2.8653109 0.618 0.249 3.932068e-131
17           PRKCA 2.090744e-127  1.1960313 0.908 0.835 9.988109e-123
18           NTRK2 4.556233e-125 -1.1765710 0.681 0.911 2.176649e-120
19          SLC4A4 3.863073e-124 -1.2609661 0.600 0.884 1.845506e-119
20           HSPH1 9.417259e-122  4.1160810 0.443 0.096 4.498907e-117
Idents(SO_astro) <- SO_astro$condition

astro_PD_vs_C_DE <- FindMarkers(
  SO_astro,
  ident.1 = "PD",
  ident.2 = "C",
  min.pct = min_pct_use,
  logfc.threshold = logfc_threshold_use,
  test.use = "wilcox"
) %>%
  rownames_to_column("gene") %>%
  arrange(p_val_adj, desc(avg_log2FC))

astro_PD_vs_C_DE %>% head(20)
          gene         p_val avg_log2FC pct.1 pct.2     p_val_adj
1       MALAT1 3.904114e-208 -1.0785343 0.999 0.999 1.865112e-203
2       CTNNA3 8.235943e-169 -2.2641051 0.266 0.575 3.934557e-164
3      SHROOM3 5.544921e-167 -1.6831448 0.313 0.653 2.648975e-162
4  MIR3171HG.1 1.078193e-163 -5.3019563 0.013 0.261 5.150851e-159
5        MDGA2 1.934560e-160 -2.7634112 0.109 0.416 9.241972e-156
6        MACF1 5.147090e-160  0.9162958 0.953 0.929 2.458920e-155
7       SORBS1 3.055967e-153  0.7907757 0.949 0.905 1.459927e-148
8        LAMA2 1.413994e-120 -2.0908767 0.171 0.449 6.755073e-116
9       CHI3L1 2.793107e-118  2.9560471 0.409 0.143 1.334351e-113
10       NEAT1 6.966431e-117  0.8786913 0.978 0.969 3.328073e-112
11      MT-ND3 4.478098e-113  0.9905999 0.900 0.743 2.139322e-108
12        DGKB 2.051512e-112 -1.5855716 0.249 0.522 9.800688e-108
13      SLC4A4 5.277187e-111 -0.9956392 0.620 0.821 2.521071e-106
14      SAMD4A 3.252936e-110  1.2140910 0.811 0.673 1.554025e-105
15       TMTC2 2.705426e-104  1.6778367 0.571 0.301  1.292463e-99
16    HSP90AA1 9.360653e-103  1.3043607 0.741 0.561  4.471865e-98
17       HSPH1 7.423274e-102  3.2857209 0.342 0.103  3.546321e-97
18       PAMR1 2.030730e-101 -1.0918818 0.431 0.686  9.701405e-97
19         DST 5.265388e-101  0.8461550 0.934 0.923  2.515434e-96
20     SPARCL1  1.010250e-99 -0.9123379 0.796 0.905  4.826269e-95

5 Step 12.4: Cluster-Specific DE Analysis

Here we extract markers for each astrocyte subcluster.

These are subcluster/state markers, not broad astrocyte identity markers.

Idents(SO_astro) <- SO_astro$seurat_clusters

astro_cluster_markers <- FindAllMarkers(
  SO_astro,
  only.pos = TRUE,
  min.pct = min_pct_use,
  logfc.threshold = logfc_threshold_use,
  test.use = "wilcox"
) %>%
  arrange(cluster, p_val_adj, desc(avg_log2FC))

astro_cluster_markers %>% head(30)
                        p_val avg_log2FC pct.1 pct.2     p_val_adj cluster
MACF1           8.379025e-304   1.449995 0.991 0.932 4.002912e-299       0
TPST1           2.641441e-292   2.635258 0.822 0.318 1.261896e-287       0
ARHGEF3         3.696520e-271   2.862048 0.724 0.223 1.765939e-266       0
CD44            1.474182e-265   1.972104 0.924 0.519 7.042612e-261       0
CHI3L1          1.562677e-233   2.730023 0.680 0.209 7.465376e-229       0
COLEC12         2.766009e-230   2.613918 0.775 0.342 1.321405e-225       0
SULF1           9.542085e-214   3.711245 0.434 0.066 4.558540e-209       0
ENSG00000297939 7.032475e-212   3.087899 0.488 0.090 3.359624e-207       0
SLC44A3-AS1     8.742003e-209   2.631803 0.685 0.251 4.176317e-204       0
ENSG00000228408 1.257367e-207   3.066317 0.579 0.156 6.006821e-203       0
DST             4.170632e-201   1.484174 0.965 0.921 1.992436e-196       0
ACTN1           1.419066e-193   3.143134 0.507 0.119 6.779304e-189       0
SAMD4A          3.786126e-183   1.600419 0.912 0.715 1.808746e-178       0
CRISPLD1        6.660049e-183   3.007689 0.507 0.129 3.181705e-178       0
MAP3K14         7.300518e-181   2.831615 0.549 0.157 3.487676e-176       0
SLC39A14        7.773643e-176   2.528831 0.570 0.174 3.713702e-171       0
ZFYVE28         2.131224e-175   2.314126 0.609 0.210 1.018149e-170       0
ANO6            5.297830e-167   2.368319 0.634 0.253 2.530932e-162       0
ENSG00000304278 2.961324e-163   4.388264 0.277 0.027 1.414713e-158       0
NAV2            1.914969e-157   1.089004 0.958 0.894 9.148382e-153       0
TMTC2           5.414732e-157   2.314413 0.730 0.392 2.586780e-152       0
TNC             7.635786e-155   2.255025 0.736 0.405 3.647844e-150       0
FN1             1.502225e-151   3.976176 0.368 0.072 7.176581e-147       0
F3              6.836960e-151   2.291800 0.610 0.245 3.266221e-146       0
ETV6            1.957076e-150   1.908684 0.746 0.429 9.349541e-146       0
GNA14           6.091452e-147   2.893224 0.529 0.181 2.910069e-142       0
GFRA2           2.364266e-146   3.444080 0.313 0.047 1.129481e-141       0
GFAP            1.338196e-144   1.119851 0.940 0.784 6.392966e-140       0
PMP2            9.984503e-141   2.277491 0.628 0.287 4.769896e-136       0
CPNE8           2.382086e-139   2.434396 0.549 0.205 1.137994e-134       0
                           gene
MACF1                     MACF1
TPST1                     TPST1
ARHGEF3                 ARHGEF3
CD44                       CD44
CHI3L1                   CHI3L1
COLEC12                 COLEC12
SULF1                     SULF1
ENSG00000297939 ENSG00000297939
SLC44A3-AS1         SLC44A3-AS1
ENSG00000228408 ENSG00000228408
DST                         DST
ACTN1                     ACTN1
SAMD4A                   SAMD4A
CRISPLD1               CRISPLD1
MAP3K14                 MAP3K14
SLC39A14               SLC39A14
ZFYVE28                 ZFYVE28
ANO6                       ANO6
ENSG00000304278 ENSG00000304278
NAV2                       NAV2
TMTC2                     TMTC2
TNC                         TNC
FN1                         FN1
F3                           F3
ETV6                       ETV6
GNA14                     GNA14
GFRA2                     GFRA2
GFAP                       GFAP
PMP2                       PMP2
CPNE8                     CPNE8
top_astro_cluster_markers <- astro_cluster_markers %>%
  group_by(cluster) %>%
  slice_min(order_by = p_val_adj, n = 20, with_ties = FALSE) %>%
  ungroup()

top_astro_cluster_markers
# A tibble: 240 × 7
       p_val avg_log2FC pct.1 pct.2 p_val_adj cluster gene           
       <dbl>      <dbl> <dbl> <dbl>     <dbl> <fct>   <chr>          
 1 8.38e-304       1.45 0.991 0.932 4.00e-299 0       MACF1          
 2 2.64e-292       2.64 0.822 0.318 1.26e-287 0       TPST1          
 3 3.70e-271       2.86 0.724 0.223 1.77e-266 0       ARHGEF3        
 4 1.47e-265       1.97 0.924 0.519 7.04e-261 0       CD44           
 5 1.56e-233       2.73 0.68  0.209 7.47e-229 0       CHI3L1         
 6 2.77e-230       2.61 0.775 0.342 1.32e-225 0       COLEC12        
 7 9.54e-214       3.71 0.434 0.066 4.56e-209 0       SULF1          
 8 7.03e-212       3.09 0.488 0.09  3.36e-207 0       ENSG00000297939
 9 8.74e-209       2.63 0.685 0.251 4.18e-204 0       SLC44A3-AS1    
10 1.26e-207       3.07 0.579 0.156 6.01e-203 0       ENSG00000228408
# ℹ 230 more rows

6 Step 12.5: Identify lncRNA Candidates

We define lncRNA candidates using gene symbols and available gene annotation.

This step uses two complementary approaches:

1. Symbol-based detection for common lncRNA-style names
2. AnnotationDbi / org.Hs.eg.db annotation where available
lncRNA_symbol_pattern <- paste(
  c(
    "^LINC",
    "-AS[0-9]*$",
    "^AC[0-9]",
    "^AL[0-9]",
    "^AP[0-9]",
    "^MIR[0-9].*HG$",
    "^SNHG",
    "^NEAT1$",
    "^MALAT1$",
    "^XIST$",
    "^KCNQ1OT1$",
    "^MEG3$",
    "^H19$"
  ),
  collapse = "|"
)

lncRNA_symbol_pattern
[1] "^LINC|-AS[0-9]*$|^AC[0-9]|^AL[0-9]|^AP[0-9]|^MIR[0-9].*HG$|^SNHG|^NEAT1$|^MALAT1$|^XIST$|^KCNQ1OT1$|^MEG3$|^H19$"
add_lncRNA_symbol_flag <- function(de_table) {
  de_table %>%
    mutate(
      lncRNA_symbol_like = str_detect(
        gene,
        regex(lncRNA_symbol_pattern, ignore_case = FALSE)
      )
    )
}

astro_reactive_vs_homeostatic_DE <- add_lncRNA_symbol_flag(astro_reactive_vs_homeostatic_DE)
astro_PD_vs_C_DE <- add_lncRNA_symbol_flag(astro_PD_vs_C_DE)
astro_cluster_markers <- add_lncRNA_symbol_flag(astro_cluster_markers)

7 Step 12.6: Add Gene Annotation for Ensembl IDs

If row names are gene symbols, this step adds available Entrez/Ensembl annotation from org.Hs.eg.db.

If some genes are already Ensembl IDs, this step also tries to map them to symbols.

all_genes <- unique(c(
  astro_reactive_vs_homeostatic_DE$gene,
  astro_PD_vs_C_DE$gene,
  astro_cluster_markers$gene
))

symbol_genes <- all_genes[!str_detect(all_genes, "^ENSG")]
ensembl_like_genes <- all_genes[str_detect(all_genes, "^ENSG")]

if (length(symbol_genes) > 0) {
  symbol_annotation <- AnnotationDbi::select(
    org.Hs.eg.db,
    keys = symbol_genes,
    keytype = "SYMBOL",
    columns = c("SYMBOL", "ENTREZID", "ENSEMBL", "GENENAME")
  ) %>%
    as_tibble() %>%
    distinct(SYMBOL, .keep_all = TRUE) %>%
    mutate(gene = SYMBOL) %>%
    dplyr::select(gene, SYMBOL, ENTREZID, ENSEMBL, GENENAME)
} else {
  symbol_annotation <- tibble(
    gene = character(),
    SYMBOL = character(),
    ENTREZID = character(),
    ENSEMBL = character(),
    GENENAME = character()
  )
}

if (length(ensembl_like_genes) > 0) {
  ensembl_annotation <- AnnotationDbi::select(
    org.Hs.eg.db,
    keys = ensembl_like_genes,
    keytype = "ENSEMBL",
    columns = c("SYMBOL", "ENTREZID", "ENSEMBL", "GENENAME")
  ) %>%
    as_tibble() %>%
    distinct(ENSEMBL, .keep_all = TRUE) %>%
    mutate(gene = ENSEMBL) %>%
    dplyr::select(gene, SYMBOL, ENTREZID, ENSEMBL, GENENAME)
} else {
  ensembl_annotation <- tibble(
    gene = character(),
    SYMBOL = character(),
    ENTREZID = character(),
    ENSEMBL = character(),
    GENENAME = character()
  )
}

gene_annotation <- bind_rows(
  symbol_annotation,
  ensembl_annotation
) %>%
  distinct(gene, .keep_all = TRUE)

gene_annotation %>% head(20)
# A tibble: 20 × 5
   gene        SYMBOL      ENTREZID ENSEMBL         GENENAME                    
   <chr>       <chr>       <chr>    <chr>           <chr>                       
 1 MACF1       MACF1       23499    ENSG00000127603 microtubule actin crosslink…
 2 CTNNA3      CTNNA3      29119    ENSG00000183230 catenin alpha 3             
 3 SAMD4A      SAMD4A      23034    ENSG00000020577 sterile alpha motif domain …
 4 CHI3L1      CHI3L1      1116     ENSG00000133048 chitinase 3 like 1          
 5 SHROOM3     SHROOM3     57619    ENSG00000138771 shroom family member 3      
 6 LAMA2       LAMA2       3908     ENSG00000196569 laminin subunit alpha 2     
 7 MDGA2       MDGA2       161357   ENSG00000139915 MAM domain containing glyco…
 8 MALAT1      MALAT1      378938   ENSG00000251562 metastasis associated lung …
 9 SORBS1      SORBS1      10580    ENSG00000095637 sorbin and SH3 domain conta…
10 NEAT1       NEAT1       283131   ENSG00000245532 nuclear paraspeckle assembl…
11 SLC14A1     SLC14A1     6563     ENSG00000141469 solute carrier family 14 me…
12 MIR3171HG.1 MIR3171HG.1 <NA>     <NA>            <NA>                        
13 SPARCL1     SPARCL1     8404     ENSG00000152583 SPARC like 1                
14 MEIS2       MEIS2       4212     ENSG00000134138 Meis homeobox 2             
15 TMTC2       TMTC2       160335   ENSG00000179104 transmembrane O-mannosyltra…
16 PRKCA       PRKCA       5578     ENSG00000154229 protein kinase C alpha      
17 NTRK2       NTRK2       4915     ENSG00000148053 neurotrophic receptor tyros…
18 SLC4A4      SLC4A4      8671     ENSG00000080493 solute carrier family 4 mem…
19 HSPH1       HSPH1       10808    ENSG00000120694 heat shock protein family H…
20 CNTN1       CNTN1       1272     ENSG00000018236 contactin 1                 
annotate_de_table <- function(de_table) {
  de_table %>%
    left_join(gene_annotation, by = "gene") %>%
    mutate(
      gene_symbol_for_plot = case_when(
        !is.na(SYMBOL) ~ SYMBOL,
        TRUE ~ gene
      ),
      lncRNA_annotated_like = case_when(
        lncRNA_symbol_like ~ TRUE,
        str_detect(gene_symbol_for_plot, regex(lncRNA_symbol_pattern)) ~ TRUE,
        TRUE ~ FALSE
      )
    )
}

astro_reactive_vs_homeostatic_annotated <- annotate_de_table(astro_reactive_vs_homeostatic_DE)
astro_PD_vs_C_annotated <- annotate_de_table(astro_PD_vs_C_DE)
astro_cluster_markers_annotated <- annotate_de_table(astro_cluster_markers)

8 Step 12.7: Extract Annotated lncRNA Candidates

We extract lncRNA-like candidates from each comparison.

reactive_lncRNA_candidates <- astro_reactive_vs_homeostatic_annotated %>%
  filter(
    lncRNA_annotated_like,
    p_val_adj < p_adj_cutoff,
    abs(avg_log2FC) >= lncRNA_logfc_cutoff
  ) %>%
  arrange(p_val_adj, desc(abs(avg_log2FC)))

PD_lncRNA_candidates <- astro_PD_vs_C_annotated %>%
  filter(
    lncRNA_annotated_like,
    p_val_adj < p_adj_cutoff,
    abs(avg_log2FC) >= lncRNA_logfc_cutoff
  ) %>%
  arrange(p_val_adj, desc(abs(avg_log2FC)))

cluster_lncRNA_candidates <- astro_cluster_markers_annotated %>%
  filter(
    lncRNA_annotated_like,
    p_val_adj < p_adj_cutoff,
    abs(avg_log2FC) >= lncRNA_logfc_cutoff
  ) %>%
  arrange(cluster, p_val_adj, desc(avg_log2FC))

reactive_lncRNA_candidates %>% head(30)
              gene         p_val avg_log2FC pct.1 pct.2     p_val_adj
1           MALAT1 1.576425e-154 -1.0845420 0.999 0.999 7.531054e-150
2            NEAT1 6.735259e-147  1.3745627 0.982 0.973 3.217635e-142
3         MIR9-1HG 2.324876e-101 -1.1546672 0.490 0.805  1.110663e-96
4      SLC44A3-AS1  1.186607e-78  2.1948605 0.508 0.236  5.668776e-74
5         OBI1-AS1  4.877087e-76 -0.7804023 0.778 0.929  2.329931e-71
6         MIR9-2HG  8.063893e-68 -0.9675675 0.465 0.742  3.852364e-63
7        MIR4300HG  1.738300e-56 -1.3761905 0.319 0.567  8.304380e-52
8         POT1-AS1  1.060027e-52 -1.5792964 0.169 0.406  5.064069e-48
9         UFL1-AS1  5.625404e-50 -2.2780168 0.048 0.230  2.687424e-45
10      PARD6G-AS1  6.780393e-48  3.7422278 0.162 0.015  3.239197e-43
11          SNHG14  2.763769e-47 -0.7431429 0.643 0.837  1.320335e-42
12      ZBTB47-AS1  2.382862e-44 -2.3180731 0.055 0.226  1.138365e-39
13       GNG12-AS1  5.376493e-44 -2.1136746 0.064 0.239  2.568512e-39
14       PCDH9-AS2  1.054542e-41 -1.9696666 0.061 0.229  5.037861e-37
15       LINC03122  6.274795e-39 -1.8833119 0.067 0.232  2.997658e-34
16     SLC38A4-AS1  3.089697e-37 -1.0271390 0.162 0.369  1.476041e-32
17       LINC00412  3.122074e-36 -1.6541773 0.063 0.219  1.491509e-31
18       LINC-PINT  4.700455e-34  0.6813181 0.836 0.818  2.245548e-29
19            XIST  8.160380e-34  1.0386112 0.506 0.307  3.898459e-29
20       PTCHD1-AS  1.040683e-33  0.8249788 0.711 0.625  4.971655e-29
21        MIR99AHG  1.379086e-33 -0.3390699 0.807 0.929  6.588306e-29
22       LINC01376  1.428940e-31 -1.5774871 0.076 0.225  6.826476e-27
23        PAX8-AS1  4.718901e-31 -2.4511875 0.019 0.125  2.254361e-26
24       LINC02232  5.067363e-31 -3.5482579 0.010 0.106  2.420831e-26
25        HEY2-AS1  6.328208e-28 -2.6337186 0.021 0.120  3.023175e-23
26 ENSG00000257545  4.963220e-27 -1.5686148 0.095 0.234  2.371079e-22
27        HOXB-AS1  9.671189e-27 -4.5063008 0.003 0.078  4.620217e-22
28        DBX2-AS1  3.096548e-26 -1.7286998 0.061 0.183  1.479314e-21
29      HECTD2-AS1  7.314350e-26 -1.3889513 0.055 0.175  3.494285e-21
30       LMCD1-AS1  1.167732e-25 -0.5235736 0.525 0.708  5.578605e-21
   lncRNA_symbol_like      SYMBOL  ENTREZID         ENSEMBL
1                TRUE      MALAT1    378938 ENSG00000251562
2                TRUE       NEAT1    283131 ENSG00000245532
3                TRUE    MIR9-1HG     10485 ENSG00000125462
4                TRUE SLC44A3-AS1 101928079 ENSG00000293271
5                TRUE    OBI1-AS1 100874222 ENSG00000234377
6                TRUE    MIR9-2HG    645323 ENSG00000245526
7                TRUE   MIR4300HG 101928989 ENSG00000245832
8                TRUE    POT1-AS1    401398 ENSG00000224897
9                TRUE    UFL1-AS1 100861530            <NA>
10               TRUE  PARD6G-AS1 100130522 ENSG00000267270
11               TRUE      SNHG14 104472715            <NA>
12               TRUE  ZBTB47-AS1 101928323            <NA>
13               TRUE   GNG12-AS1 100289178 ENSG00000232284
14               TRUE   PCDH9-AS2 100874064 ENSG00000228842
15               TRUE   LINC03122    285668 ENSG00000178722
16               TRUE SLC38A4-AS1 100288798 ENSG00000257261
17               TRUE   LINC00412 102723332            <NA>
18               TRUE   LINC-PINT    378805 ENSG00000231721
19               TRUE        XIST      7503 ENSG00000229807
20               TRUE   PTCHD1-AS 100873065            <NA>
21               TRUE    MIR99AHG    388815 ENSG00000215386
22               TRUE   LINC01376    400945 ENSG00000236204
23               TRUE    PAX8-AS1    654433 ENSG00000189223
24               TRUE   LINC02232    401134 ENSG00000250125
25               TRUE    HEY2-AS1 105377986 ENSG00000237742
26              FALSE    RFX4-AS1 100287944 ENSG00000257545
27               TRUE    HOXB-AS1 100874362 ENSG00000230148
28               TRUE    DBX2-AS1 120766145            <NA>
29               TRUE  HECTD2-AS1 100188947 ENSG00000289228
30               TRUE   LMCD1-AS1 100288428 ENSG00000227110
                                                         GENENAME
1          metastasis associated lung adenocarcinoma transcript 1
2                       nuclear paraspeckle assembly transcript 1
3                                                MIR9-1 host gene
4                                         SLC44A3 antisense RNA 1
5                                            OBI1 antisense RNA 1
6                                                MIR9-2 host gene
7                                               MIR4300 host gene
8                                            POT1 antisense RNA 1
9                                            UFL1 antisense RNA 1
10                                         PARD6G antisense RNA 1
11                               small nucleolar RNA host gene 14
12                                ZBTB47 and NKTR antisense RNA 1
13                          GNG12, DIRAS3 and WLS antisense RNA 1
14                                          PCDH9 antisense RNA 2
15                    long intergenic non-protein coding RNA 3122
16                                        SLC38A4 antisense RNA 1
17                     long intergenic non-protein coding RNA 412
18 long intergenic non-protein coding RNA, p53 induced transcript
19                                 X inactive specific transcript
20                                  PTCHD1 and PHEX antisense RNA
21                               mir-99a-let-7c cluster host gene
22                    long intergenic non-protein coding RNA 1376
23                                           PAX8 antisense RNA 1
24                    long intergenic non-protein coding RNA 2232
25                                           HEY2 antisense RNA 1
26                                           RFX4 antisense RNA 1
27                                   HOXB cluster antisense RNA 1
28                                           DBX2 antisense RNA 1
29                                         HECTD2 antisense RNA 1
30                                          LMCD1 antisense RNA 1
   gene_symbol_for_plot lncRNA_annotated_like
1                MALAT1                  TRUE
2                 NEAT1                  TRUE
3              MIR9-1HG                  TRUE
4           SLC44A3-AS1                  TRUE
5              OBI1-AS1                  TRUE
6              MIR9-2HG                  TRUE
7             MIR4300HG                  TRUE
8              POT1-AS1                  TRUE
9              UFL1-AS1                  TRUE
10           PARD6G-AS1                  TRUE
11               SNHG14                  TRUE
12           ZBTB47-AS1                  TRUE
13            GNG12-AS1                  TRUE
14            PCDH9-AS2                  TRUE
15            LINC03122                  TRUE
16          SLC38A4-AS1                  TRUE
17            LINC00412                  TRUE
18            LINC-PINT                  TRUE
19                 XIST                  TRUE
20            PTCHD1-AS                  TRUE
21             MIR99AHG                  TRUE
22            LINC01376                  TRUE
23             PAX8-AS1                  TRUE
24            LINC02232                  TRUE
25             HEY2-AS1                  TRUE
26             RFX4-AS1                  TRUE
27             HOXB-AS1                  TRUE
28             DBX2-AS1                  TRUE
29           HECTD2-AS1                  TRUE
30            LMCD1-AS1                  TRUE
PD_lncRNA_candidates %>% head(30)
              gene         p_val avg_log2FC pct.1 pct.2     p_val_adj
1           MALAT1 3.904114e-208 -1.0785343 0.999 0.999 1.865112e-203
2            NEAT1 6.966431e-117  0.8786913 0.978 0.969 3.328073e-112
3             XIST  3.557471e-87  1.2858607 0.563 0.321  1.699511e-82
4         OBI1-AS1  8.957876e-78 -0.6859095 0.753 0.874  4.279446e-73
5         MIR9-1HG  1.668211e-54 -0.6348170 0.559 0.729  7.969543e-50
6      SLC44A3-AS1  1.123083e-53  1.6386193 0.406 0.229  5.365303e-49
7        LINC00609  7.080087e-52  2.2084204 0.325 0.158  3.382370e-47
8        LINC-PINT  7.873246e-47  0.5638433 0.856 0.811  3.761286e-42
9        LINC02232  1.191495e-40 -3.3450042 0.009 0.084  5.692130e-36
10      PARD6G-AS1  6.513569e-39  2.7031355 0.118 0.022  3.111727e-34
11       PCDH9-AS2  4.253215e-38 -1.7008230 0.071 0.185  2.031888e-33
12       LINC02608  1.878389e-37  3.3371588 0.092 0.011  8.973627e-33
13        POT1-AS1  2.435508e-37 -1.1404088 0.208 0.354  1.163515e-32
14        MIR9-2HG  6.986588e-37 -0.5590838 0.541 0.682  3.337703e-32
15          SNHG14  3.191637e-33 -0.5304722 0.684 0.788  1.524741e-28
16        HOXB-AS1  1.901957e-32 -4.0556306 0.005 0.062  9.086220e-28
17        PAX8-AS1  8.063820e-31 -2.0379081 0.023 0.096  3.852329e-26
18        UFL1-AS1  2.535847e-29 -1.4241608 0.100 0.206  1.211450e-24
19       LINC03082  6.022537e-28  1.4480734 0.177 0.075  2.877146e-23
20       GNG12-AS1  1.910602e-27 -1.2630328 0.087 0.185  9.127518e-23
21       LMCD1-AS1  3.354721e-27 -0.4804939 0.553 0.682  1.602651e-22
22       LINC02649  2.582638e-26 -0.4312792 0.374 0.525  1.233804e-21
23       A2ML1-AS1  5.438267e-25 -2.2663428 0.015 0.071  2.598023e-20
24 ENSG00000257545  5.209622e-24 -1.4020254 0.095 0.188  2.488793e-19
25       LINC00499  4.027478e-23 -1.4627475 0.145 0.241  1.924047e-18
26        GBX2-AS1  4.130220e-23 -0.8578170 0.140 0.247  1.973130e-18
27       LINC01748  4.385189e-23 -0.5107564 0.365 0.491  2.094936e-18
28           AP1S2  1.558181e-22  1.2481882 0.215 0.116  7.443896e-18
29       LINC01727  7.708870e-21 -2.1462329 0.022 0.076  3.682758e-16
30      ENTPD1-AS1  8.047007e-21 -0.6912777 0.270 0.382  3.844297e-16
   lncRNA_symbol_like      SYMBOL  ENTREZID         ENSEMBL
1                TRUE      MALAT1    378938 ENSG00000251562
2                TRUE       NEAT1    283131 ENSG00000245532
3                TRUE        XIST      7503 ENSG00000229807
4                TRUE    OBI1-AS1 100874222 ENSG00000234377
5                TRUE    MIR9-1HG     10485 ENSG00000125462
6                TRUE SLC44A3-AS1 101928079 ENSG00000293271
7                TRUE   LINC00609 101101773 ENSG00000257585
8                TRUE   LINC-PINT    378805 ENSG00000231721
9                TRUE   LINC02232    401134 ENSG00000250125
10               TRUE  PARD6G-AS1 100130522 ENSG00000267270
11               TRUE   PCDH9-AS2 100874064 ENSG00000228842
12               TRUE   LINC02608 101929541 ENSG00000226251
13               TRUE    POT1-AS1    401398 ENSG00000224897
14               TRUE    MIR9-2HG    645323 ENSG00000245526
15               TRUE      SNHG14 104472715            <NA>
16               TRUE    HOXB-AS1 100874362 ENSG00000230148
17               TRUE    PAX8-AS1    654433 ENSG00000189223
18               TRUE    UFL1-AS1 100861530            <NA>
19               TRUE   LINC03082 101927646 ENSG00000275830
20               TRUE   GNG12-AS1 100289178 ENSG00000232284
21               TRUE   LMCD1-AS1 100288428 ENSG00000227110
22               TRUE   LINC02649    399715 ENSG00000215244
23               TRUE   A2ML1-AS1 100874108            <NA>
24              FALSE    RFX4-AS1 100287944 ENSG00000257545
25               TRUE   LINC00499 100874047 ENSG00000251372
26               TRUE    GBX2-AS1 121853074 ENSG00000233611
27               TRUE   LINC01748 105378763 ENSG00000226476
28               TRUE       AP1S2      8905 ENSG00000182287
29               TRUE   LINC01727 101929625            <NA>
30               TRUE  ENTPD1-AS1    728558 ENSG00000226688
                                                         GENENAME
1          metastasis associated lung adenocarcinoma transcript 1
2                       nuclear paraspeckle assembly transcript 1
3                                  X inactive specific transcript
4                                            OBI1 antisense RNA 1
5                                                MIR9-1 host gene
6                                         SLC44A3 antisense RNA 1
7                      long intergenic non-protein coding RNA 609
8  long intergenic non-protein coding RNA, p53 induced transcript
9                     long intergenic non-protein coding RNA 2232
10                                         PARD6G antisense RNA 1
11                                          PCDH9 antisense RNA 2
12                    long intergenic non-protein coding RNA 2608
13                                           POT1 antisense RNA 1
14                                               MIR9-2 host gene
15                               small nucleolar RNA host gene 14
16                                   HOXB cluster antisense RNA 1
17                                           PAX8 antisense RNA 1
18                                           UFL1 antisense RNA 1
19                    long intergenic non-protein coding RNA 3082
20                          GNG12, DIRAS3 and WLS antisense RNA 1
21                                          LMCD1 antisense RNA 1
22                    long intergenic non-protein coding RNA 2649
23                                          A2ML1 antisense RNA 1
24                                           RFX4 antisense RNA 1
25                     long intergenic non-protein coding RNA 499
26                                 GBX2 and ASB18 antisense RNA 1
27                    long intergenic non-protein coding RNA 1748
28              adaptor related protein complex 1 subunit sigma 2
29                    long intergenic non-protein coding RNA 1727
30                                         ENTPD1 antisense RNA 1
   gene_symbol_for_plot lncRNA_annotated_like
1                MALAT1                  TRUE
2                 NEAT1                  TRUE
3                  XIST                  TRUE
4              OBI1-AS1                  TRUE
5              MIR9-1HG                  TRUE
6           SLC44A3-AS1                  TRUE
7             LINC00609                  TRUE
8             LINC-PINT                  TRUE
9             LINC02232                  TRUE
10           PARD6G-AS1                  TRUE
11            PCDH9-AS2                  TRUE
12            LINC02608                  TRUE
13             POT1-AS1                  TRUE
14             MIR9-2HG                  TRUE
15               SNHG14                  TRUE
16             HOXB-AS1                  TRUE
17             PAX8-AS1                  TRUE
18             UFL1-AS1                  TRUE
19            LINC03082                  TRUE
20            GNG12-AS1                  TRUE
21            LMCD1-AS1                  TRUE
22            LINC02649                  TRUE
23            A2ML1-AS1                  TRUE
24             RFX4-AS1                  TRUE
25            LINC00499                  TRUE
26             GBX2-AS1                  TRUE
27            LINC01748                  TRUE
28                AP1S2                  TRUE
29            LINC01727                  TRUE
30           ENTPD1-AS1                  TRUE
cluster_lncRNA_candidates %>% head(30)
           p_val avg_log2FC pct.1 pct.2     p_val_adj cluster            gene
1  8.742003e-209  2.6318030 0.685 0.251 4.176317e-204       0     SLC44A3-AS1
2  6.324121e-130  1.1923412 0.826 0.377 3.021222e-125       0            XIST
3   2.512517e-83  2.7566790 0.355 0.117  1.200305e-78       0       BAALC-AS1
4   1.451409e-82  2.7640326 0.279 0.071  6.933817e-78       0 ENSG00000225339
5   3.727745e-74  5.5093739 0.091 0.003  1.780856e-69       0       LINC01141
6   8.762268e-34  3.2402029 0.086 0.015  4.185998e-29       0       LINC02149
7   8.474345e-32  2.2878437 0.156 0.051  4.048449e-27       0          SNHG31
8   1.696937e-31  2.8286122 0.107 0.026  8.106778e-27       0       SOCS2-AS1
9   2.133988e-29  1.5687449 0.284 0.147  1.019470e-24       0           AP1S2
10  1.935949e-26  0.9473323 0.545 0.419  9.248607e-22       0       LINC02649
11  2.016538e-25  1.4668162 0.227 0.106  9.633606e-21       0        MIR646HG
12  4.288853e-24  3.0928547 0.054 0.008  2.048914e-19       0       LINC01507
13  8.100093e-19  0.5715078 0.686 0.620  3.869657e-14       0       PTCHD1-AS
14  4.538572e-12  1.7310517 0.090 0.038  2.168212e-07       0 ENSG00000258926
15  6.267751e-12  2.0678675 0.077 0.030  2.994293e-07       0       LINC01982
16  1.769349e-11  0.8133984 0.403 0.325  8.452712e-07       0      GABPB1-AS1
17  1.689691e-10  1.5084002 0.077 0.032  8.072163e-06       0       LINC00378
18  3.195055e-10  2.0993945 0.061 0.023  1.526374e-05       0       GNA14-AS1
19  4.161150e-09  1.3188744 0.142 0.084  1.987906e-04       0       LINC02930
20  8.626027e-09  1.8119770 0.068 0.030  4.120912e-04       0       SCN1A-AS1
21  2.022796e-08  1.2628007 0.177 0.117  9.663503e-04       0     TSC22D1-AS1
22  1.044957e-07  1.3530253 0.055 0.023  4.992074e-03       0        MIR325HG
23  1.190234e-07  1.4343420 0.111 0.063  5.686105e-03       0      SAMD4A-AS1
24  2.434808e-07  1.0018066 0.093 0.050  1.163181e-02       0       LINC02177
25  2.470816e-07  1.6585276 0.062 0.028  1.180383e-02       0       MMP25-AS1
26  8.992759e-07  1.5792062 0.051 0.022  4.296111e-02       0          SNHG12
27  3.112877e-46  0.8556845 0.968 0.976  1.487115e-41       1           NEAT1
28  5.441906e-32  0.8602506 0.775 0.702  2.599762e-27       1       LINC01088
29  2.977688e-27  2.3731592 0.105 0.026  1.422531e-22       1       LINC00906
30  1.732202e-18  1.1937929 0.341 0.222  8.275247e-14       1       LINC00836
   lncRNA_symbol_like      SYMBOL  ENTREZID         ENSEMBL
1                TRUE SLC44A3-AS1 101928079 ENSG00000293271
2                TRUE        XIST      7503 ENSG00000229807
3                TRUE   BAALC-AS1 100499183            <NA>
4               FALSE  SMIM29-AS1 139281638 ENSG00000225339
5                TRUE   LINC01141    339505            <NA>
6                TRUE   LINC02149 101929454            <NA>
7                TRUE      SNHG31 101928103 ENSG00000229267
8                TRUE   SOCS2-AS1    144481 ENSG00000246985
9                TRUE       AP1S2      8905 ENSG00000182287
10               TRUE   LINC02649    399715 ENSG00000215244
11               TRUE    MIR646HG    284757 ENSG00000228340
12               TRUE   LINC01507 101927477            <NA>
13               TRUE   PTCHD1-AS 100873065            <NA>
14              FALSE   PRKCH-AS2 105370525 ENSG00000258926
15               TRUE   LINC01982 105371830 ENSG00000263317
16               TRUE  GABPB1-AS1 100129387            <NA>
17               TRUE   LINC00378 101926930            <NA>
18               TRUE   GNA14-AS1 101927422 ENSG00000231373
19               TRUE   LINC02930 105378516 ENSG00000274461
20               TRUE   SCN1A-AS1 101929680 ENSG00000236107
21               TRUE TSC22D1-AS1    641467 ENSG00000278156
22               TRUE    MIR325HG 101928469 ENSG00000280870
23               TRUE  SAMD4A-AS1    729451            <NA>
24               TRUE   LINC02177 101927009 ENSG00000261617
25               TRUE   MMP25-AS1 100507419            <NA>
26               TRUE      SNHG12     85028 ENSG00000197989
27               TRUE       NEAT1    283131 ENSG00000245532
28               TRUE   LINC01088 100505875            <NA>
29               TRUE   LINC00906    148145 ENSG00000267339
30               TRUE   LINC00836 101929052 ENSG00000280809
                                            GENENAME gene_symbol_for_plot
1                            SLC44A3 antisense RNA 1          SLC44A3-AS1
2                     X inactive specific transcript                 XIST
3                              BAALC antisense RNA 1            BAALC-AS1
4                             SMIM29 antisense RNA 1           SMIM29-AS1
5        long intergenic non-protein coding RNA 1141            LINC01141
6        long intergenic non-protein coding RNA 2149            LINC02149
7                   small nucleolar RNA host gene 31               SNHG31
8                              SOCS2 antisense RNA 1            SOCS2-AS1
9  adaptor related protein complex 1 subunit sigma 2                AP1S2
10       long intergenic non-protein coding RNA 2649            LINC02649
11                                  MIR646 host gene             MIR646HG
12       long intergenic non-protein coding RNA 1507            LINC01507
13                     PTCHD1 and PHEX antisense RNA            PTCHD1-AS
14                             PRKCH antisense RNA 2            PRKCH-AS2
15       long intergenic non-protein coding RNA 1982            LINC01982
16                            GABPB1 antisense RNA 1           GABPB1-AS1
17        long intergenic non-protein coding RNA 378            LINC00378
18                             GNA14 antisense RNA 1            GNA14-AS1
19       long intergenic non-protein coding RNA 2930            LINC02930
20                   SCN1A and SCN9A antisense RNA 1            SCN1A-AS1
21                           TSC22D1 antisense RNA 1          TSC22D1-AS1
22                                  MIR325 host gene             MIR325HG
23                            SAMD4A antisense RNA 1           SAMD4A-AS1
24       long intergenic non-protein coding RNA 2177            LINC02177
25                             MMP25 antisense RNA 1            MMP25-AS1
26                  small nucleolar RNA host gene 12               SNHG12
27         nuclear paraspeckle assembly transcript 1                NEAT1
28       long intergenic non-protein coding RNA 1088            LINC01088
29        long intergenic non-protein coding RNA 906            LINC00906
30        long intergenic non-protein coding RNA 836            LINC00836
   lncRNA_annotated_like
1                   TRUE
2                   TRUE
3                   TRUE
4                   TRUE
5                   TRUE
6                   TRUE
7                   TRUE
8                   TRUE
9                   TRUE
10                  TRUE
11                  TRUE
12                  TRUE
13                  TRUE
14                  TRUE
15                  TRUE
16                  TRUE
17                  TRUE
18                  TRUE
19                  TRUE
20                  TRUE
21                  TRUE
22                  TRUE
23                  TRUE
24                  TRUE
25                  TRUE
26                  TRUE
27                  TRUE
28                  TRUE
29                  TRUE
30                  TRUE

9 Step 12.8: Prioritize lncRNAs Shared Across Comparisons

The strongest candidates are lncRNAs associated with both the reactive/stress-like astrocyte state and PD status.

priority_astro_lncRNAs <- reactive_lncRNA_candidates %>%
  dplyr::select(
    gene,
    gene_symbol_for_plot,
    avg_log2FC_reactive_vs_homeostatic = avg_log2FC,
    p_val_adj_reactive_vs_homeostatic = p_val_adj,
    pct.1_reactive = pct.1,
    pct.2_homeostatic = pct.2,
    GENENAME
  ) %>%
  inner_join(
    PD_lncRNA_candidates %>%
      dplyr::select(
        gene,
        avg_log2FC_PD_vs_C = avg_log2FC,
        p_val_adj_PD_vs_C = p_val_adj,
        pct.1_PD = pct.1,
        pct.2_C = pct.2
      ),
    by = "gene"
  ) %>%
  mutate(
    same_direction = sign(avg_log2FC_reactive_vs_homeostatic) == sign(avg_log2FC_PD_vs_C),
    priority_score =
      -log10(p_val_adj_reactive_vs_homeostatic + 1e-300) +
      -log10(p_val_adj_PD_vs_C + 1e-300) +
      abs(avg_log2FC_reactive_vs_homeostatic) +
      abs(avg_log2FC_PD_vs_C)
  ) %>%
  arrange(desc(same_direction), desc(priority_score))

priority_astro_lncRNAs
               gene gene_symbol_for_plot avg_log2FC_reactive_vs_homeostatic
1            MALAT1               MALAT1                         -1.0845420
2             NEAT1                NEAT1                          1.3745627
3          MIR9-1HG             MIR9-1HG                         -1.1546672
4          OBI1-AS1             OBI1-AS1                         -0.7804023
5       SLC44A3-AS1          SLC44A3-AS1                          2.1948605
6              XIST                 XIST                          1.0386112
7          MIR9-2HG             MIR9-2HG                         -0.9675675
8        PARD6G-AS1           PARD6G-AS1                          3.7422278
9          POT1-AS1             POT1-AS1                         -1.5792964
10        PCDH9-AS2            PCDH9-AS2                         -1.9696666
11         UFL1-AS1             UFL1-AS1                         -2.2780168
12        LINC-PINT            LINC-PINT                          0.6813181
13           SNHG14               SNHG14                         -0.7431429
14        LINC02232            LINC02232                         -3.5482579
15        GNG12-AS1            GNG12-AS1                         -2.1136746
16        MIR4300HG            MIR4300HG                         -1.3761905
17         HOXB-AS1             HOXB-AS1                         -4.5063008
18         PAX8-AS1             PAX8-AS1                         -2.4511875
19       ZBTB47-AS1           ZBTB47-AS1                         -2.3180731
20        LINC00412            LINC00412                         -1.6541773
21        LINC03122            LINC03122                         -1.8833119
22        A2ML1-AS1            A2ML1-AS1                         -2.8471687
23  ENSG00000257545             RFX4-AS1                         -1.5686148
24        LMCD1-AS1            LMCD1-AS1                         -0.5235736
25        LINC02608            LINC02608                          2.4331917
26        LINC01376            LINC01376                         -1.5774871
27        LINC01727            LINC01727                         -4.1531683
28      SLC38A4-AS1          SLC38A4-AS1                         -1.0271390
29        LINC01748            LINC01748                         -0.5289954
30       HECTD2-AS1           HECTD2-AS1                         -1.3889513
31         HEY2-AS1             HEY2-AS1                         -2.6337186
32        PTCHD1-AS            PTCHD1-AS                          0.8249788
33         LRP4-AS1             LRP4-AS1                         -3.2142539
34        LINC01572            LINC01572                         -1.4602397
35         ANK2-AS1             ANK2-AS1                         -2.6043069
36         PKIA-AS1             PKIA-AS1                         -2.9101779
37         DBX2-AS1             DBX2-AS1                         -1.7286998
38       ENTPD1-AS1           ENTPD1-AS1                         -0.6786507
39         GBX2-AS1             GBX2-AS1                         -0.7910011
40        LINC00173            LINC00173                         -1.2509725
41        RAP2C-AS1            RAP2C-AS1                         -1.7403309
42       RASSF8-AS1           RASSF8-AS1                         -1.0654679
43         TET2-AS1             TET2-AS1                          1.5461079
44         LIFR-AS1             LIFR-AS1                         -2.3646125
45        BAALC-AS1            BAALC-AS1                          1.9699019
46        SOCS2-AS1            SOCS2-AS1                          2.9038008
47            AP1S2                AP1S2                          1.3954165
48       GASK1B-AS1           GASK1B-AS1                         -0.7620764
49        LINC00960            LINC00960                         -1.8085364
50      ATP13A4-AS1          ATP13A4-AS1                         -2.0601332
51        LINC01414            LINC01414                         -2.4219273
52      SLC28A2-AS1          SLC28A2-AS1                         -1.2546195
53        MIR4500HG            MIR4500HG                         -2.4564245
54        LINC00499            LINC00499                         -1.2669032
55       MIDEAS-AS1           MIDEAS-AS1                         -2.1047880
56        SNED1-AS1            SNED1-AS1                         -2.0433184
57        MEF2C-AS1            MEF2C-AS1                         -0.7341850
58       HEXIM2-AS1           HEXIM2-AS1                         -0.9379578
59      ZKSCAN7-AS1          ZKSCAN7-AS1                         -1.1009480
60        LINC03062            LINC03062                         -2.5855973
61       CALCRL-AS1           CALCRL-AS1                         -1.4599570
62        FSIP2-AS1            FSIP2-AS1                         -0.7595069
63         USP3-AS1             USP3-AS1                         -1.7767793
64        LINC00378            LINC00378                          2.1267031
65      NECTIN3-AS1          NECTIN3-AS1                         -2.9074828
66         WEE2-AS1             WEE2-AS1                         -2.3028693
67        PDE7B-AS1            PDE7B-AS1                         -1.1195818
68       ZNF337-AS1           ZNF337-AS1                         -0.9198971
69       MIR219A2HG           MIR219A2HG                         -1.8896088
70        LINC01117            LINC01117                         -1.7541741
71         IPO9-AS1             IPO9-AS1                         -1.3286924
72        LINC02580            LINC02580                         -1.3816355
73         OTX2-AS1             OTX2-AS1                          2.9017871
74         LIX1-AS1             LIX1-AS1                         -1.2574453
75      SYNPO2L-AS1          SYNPO2L-AS1                         -1.2648196
76  ENSG00000303699          ANKRD17-AS1                         -1.5284179
77        LINC00240            LINC00240                         -1.5438983
78          BDNF-AS              BDNF-AS                         -0.7941867
79        LINC00862            LINC00862                          1.5586712
80        BCL10-AS1            BCL10-AS1                         -2.1383304
81        NR2F1-AS1            NR2F1-AS1                         -0.5012591
82        LINC02614            LINC02614                         -0.9224436
83         PDK4-AS1             PDK4-AS1                         -1.0305083
84       TMEM72-AS1           TMEM72-AS1                         -1.0091249
85       UBE2D3-AS1           UBE2D3-AS1                          1.6360227
86        EIF1B-AS1            EIF1B-AS1                         -0.5186210
87        DAAM2-AS1            DAAM2-AS1                         -1.7214142
88         MIR9-3HG             MIR9-3HG                         -1.0149620
89        LSAMP-AS1            LSAMP-AS1                         -1.4696069
90  ENSG00000225339           SMIM29-AS1                          1.5609970
91        LINC00472            LINC00472                          0.9223688
92        ITGA9-AS1            ITGA9-AS1                         -0.5956222
93        ZFPM2-AS1            ZFPM2-AS1                         -1.9082963
94        LINC00467            LINC00467                         -1.3848838
95        LINC00844            LINC00844                         -0.8087702
96        ZFHX3-AS1            ZFHX3-AS1                         -1.6656193
97  ENSG00000287158            LINC03214                         -1.4928563
98        LINC01994            LINC01994                         -0.8380970
99  ENSG00000258162           PPFIA2-AS2                         -1.5247043
100       MIR3659HG            MIR3659HG                          1.5856483
101     JAKMIP2-AS1          JAKMIP2-AS1                         -1.3164264
102        RHOQ-AS1             RHOQ-AS1                         -1.7468010
103       LINC02796            LINC02796                         -0.6065784
104       LINC02934            LINC02934                         -0.4288249
105       PRKCA-AS1            PRKCA-AS1                         -0.8366604
106       DPP10-AS3            DPP10-AS3                         -1.3361915
107       RBMS3-AS3            RBMS3-AS3                         -1.5543115
108           AP1AR                AP1AR                          1.4325981
109       LINC03051            LINC03051                          0.4705735
110       LINC02895            LINC02895                         -0.6752028
    p_val_adj_reactive_vs_homeostatic pct.1_reactive pct.2_homeostatic
1                       7.531054e-150          0.999             0.999
2                       3.217635e-142          0.982             0.973
3                        1.110663e-96          0.490             0.805
4                        2.329931e-71          0.778             0.929
5                        5.668776e-74          0.508             0.236
6                        3.898459e-29          0.506             0.307
7                        3.852364e-63          0.465             0.742
8                        3.239197e-43          0.162             0.015
9                        5.064069e-48          0.169             0.406
10                       5.037861e-37          0.061             0.229
11                       2.687424e-45          0.048             0.230
12                       2.245548e-29          0.836             0.818
13                       1.320335e-42          0.643             0.837
14                       2.420831e-26          0.010             0.106
15                       2.568512e-39          0.064             0.239
16                       8.304380e-52          0.319             0.567
17                       4.620217e-22          0.003             0.078
18                       2.254361e-26          0.019             0.125
19                       1.138365e-39          0.055             0.226
20                       1.491509e-31          0.063             0.219
21                       2.997658e-34          0.067             0.232
22                       6.510260e-20          0.013             0.095
23                       2.371079e-22          0.095             0.234
24                       5.578605e-21          0.525             0.708
25                       1.251068e-05          0.051             0.012
26                       6.826476e-27          0.076             0.225
27                       3.420788e-20          0.006             0.080
28                       1.476041e-32          0.162             0.369
29                       2.343689e-19          0.359             0.552
30                       3.494285e-21          0.055             0.175
31                       3.023175e-23          0.021             0.120
32                       4.971655e-29          0.711             0.625
33                       3.112172e-17          0.007             0.075
34                       3.222778e-19          0.052             0.163
35                       9.870437e-17          0.020             0.099
36                       2.104432e-19          0.016             0.100
37                       1.479314e-21          0.061             0.183
38                       3.463486e-15          0.254             0.408
39                       1.372355e-12          0.152             0.279
40                       1.277363e-19          0.060             0.178
41                       1.698291e-16          0.031             0.119
42                       9.932642e-18          0.104             0.234
43                       2.567255e-11          0.177             0.083
44                       8.193928e-18          0.023             0.109
45                       4.533165e-17          0.247             0.126
46                       8.319323e-10          0.072             0.016
47                       1.104988e-07          0.207             0.123
48                       1.490042e-10          0.150             0.263
49                       1.165603e-13          0.034             0.115
50                       8.703296e-12          0.026             0.094
51                       5.590474e-10          0.014             0.068
52                       4.050410e-15          0.048             0.144
53                       1.642947e-11          0.014             0.073
54                       2.308796e-04          0.187             0.254
55                       6.921594e-11          0.011             0.065
56                       4.400615e-11          0.017             0.078
57                       3.655561e-19          0.241             0.413
58                       3.007789e-14          0.073             0.181
59                       4.258019e-16          0.064             0.173
60                       2.123997e-11          0.012             0.068
61                       2.003744e-08          0.033             0.096
62                       4.434546e-15          0.169             0.312
63                       1.663182e-11          0.017             0.080
64                       1.042241e-05          0.054             0.013
65                       1.767182e-13          0.012             0.075
66                       2.808869e-11          0.015             0.074
67                       8.706967e-10          0.053             0.132
68                       1.408456e-11          0.059             0.150
69                       2.947967e-06          0.020             0.067
70                       3.181638e-07          0.019             0.068
71                       5.277608e-12          0.037             0.116
72                       6.212818e-12          0.045             0.127
73                       2.448193e-09          0.081             0.023
74                       1.435700e-11          0.065             0.156
75                       3.363365e-13          0.041             0.127
76                       5.706931e-07          0.041             0.103
77                       4.163614e-07          0.021             0.072
78                       3.282729e-10          0.121             0.228
79                       1.107380e-06          0.091             0.034
80                       4.561151e-09          0.019             0.074
81                       6.773300e-12          0.330             0.475
82                       4.979919e-12          0.129             0.242
83                       2.349247e-11          0.067             0.158
84                       1.666430e-11          0.080             0.178
85                       1.691957e-06          0.112             0.049
86                       2.362974e-09          0.236             0.362
87                       1.194161e-09          0.029             0.093
88                       1.303006e-09          0.081             0.171
89                       8.009277e-07          0.032             0.089
90                       1.352302e-08          0.179             0.096
91                       8.015808e-06          0.458             0.421
92                       5.918311e-11          0.154             0.275
93                       1.982926e-05          0.019             0.063
94                       1.892471e-07          0.031             0.089
95                       1.232605e-09          0.101             0.200
96                       1.276877e-07          0.028             0.085
97                       3.588883e-07          0.037             0.098
98                       1.670540e-05          0.072             0.142
99                       7.016993e-05          0.024             0.070
100                      5.929153e-04          0.087             0.039
101                      1.995836e-04          0.031             0.078
102                      3.953795e-04          0.024             0.066
103                      2.010877e-06          0.120             0.209
104                      3.256543e-07          0.264             0.388
105                      7.953078e-03          0.070             0.125
106                      4.968059e-05          0.025             0.071
107                      6.315568e-04          0.024             0.065
108                      2.143264e-02          0.074             0.034
109                      6.502419e-05          0.736             0.746
110                      6.031012e-03          0.073             0.130
                                                           GENENAME
1            metastasis associated lung adenocarcinoma transcript 1
2                         nuclear paraspeckle assembly transcript 1
3                                                  MIR9-1 host gene
4                                              OBI1 antisense RNA 1
5                                           SLC44A3 antisense RNA 1
6                                    X inactive specific transcript
7                                                  MIR9-2 host gene
8                                            PARD6G antisense RNA 1
9                                              POT1 antisense RNA 1
10                                            PCDH9 antisense RNA 2
11                                             UFL1 antisense RNA 1
12   long intergenic non-protein coding RNA, p53 induced transcript
13                                 small nucleolar RNA host gene 14
14                      long intergenic non-protein coding RNA 2232
15                            GNG12, DIRAS3 and WLS antisense RNA 1
16                                                MIR4300 host gene
17                                     HOXB cluster antisense RNA 1
18                                             PAX8 antisense RNA 1
19                                  ZBTB47 and NKTR antisense RNA 1
20                       long intergenic non-protein coding RNA 412
21                      long intergenic non-protein coding RNA 3122
22                                            A2ML1 antisense RNA 1
23                                             RFX4 antisense RNA 1
24                                            LMCD1 antisense RNA 1
25                      long intergenic non-protein coding RNA 2608
26                      long intergenic non-protein coding RNA 1376
27                      long intergenic non-protein coding RNA 1727
28                                          SLC38A4 antisense RNA 1
29                      long intergenic non-protein coding RNA 1748
30                                           HECTD2 antisense RNA 1
31                                             HEY2 antisense RNA 1
32                                    PTCHD1 and PHEX antisense RNA
33                                             LRP4 antisense RNA 1
34                      long intergenic non-protein coding RNA 1572
35                                             ANK2 antisense RNA 1
36                                             PKIA antisense RNA 1
37                                             DBX2 antisense RNA 1
38                                           ENTPD1 antisense RNA 1
39                                   GBX2 and ASB18 antisense RNA 1
40                       long intergenic non-protein coding RNA 173
41                                            RAP2C antisense RNA 1
42                                           RASSF8 antisense RNA 1
43                                             TET2 antisense RNA 1
44                                             LIFR antisense RNA 1
45                                            BAALC antisense RNA 1
46                                            SOCS2 antisense RNA 1
47                adaptor related protein complex 1 subunit sigma 2
48                                           GASK1B antisense RNA 1
49                       long intergenic non-protein coding RNA 960
50                                          ATP13A4 antisense RNA 1
51                      long intergenic non-protein coding RNA 1414
52                                          SLC28A2 antisense RNA 1
53                                                MIR4500 host gene
54                       long intergenic non-protein coding RNA 499
55                                           MIDEAS antisense RNA 1
56                                            SNED1 antisense RNA 1
57                                            MEF2C antisense RNA 1
58                                           HEXIM2 antisense RNA 1
59                              ZKSCAN7 ZNF cluster antisense RNA 1
60                      long intergenic non-protein coding RNA 3062
61                                  CALCRL and TFPI antisense RNA 1
62                                            FSIP2 antisense RNA 1
63                                             USP3 antisense RNA 1
64                       long intergenic non-protein coding RNA 378
65                                          NECTIN3 antisense RNA 1
66                                             WEE2 antisense RNA 1
67                                            PDE7B antisense RNA 1
68                                           ZNF337 antisense RNA 1
69                                               MIR219A2 host gene
70                      long intergenic non-protein coding RNA 1117
71                                             IPO9 antisense RNA 1
72                      long intergenic non-protein coding RNA 2580
73                                             OTX2 antisense RNA 1
74                                   LIX1 and RIOK2 antisense RNA 1
75                                          SYNPO2L antisense RNA 1
76                                           ANKRD17 antisense RNA1
77                       long intergenic non-protein coding RNA 240
78                                               BDNF antisense RNA
79                       long intergenic non-protein coding RNA 862
80                                            BCL10 antisense RNA 1
81                                 NR2F1 regulatory antisense RNA 1
82                      long intergenic non-protein coding RNA 2614
83                                             PDK4 antisense RNA 1
84                                           TMEM72 antisense RNA 1
85                                           UBE2D3 antisense RNA 1
86                                            EIF1B antisense RNA 1
87                                            DAAM2 antisense RNA 1
88                                                 MIR9-3 host gene
89                                            LSAMP antisense RNA 1
90                                           SMIM29 antisense RNA 1
91                       long intergenic non-protein coding RNA 472
92                                            ITGA9 antisense RNA 1
93                                            ZFPM2 antisense RNA 1
94                       long intergenic non-protein coding RNA 467
95                       long intergenic non-protein coding RNA 844
96                                            ZFHX3 antisense RNA 1
97                      long intergenic non-protein coding RNA 3214
98                      long intergenic non-protein coding RNA 1994
99                                           PPFIA2 antisense RNA 2
100                                               MIR3659 host gene
101                                         JAKMIP2 antisense RNA 1
102                                            RHOQ antisense RNA 1
103                     long intergenic non-protein coding RNA 2796
104                     long intergenic non-protein coding RNA 2934
105                                           PRKCA antisense RNA 1
106                                           DPP10 antisense RNA 3
107                                           RBMS3 antisense RNA 3
108 adaptor related protein complex 1 associated regulatory protein
109                     long intergenic non-protein coding RNA 3051
110                     long intergenic non-protein coding RNA 2895
    avg_log2FC_PD_vs_C p_val_adj_PD_vs_C pct.1_PD pct.2_C same_direction
1           -1.0785343     1.865112e-203    0.999   0.999           TRUE
2            0.8786913     3.328073e-112    0.978   0.969           TRUE
3           -0.6348170      7.969543e-50    0.559   0.729           TRUE
4           -0.6859095      4.279446e-73    0.753   0.874           TRUE
5            1.6386193      5.365303e-49    0.406   0.229           TRUE
6            1.2858607      1.699511e-82    0.563   0.321           TRUE
7           -0.5590838      3.337703e-32    0.541   0.682           TRUE
8            2.7031355      3.111727e-34    0.118   0.022           TRUE
9           -1.1404088      1.163515e-32    0.208   0.354           TRUE
10          -1.7008230      2.031888e-33    0.071   0.185           TRUE
11          -1.4241608      1.211450e-24    0.100   0.206           TRUE
12           0.5638433      3.761286e-42    0.856   0.811           TRUE
13          -0.5304722      1.524741e-28    0.684   0.788           TRUE
14          -3.3450042      5.692130e-36    0.009   0.084           TRUE
15          -1.2630328      9.127518e-23    0.087   0.185           TRUE
16          -0.3826847      3.402057e-06    0.402   0.481           TRUE
17          -4.0556306      9.086220e-28    0.005   0.062           TRUE
18          -2.0379081      3.852329e-26    0.023   0.096           TRUE
19          -1.1977744      1.730185e-13    0.121   0.203           TRUE
20          -1.0041436      1.908970e-14    0.108   0.192           TRUE
21          -0.7953887      2.527353e-11    0.132   0.213           TRUE
22          -2.2663428      2.598023e-20    0.015   0.071           TRUE
23          -1.4020254      2.488793e-19    0.095   0.188           TRUE
24          -0.4804939      1.602651e-22    0.553   0.682           TRUE
25           3.3371588      8.973627e-33    0.092   0.011           TRUE
26          -0.9334588      2.621275e-13    0.120   0.205           TRUE
27          -2.1462329      3.682758e-16    0.022   0.076           TRUE
28          -0.5356175      6.442011e-08    0.227   0.311           TRUE
29          -0.5107564      2.094936e-18    0.365   0.491           TRUE
30          -1.0857890      2.722708e-14    0.077   0.153           TRUE
31          -1.4310725      3.328734e-10    0.044   0.098           TRUE
32           0.3840640      3.855021e-07    0.652   0.606           TRUE
33          -2.4653985      2.536101e-13    0.014   0.057           TRUE
34          -1.2175268      7.039090e-14    0.066   0.137           TRUE
35          -2.0617487      7.873702e-13    0.027   0.077           TRUE
36          -1.7806304      5.116827e-10    0.032   0.080           TRUE
37          -1.0621147      9.223505e-10    0.082   0.147           TRUE
38          -0.6912777      3.844297e-16    0.270   0.382           TRUE
39          -0.8578170      1.973130e-18    0.140   0.247           TRUE
40          -0.8934571      7.264393e-11    0.069   0.135           TRUE
41          -1.2403898      7.949843e-12    0.053   0.114           TRUE
42          -0.8599095      4.999190e-10    0.125   0.200           TRUE
43           1.1735145      2.246857e-15    0.173   0.086           TRUE
44          -1.3251389      9.795100e-08    0.051   0.100           TRUE
45           1.2507027      1.965654e-08    0.190   0.119           TRUE
46           2.5328871      3.205104e-13    0.061   0.014           TRUE
47           1.2481882      7.443896e-18    0.215   0.116           TRUE
48          -0.9390244      7.411156e-16    0.138   0.233           TRUE
49          -1.4989419      6.298500e-10    0.038   0.087           TRUE
50          -1.8837620      6.789299e-11    0.026   0.072           TRUE
51          -2.2000756      1.084779e-11    0.019   0.062           TRUE
52          -1.0324631      2.030816e-08    0.072   0.131           TRUE
53          -1.8622106      1.004560e-09    0.020   0.060           TRUE
54          -1.4627475      1.924047e-18    0.145   0.241           TRUE
55          -1.7928889      3.561712e-10    0.014   0.051           TRUE
56          -1.6182813      8.616760e-10    0.022   0.064           TRUE
57          -0.3033979      1.693342e-03    0.323   0.398           TRUE
58          -0.6881924      1.129753e-07    0.100   0.164           TRUE
59          -0.7325966      1.846123e-05    0.094   0.149           TRUE
60          -1.7315357      2.687633e-07    0.019   0.054           TRUE
61          -1.6336982      2.237494e-11    0.033   0.083           TRUE
62          -0.5366656      4.912220e-06    0.207   0.278           TRUE
63          -1.4075043      1.038754e-07    0.026   0.066           TRUE
64           1.9176396      1.354137e-12    0.061   0.015           TRUE
65          -1.5334647      2.083619e-04    0.028   0.061           TRUE
66          -1.5212145      3.770219e-07    0.023   0.060           TRUE
67          -1.2077131      1.396314e-09    0.048   0.101           TRUE
68          -0.8570729      8.650509e-08    0.076   0.134           TRUE
69          -1.9527912      1.067118e-10    0.024   0.068           TRUE
70          -1.6799383      5.811928e-10    0.015   0.053           TRUE
71          -1.0080648      6.225659e-05    0.050   0.092           TRUE
72          -0.9498066      7.167198e-05    0.066   0.111           TRUE
73           1.4726849      2.411075e-05    0.066   0.029           TRUE
74          -0.8830735      3.146696e-05    0.087   0.139           TRUE
75          -0.8009231      1.895176e-03    0.064   0.106           TRUE
76          -1.5731402      1.310611e-08    0.032   0.076           TRUE
77          -1.6760204      3.061914e-08    0.026   0.066           TRUE
78          -0.6863693      9.725967e-07    0.139   0.206           TRUE
79           1.0898264      6.905976e-09    0.096   0.043           TRUE
80          -1.5546684      4.077856e-05    0.027   0.061           TRUE
81          -0.3255635      8.698939e-05    0.385   0.458           TRUE
82          -0.6547661      9.459607e-04    0.168   0.223           TRUE
83          -0.7743301      2.033560e-03    0.090   0.135           TRUE
84          -0.5999107      2.813741e-03    0.114   0.164           TRUE
85           1.1927386      9.762336e-07    0.100   0.051           TRUE
86          -0.4332346      8.009286e-05    0.293   0.360           TRUE
87          -1.2034929      1.563902e-02    0.039   0.069           TRUE
88          -0.7669306      1.351762e-03    0.100   0.148           TRUE
89          -1.3777549      3.701280e-05    0.040   0.078           TRUE
90           1.1038821      1.475434e-03    0.128   0.082           TRUE
91           0.5760819      3.018961e-07    0.482   0.420           TRUE
92          -0.3769998      1.344479e-02    0.211   0.268           TRUE
93          -1.5876122      5.350543e-05    0.020   0.051           TRUE
94          -1.0521023      1.956912e-03    0.043   0.079           TRUE
95          -0.5279199      4.012277e-02    0.120   0.166           TRUE
96          -1.1075559      1.683174e-02    0.042   0.074           TRUE
97          -1.1679230      8.163301e-03    0.047   0.081           TRUE
98          -0.8802699      2.367852e-05    0.072   0.121           TRUE
99          -1.3962449      2.191334e-04    0.027   0.060           TRUE
100          1.1126372      1.843104e-05    0.090   0.046           TRUE
101         -1.3442059      3.803868e-04    0.029   0.061           TRUE
102         -1.6176164      1.415566e-03    0.026   0.055           TRUE
103         -0.5799762      4.504183e-03    0.128   0.179           TRUE
104         -0.3467941      1.448512e-02    0.300   0.366           TRUE
105         -1.0205611      8.579029e-06    0.054   0.100           TRUE
106         -1.1193793      9.337767e-03    0.026   0.054           TRUE
107         -1.3326728      2.169708e-03    0.024   0.052           TRUE
108          1.0889663      8.213554e-04    0.070   0.034           TRUE
109          0.2826169      5.626406e-03    0.730   0.721           TRUE
110         -0.8321417      9.758364e-04    0.074   0.118           TRUE
    priority_score
1       354.015516
2       255.223524
3       146.842468
4       144.467581
5       125.350396
6       112.503255
7        95.417476
8        82.441924
9        81.949433
10       72.660344
11       72.189536
12       71.318503
13       70.969735
14       67.754023
15       64.006673
16       58.307826
17       56.938886
18       55.550349
19       55.221473
20       47.203896
21       46.799253
22       43.885270
23       43.199705
24       43.052703
25       42.720101
26       41.258237
27       41.199102
28       40.584637
29       37.348681
30       36.496381
31       36.062049
32       35.926515
33       34.782422
34       34.322020
35       32.775540
36       32.658673
37       32.655858
38       31.245598
39       31.216196
40       31.176916
41       29.850350
42       28.229413
43       27.958578
44       27.785250
45       27.270696
46       27.010758
47       26.728447
48       26.658016
49       25.441690
50       25.172387
51       24.839213
52       24.371913
53       24.101035
54       24.082050
55       23.505812
56       23.082742
57       22.245884
58       22.094919
59       21.938076
60       21.560609
61       21.442051
62       20.958046
63       20.946831
64       20.894712
65       20.874848
66       20.799186
67       20.242445
68       19.691185
69       19.344665
70       19.167141
71       17.820135
72       17.682804
73       17.603416
74       17.485600
75       17.261319
76       17.227682
77       17.114455
78       16.976388
79       16.764976
80       16.423492
81       16.056556
82       15.904114
83       15.125653
84       14.937964
85       14.610818
86       13.674803
87       13.653635
88       13.536046
89       13.375417
90       13.364886
91       13.114646
92       13.071870
93       12.470204
94       11.868386
95       11.642475
96       11.440897
97       11.193954
98       11.121155
99       10.734090
100      10.659743
101       9.780282
102       9.616473
103       9.229553
104       9.101940
105       9.023248
106       8.789141
107       8.750171
108       7.275958
109       7.189884
110       6.737577
cluster_lncRNA_support <- cluster_lncRNA_candidates %>%
  group_by(gene) %>%
  summarise(
    cluster_support = paste(sort(unique(cluster)), collapse = ";"),
    max_cluster_log2FC = max(avg_log2FC, na.rm = TRUE),
    min_cluster_p_val_adj = min(p_val_adj, na.rm = TRUE),
    .groups = "drop"
  )

priority_astro_lncRNAs <- priority_astro_lncRNAs %>%
  left_join(cluster_lncRNA_support, by = "gene") %>%
  arrange(desc(same_direction), desc(priority_score))

priority_astro_lncRNAs
               gene gene_symbol_for_plot avg_log2FC_reactive_vs_homeostatic
1            MALAT1               MALAT1                         -1.0845420
2             NEAT1                NEAT1                          1.3745627
3          MIR9-1HG             MIR9-1HG                         -1.1546672
4          OBI1-AS1             OBI1-AS1                         -0.7804023
5       SLC44A3-AS1          SLC44A3-AS1                          2.1948605
6              XIST                 XIST                          1.0386112
7          MIR9-2HG             MIR9-2HG                         -0.9675675
8        PARD6G-AS1           PARD6G-AS1                          3.7422278
9          POT1-AS1             POT1-AS1                         -1.5792964
10        PCDH9-AS2            PCDH9-AS2                         -1.9696666
11         UFL1-AS1             UFL1-AS1                         -2.2780168
12        LINC-PINT            LINC-PINT                          0.6813181
13           SNHG14               SNHG14                         -0.7431429
14        LINC02232            LINC02232                         -3.5482579
15        GNG12-AS1            GNG12-AS1                         -2.1136746
16        MIR4300HG            MIR4300HG                         -1.3761905
17         HOXB-AS1             HOXB-AS1                         -4.5063008
18         PAX8-AS1             PAX8-AS1                         -2.4511875
19       ZBTB47-AS1           ZBTB47-AS1                         -2.3180731
20        LINC00412            LINC00412                         -1.6541773
21        LINC03122            LINC03122                         -1.8833119
22        A2ML1-AS1            A2ML1-AS1                         -2.8471687
23  ENSG00000257545             RFX4-AS1                         -1.5686148
24        LMCD1-AS1            LMCD1-AS1                         -0.5235736
25        LINC02608            LINC02608                          2.4331917
26        LINC01376            LINC01376                         -1.5774871
27        LINC01727            LINC01727                         -4.1531683
28      SLC38A4-AS1          SLC38A4-AS1                         -1.0271390
29        LINC01748            LINC01748                         -0.5289954
30       HECTD2-AS1           HECTD2-AS1                         -1.3889513
31         HEY2-AS1             HEY2-AS1                         -2.6337186
32        PTCHD1-AS            PTCHD1-AS                          0.8249788
33         LRP4-AS1             LRP4-AS1                         -3.2142539
34        LINC01572            LINC01572                         -1.4602397
35         ANK2-AS1             ANK2-AS1                         -2.6043069
36         PKIA-AS1             PKIA-AS1                         -2.9101779
37         DBX2-AS1             DBX2-AS1                         -1.7286998
38       ENTPD1-AS1           ENTPD1-AS1                         -0.6786507
39         GBX2-AS1             GBX2-AS1                         -0.7910011
40        LINC00173            LINC00173                         -1.2509725
41        RAP2C-AS1            RAP2C-AS1                         -1.7403309
42       RASSF8-AS1           RASSF8-AS1                         -1.0654679
43         TET2-AS1             TET2-AS1                          1.5461079
44         LIFR-AS1             LIFR-AS1                         -2.3646125
45        BAALC-AS1            BAALC-AS1                          1.9699019
46        SOCS2-AS1            SOCS2-AS1                          2.9038008
47            AP1S2                AP1S2                          1.3954165
48       GASK1B-AS1           GASK1B-AS1                         -0.7620764
49        LINC00960            LINC00960                         -1.8085364
50      ATP13A4-AS1          ATP13A4-AS1                         -2.0601332
51        LINC01414            LINC01414                         -2.4219273
52      SLC28A2-AS1          SLC28A2-AS1                         -1.2546195
53        MIR4500HG            MIR4500HG                         -2.4564245
54        LINC00499            LINC00499                         -1.2669032
55       MIDEAS-AS1           MIDEAS-AS1                         -2.1047880
56        SNED1-AS1            SNED1-AS1                         -2.0433184
57        MEF2C-AS1            MEF2C-AS1                         -0.7341850
58       HEXIM2-AS1           HEXIM2-AS1                         -0.9379578
59      ZKSCAN7-AS1          ZKSCAN7-AS1                         -1.1009480
60        LINC03062            LINC03062                         -2.5855973
61       CALCRL-AS1           CALCRL-AS1                         -1.4599570
62        FSIP2-AS1            FSIP2-AS1                         -0.7595069
63         USP3-AS1             USP3-AS1                         -1.7767793
64        LINC00378            LINC00378                          2.1267031
65      NECTIN3-AS1          NECTIN3-AS1                         -2.9074828
66         WEE2-AS1             WEE2-AS1                         -2.3028693
67        PDE7B-AS1            PDE7B-AS1                         -1.1195818
68       ZNF337-AS1           ZNF337-AS1                         -0.9198971
69       MIR219A2HG           MIR219A2HG                         -1.8896088
70        LINC01117            LINC01117                         -1.7541741
71         IPO9-AS1             IPO9-AS1                         -1.3286924
72        LINC02580            LINC02580                         -1.3816355
73         OTX2-AS1             OTX2-AS1                          2.9017871
74         LIX1-AS1             LIX1-AS1                         -1.2574453
75      SYNPO2L-AS1          SYNPO2L-AS1                         -1.2648196
76  ENSG00000303699          ANKRD17-AS1                         -1.5284179
77        LINC00240            LINC00240                         -1.5438983
78          BDNF-AS              BDNF-AS                         -0.7941867
79        LINC00862            LINC00862                          1.5586712
80        BCL10-AS1            BCL10-AS1                         -2.1383304
81        NR2F1-AS1            NR2F1-AS1                         -0.5012591
82        LINC02614            LINC02614                         -0.9224436
83         PDK4-AS1             PDK4-AS1                         -1.0305083
84       TMEM72-AS1           TMEM72-AS1                         -1.0091249
85       UBE2D3-AS1           UBE2D3-AS1                          1.6360227
86        EIF1B-AS1            EIF1B-AS1                         -0.5186210
87        DAAM2-AS1            DAAM2-AS1                         -1.7214142
88         MIR9-3HG             MIR9-3HG                         -1.0149620
89        LSAMP-AS1            LSAMP-AS1                         -1.4696069
90  ENSG00000225339           SMIM29-AS1                          1.5609970
91        LINC00472            LINC00472                          0.9223688
92        ITGA9-AS1            ITGA9-AS1                         -0.5956222
93        ZFPM2-AS1            ZFPM2-AS1                         -1.9082963
94        LINC00467            LINC00467                         -1.3848838
95        LINC00844            LINC00844                         -0.8087702
96        ZFHX3-AS1            ZFHX3-AS1                         -1.6656193
97  ENSG00000287158            LINC03214                         -1.4928563
98        LINC01994            LINC01994                         -0.8380970
99  ENSG00000258162           PPFIA2-AS2                         -1.5247043
100       MIR3659HG            MIR3659HG                          1.5856483
101     JAKMIP2-AS1          JAKMIP2-AS1                         -1.3164264
102        RHOQ-AS1             RHOQ-AS1                         -1.7468010
103       LINC02796            LINC02796                         -0.6065784
104       LINC02934            LINC02934                         -0.4288249
105       PRKCA-AS1            PRKCA-AS1                         -0.8366604
106       DPP10-AS3            DPP10-AS3                         -1.3361915
107       RBMS3-AS3            RBMS3-AS3                         -1.5543115
108           AP1AR                AP1AR                          1.4325981
109       LINC03051            LINC03051                          0.4705735
110       LINC02895            LINC02895                         -0.6752028
    p_val_adj_reactive_vs_homeostatic pct.1_reactive pct.2_homeostatic
1                       7.531054e-150          0.999             0.999
2                       3.217635e-142          0.982             0.973
3                        1.110663e-96          0.490             0.805
4                        2.329931e-71          0.778             0.929
5                        5.668776e-74          0.508             0.236
6                        3.898459e-29          0.506             0.307
7                        3.852364e-63          0.465             0.742
8                        3.239197e-43          0.162             0.015
9                        5.064069e-48          0.169             0.406
10                       5.037861e-37          0.061             0.229
11                       2.687424e-45          0.048             0.230
12                       2.245548e-29          0.836             0.818
13                       1.320335e-42          0.643             0.837
14                       2.420831e-26          0.010             0.106
15                       2.568512e-39          0.064             0.239
16                       8.304380e-52          0.319             0.567
17                       4.620217e-22          0.003             0.078
18                       2.254361e-26          0.019             0.125
19                       1.138365e-39          0.055             0.226
20                       1.491509e-31          0.063             0.219
21                       2.997658e-34          0.067             0.232
22                       6.510260e-20          0.013             0.095
23                       2.371079e-22          0.095             0.234
24                       5.578605e-21          0.525             0.708
25                       1.251068e-05          0.051             0.012
26                       6.826476e-27          0.076             0.225
27                       3.420788e-20          0.006             0.080
28                       1.476041e-32          0.162             0.369
29                       2.343689e-19          0.359             0.552
30                       3.494285e-21          0.055             0.175
31                       3.023175e-23          0.021             0.120
32                       4.971655e-29          0.711             0.625
33                       3.112172e-17          0.007             0.075
34                       3.222778e-19          0.052             0.163
35                       9.870437e-17          0.020             0.099
36                       2.104432e-19          0.016             0.100
37                       1.479314e-21          0.061             0.183
38                       3.463486e-15          0.254             0.408
39                       1.372355e-12          0.152             0.279
40                       1.277363e-19          0.060             0.178
41                       1.698291e-16          0.031             0.119
42                       9.932642e-18          0.104             0.234
43                       2.567255e-11          0.177             0.083
44                       8.193928e-18          0.023             0.109
45                       4.533165e-17          0.247             0.126
46                       8.319323e-10          0.072             0.016
47                       1.104988e-07          0.207             0.123
48                       1.490042e-10          0.150             0.263
49                       1.165603e-13          0.034             0.115
50                       8.703296e-12          0.026             0.094
51                       5.590474e-10          0.014             0.068
52                       4.050410e-15          0.048             0.144
53                       1.642947e-11          0.014             0.073
54                       2.308796e-04          0.187             0.254
55                       6.921594e-11          0.011             0.065
56                       4.400615e-11          0.017             0.078
57                       3.655561e-19          0.241             0.413
58                       3.007789e-14          0.073             0.181
59                       4.258019e-16          0.064             0.173
60                       2.123997e-11          0.012             0.068
61                       2.003744e-08          0.033             0.096
62                       4.434546e-15          0.169             0.312
63                       1.663182e-11          0.017             0.080
64                       1.042241e-05          0.054             0.013
65                       1.767182e-13          0.012             0.075
66                       2.808869e-11          0.015             0.074
67                       8.706967e-10          0.053             0.132
68                       1.408456e-11          0.059             0.150
69                       2.947967e-06          0.020             0.067
70                       3.181638e-07          0.019             0.068
71                       5.277608e-12          0.037             0.116
72                       6.212818e-12          0.045             0.127
73                       2.448193e-09          0.081             0.023
74                       1.435700e-11          0.065             0.156
75                       3.363365e-13          0.041             0.127
76                       5.706931e-07          0.041             0.103
77                       4.163614e-07          0.021             0.072
78                       3.282729e-10          0.121             0.228
79                       1.107380e-06          0.091             0.034
80                       4.561151e-09          0.019             0.074
81                       6.773300e-12          0.330             0.475
82                       4.979919e-12          0.129             0.242
83                       2.349247e-11          0.067             0.158
84                       1.666430e-11          0.080             0.178
85                       1.691957e-06          0.112             0.049
86                       2.362974e-09          0.236             0.362
87                       1.194161e-09          0.029             0.093
88                       1.303006e-09          0.081             0.171
89                       8.009277e-07          0.032             0.089
90                       1.352302e-08          0.179             0.096
91                       8.015808e-06          0.458             0.421
92                       5.918311e-11          0.154             0.275
93                       1.982926e-05          0.019             0.063
94                       1.892471e-07          0.031             0.089
95                       1.232605e-09          0.101             0.200
96                       1.276877e-07          0.028             0.085
97                       3.588883e-07          0.037             0.098
98                       1.670540e-05          0.072             0.142
99                       7.016993e-05          0.024             0.070
100                      5.929153e-04          0.087             0.039
101                      1.995836e-04          0.031             0.078
102                      3.953795e-04          0.024             0.066
103                      2.010877e-06          0.120             0.209
104                      3.256543e-07          0.264             0.388
105                      7.953078e-03          0.070             0.125
106                      4.968059e-05          0.025             0.071
107                      6.315568e-04          0.024             0.065
108                      2.143264e-02          0.074             0.034
109                      6.502419e-05          0.736             0.746
110                      6.031012e-03          0.073             0.130
                                                           GENENAME
1            metastasis associated lung adenocarcinoma transcript 1
2                         nuclear paraspeckle assembly transcript 1
3                                                  MIR9-1 host gene
4                                              OBI1 antisense RNA 1
5                                           SLC44A3 antisense RNA 1
6                                    X inactive specific transcript
7                                                  MIR9-2 host gene
8                                            PARD6G antisense RNA 1
9                                              POT1 antisense RNA 1
10                                            PCDH9 antisense RNA 2
11                                             UFL1 antisense RNA 1
12   long intergenic non-protein coding RNA, p53 induced transcript
13                                 small nucleolar RNA host gene 14
14                      long intergenic non-protein coding RNA 2232
15                            GNG12, DIRAS3 and WLS antisense RNA 1
16                                                MIR4300 host gene
17                                     HOXB cluster antisense RNA 1
18                                             PAX8 antisense RNA 1
19                                  ZBTB47 and NKTR antisense RNA 1
20                       long intergenic non-protein coding RNA 412
21                      long intergenic non-protein coding RNA 3122
22                                            A2ML1 antisense RNA 1
23                                             RFX4 antisense RNA 1
24                                            LMCD1 antisense RNA 1
25                      long intergenic non-protein coding RNA 2608
26                      long intergenic non-protein coding RNA 1376
27                      long intergenic non-protein coding RNA 1727
28                                          SLC38A4 antisense RNA 1
29                      long intergenic non-protein coding RNA 1748
30                                           HECTD2 antisense RNA 1
31                                             HEY2 antisense RNA 1
32                                    PTCHD1 and PHEX antisense RNA
33                                             LRP4 antisense RNA 1
34                      long intergenic non-protein coding RNA 1572
35                                             ANK2 antisense RNA 1
36                                             PKIA antisense RNA 1
37                                             DBX2 antisense RNA 1
38                                           ENTPD1 antisense RNA 1
39                                   GBX2 and ASB18 antisense RNA 1
40                       long intergenic non-protein coding RNA 173
41                                            RAP2C antisense RNA 1
42                                           RASSF8 antisense RNA 1
43                                             TET2 antisense RNA 1
44                                             LIFR antisense RNA 1
45                                            BAALC antisense RNA 1
46                                            SOCS2 antisense RNA 1
47                adaptor related protein complex 1 subunit sigma 2
48                                           GASK1B antisense RNA 1
49                       long intergenic non-protein coding RNA 960
50                                          ATP13A4 antisense RNA 1
51                      long intergenic non-protein coding RNA 1414
52                                          SLC28A2 antisense RNA 1
53                                                MIR4500 host gene
54                       long intergenic non-protein coding RNA 499
55                                           MIDEAS antisense RNA 1
56                                            SNED1 antisense RNA 1
57                                            MEF2C antisense RNA 1
58                                           HEXIM2 antisense RNA 1
59                              ZKSCAN7 ZNF cluster antisense RNA 1
60                      long intergenic non-protein coding RNA 3062
61                                  CALCRL and TFPI antisense RNA 1
62                                            FSIP2 antisense RNA 1
63                                             USP3 antisense RNA 1
64                       long intergenic non-protein coding RNA 378
65                                          NECTIN3 antisense RNA 1
66                                             WEE2 antisense RNA 1
67                                            PDE7B antisense RNA 1
68                                           ZNF337 antisense RNA 1
69                                               MIR219A2 host gene
70                      long intergenic non-protein coding RNA 1117
71                                             IPO9 antisense RNA 1
72                      long intergenic non-protein coding RNA 2580
73                                             OTX2 antisense RNA 1
74                                   LIX1 and RIOK2 antisense RNA 1
75                                          SYNPO2L antisense RNA 1
76                                           ANKRD17 antisense RNA1
77                       long intergenic non-protein coding RNA 240
78                                               BDNF antisense RNA
79                       long intergenic non-protein coding RNA 862
80                                            BCL10 antisense RNA 1
81                                 NR2F1 regulatory antisense RNA 1
82                      long intergenic non-protein coding RNA 2614
83                                             PDK4 antisense RNA 1
84                                           TMEM72 antisense RNA 1
85                                           UBE2D3 antisense RNA 1
86                                            EIF1B antisense RNA 1
87                                            DAAM2 antisense RNA 1
88                                                 MIR9-3 host gene
89                                            LSAMP antisense RNA 1
90                                           SMIM29 antisense RNA 1
91                       long intergenic non-protein coding RNA 472
92                                            ITGA9 antisense RNA 1
93                                            ZFPM2 antisense RNA 1
94                       long intergenic non-protein coding RNA 467
95                       long intergenic non-protein coding RNA 844
96                                            ZFHX3 antisense RNA 1
97                      long intergenic non-protein coding RNA 3214
98                      long intergenic non-protein coding RNA 1994
99                                           PPFIA2 antisense RNA 2
100                                               MIR3659 host gene
101                                         JAKMIP2 antisense RNA 1
102                                            RHOQ antisense RNA 1
103                     long intergenic non-protein coding RNA 2796
104                     long intergenic non-protein coding RNA 2934
105                                           PRKCA antisense RNA 1
106                                           DPP10 antisense RNA 3
107                                           RBMS3 antisense RNA 3
108 adaptor related protein complex 1 associated regulatory protein
109                     long intergenic non-protein coding RNA 3051
110                     long intergenic non-protein coding RNA 2895
    avg_log2FC_PD_vs_C p_val_adj_PD_vs_C pct.1_PD pct.2_C same_direction
1           -1.0785343     1.865112e-203    0.999   0.999           TRUE
2            0.8786913     3.328073e-112    0.978   0.969           TRUE
3           -0.6348170      7.969543e-50    0.559   0.729           TRUE
4           -0.6859095      4.279446e-73    0.753   0.874           TRUE
5            1.6386193      5.365303e-49    0.406   0.229           TRUE
6            1.2858607      1.699511e-82    0.563   0.321           TRUE
7           -0.5590838      3.337703e-32    0.541   0.682           TRUE
8            2.7031355      3.111727e-34    0.118   0.022           TRUE
9           -1.1404088      1.163515e-32    0.208   0.354           TRUE
10          -1.7008230      2.031888e-33    0.071   0.185           TRUE
11          -1.4241608      1.211450e-24    0.100   0.206           TRUE
12           0.5638433      3.761286e-42    0.856   0.811           TRUE
13          -0.5304722      1.524741e-28    0.684   0.788           TRUE
14          -3.3450042      5.692130e-36    0.009   0.084           TRUE
15          -1.2630328      9.127518e-23    0.087   0.185           TRUE
16          -0.3826847      3.402057e-06    0.402   0.481           TRUE
17          -4.0556306      9.086220e-28    0.005   0.062           TRUE
18          -2.0379081      3.852329e-26    0.023   0.096           TRUE
19          -1.1977744      1.730185e-13    0.121   0.203           TRUE
20          -1.0041436      1.908970e-14    0.108   0.192           TRUE
21          -0.7953887      2.527353e-11    0.132   0.213           TRUE
22          -2.2663428      2.598023e-20    0.015   0.071           TRUE
23          -1.4020254      2.488793e-19    0.095   0.188           TRUE
24          -0.4804939      1.602651e-22    0.553   0.682           TRUE
25           3.3371588      8.973627e-33    0.092   0.011           TRUE
26          -0.9334588      2.621275e-13    0.120   0.205           TRUE
27          -2.1462329      3.682758e-16    0.022   0.076           TRUE
28          -0.5356175      6.442011e-08    0.227   0.311           TRUE
29          -0.5107564      2.094936e-18    0.365   0.491           TRUE
30          -1.0857890      2.722708e-14    0.077   0.153           TRUE
31          -1.4310725      3.328734e-10    0.044   0.098           TRUE
32           0.3840640      3.855021e-07    0.652   0.606           TRUE
33          -2.4653985      2.536101e-13    0.014   0.057           TRUE
34          -1.2175268      7.039090e-14    0.066   0.137           TRUE
35          -2.0617487      7.873702e-13    0.027   0.077           TRUE
36          -1.7806304      5.116827e-10    0.032   0.080           TRUE
37          -1.0621147      9.223505e-10    0.082   0.147           TRUE
38          -0.6912777      3.844297e-16    0.270   0.382           TRUE
39          -0.8578170      1.973130e-18    0.140   0.247           TRUE
40          -0.8934571      7.264393e-11    0.069   0.135           TRUE
41          -1.2403898      7.949843e-12    0.053   0.114           TRUE
42          -0.8599095      4.999190e-10    0.125   0.200           TRUE
43           1.1735145      2.246857e-15    0.173   0.086           TRUE
44          -1.3251389      9.795100e-08    0.051   0.100           TRUE
45           1.2507027      1.965654e-08    0.190   0.119           TRUE
46           2.5328871      3.205104e-13    0.061   0.014           TRUE
47           1.2481882      7.443896e-18    0.215   0.116           TRUE
48          -0.9390244      7.411156e-16    0.138   0.233           TRUE
49          -1.4989419      6.298500e-10    0.038   0.087           TRUE
50          -1.8837620      6.789299e-11    0.026   0.072           TRUE
51          -2.2000756      1.084779e-11    0.019   0.062           TRUE
52          -1.0324631      2.030816e-08    0.072   0.131           TRUE
53          -1.8622106      1.004560e-09    0.020   0.060           TRUE
54          -1.4627475      1.924047e-18    0.145   0.241           TRUE
55          -1.7928889      3.561712e-10    0.014   0.051           TRUE
56          -1.6182813      8.616760e-10    0.022   0.064           TRUE
57          -0.3033979      1.693342e-03    0.323   0.398           TRUE
58          -0.6881924      1.129753e-07    0.100   0.164           TRUE
59          -0.7325966      1.846123e-05    0.094   0.149           TRUE
60          -1.7315357      2.687633e-07    0.019   0.054           TRUE
61          -1.6336982      2.237494e-11    0.033   0.083           TRUE
62          -0.5366656      4.912220e-06    0.207   0.278           TRUE
63          -1.4075043      1.038754e-07    0.026   0.066           TRUE
64           1.9176396      1.354137e-12    0.061   0.015           TRUE
65          -1.5334647      2.083619e-04    0.028   0.061           TRUE
66          -1.5212145      3.770219e-07    0.023   0.060           TRUE
67          -1.2077131      1.396314e-09    0.048   0.101           TRUE
68          -0.8570729      8.650509e-08    0.076   0.134           TRUE
69          -1.9527912      1.067118e-10    0.024   0.068           TRUE
70          -1.6799383      5.811928e-10    0.015   0.053           TRUE
71          -1.0080648      6.225659e-05    0.050   0.092           TRUE
72          -0.9498066      7.167198e-05    0.066   0.111           TRUE
73           1.4726849      2.411075e-05    0.066   0.029           TRUE
74          -0.8830735      3.146696e-05    0.087   0.139           TRUE
75          -0.8009231      1.895176e-03    0.064   0.106           TRUE
76          -1.5731402      1.310611e-08    0.032   0.076           TRUE
77          -1.6760204      3.061914e-08    0.026   0.066           TRUE
78          -0.6863693      9.725967e-07    0.139   0.206           TRUE
79           1.0898264      6.905976e-09    0.096   0.043           TRUE
80          -1.5546684      4.077856e-05    0.027   0.061           TRUE
81          -0.3255635      8.698939e-05    0.385   0.458           TRUE
82          -0.6547661      9.459607e-04    0.168   0.223           TRUE
83          -0.7743301      2.033560e-03    0.090   0.135           TRUE
84          -0.5999107      2.813741e-03    0.114   0.164           TRUE
85           1.1927386      9.762336e-07    0.100   0.051           TRUE
86          -0.4332346      8.009286e-05    0.293   0.360           TRUE
87          -1.2034929      1.563902e-02    0.039   0.069           TRUE
88          -0.7669306      1.351762e-03    0.100   0.148           TRUE
89          -1.3777549      3.701280e-05    0.040   0.078           TRUE
90           1.1038821      1.475434e-03    0.128   0.082           TRUE
91           0.5760819      3.018961e-07    0.482   0.420           TRUE
92          -0.3769998      1.344479e-02    0.211   0.268           TRUE
93          -1.5876122      5.350543e-05    0.020   0.051           TRUE
94          -1.0521023      1.956912e-03    0.043   0.079           TRUE
95          -0.5279199      4.012277e-02    0.120   0.166           TRUE
96          -1.1075559      1.683174e-02    0.042   0.074           TRUE
97          -1.1679230      8.163301e-03    0.047   0.081           TRUE
98          -0.8802699      2.367852e-05    0.072   0.121           TRUE
99          -1.3962449      2.191334e-04    0.027   0.060           TRUE
100          1.1126372      1.843104e-05    0.090   0.046           TRUE
101         -1.3442059      3.803868e-04    0.029   0.061           TRUE
102         -1.6176164      1.415566e-03    0.026   0.055           TRUE
103         -0.5799762      4.504183e-03    0.128   0.179           TRUE
104         -0.3467941      1.448512e-02    0.300   0.366           TRUE
105         -1.0205611      8.579029e-06    0.054   0.100           TRUE
106         -1.1193793      9.337767e-03    0.026   0.054           TRUE
107         -1.3326728      2.169708e-03    0.024   0.052           TRUE
108          1.0889663      8.213554e-04    0.070   0.034           TRUE
109          0.2826169      5.626406e-03    0.730   0.721           TRUE
110         -0.8321417      9.758364e-04    0.074   0.118           TRUE
    priority_score cluster_support max_cluster_log2FC min_cluster_p_val_adj
1       354.015516         2;4;5;8          1.3149729          2.926163e-97
2       255.223524         1;6;7;8          1.4606620         1.946829e-151
3       146.842468         2;4;5;7          0.7948607          6.914674e-40
4       144.467581         2;4;6;7          0.9249589          7.845489e-84
5       125.350396               0          2.6318030         4.176317e-204
6       112.503255      0;3;4;7;10          1.1923412         3.021222e-125
7        95.417476             2;4          0.6745209          9.437479e-26
8        82.441924             6;8          4.1735190         3.363576e-214
9        81.949433             2;4          1.1451353          2.298637e-31
10       72.660344           2;4;5          1.3935093          1.109563e-12
11       72.189536               2          1.3424072          1.360686e-14
12       71.318503           3;6;8          0.7965285          4.272232e-41
13       70.969735               2          0.8193956          1.111942e-41
14       67.754023            5;11          3.6210213         6.509256e-107
15       64.006673           2;4;5          1.4041813          4.308952e-23
16       58.307826           2;3;5          1.8450863         9.231737e-122
17       56.938886             2;5          2.9027138          2.636680e-36
18       55.550349             2;5          2.4566705          3.170504e-46
19       55.221473             3;5          1.4767218          1.459588e-24
20       47.203896             4;5          0.8428831          7.421299e-05
21       46.799253             4;7          0.9274611          1.787341e-16
22       43.885270             2;4          1.6467829          4.940196e-19
23       43.199705           2;4;5          1.5930094          1.596581e-15
24       43.052703             5;7          0.4457738          4.973616e-09
25       42.720101           1;6;7          1.6710392          1.689881e-20
26       41.258237               4          0.4509406          3.927515e-03
27       41.199102         2;10;11          4.6998013          2.416280e-30
28       40.584637           2;3;5          0.7505358          1.132269e-13
29       37.348681             2;5          0.6427965          6.295001e-11
30       36.496381             2;4          1.1059567          3.210999e-10
31       36.062049             2;5          1.3852956          1.791840e-09
32       35.926515           0;6;7          0.8676164          8.143973e-27
33       34.782422             2;4          2.3657208          3.717968e-16
34       34.322020             4;5          1.1045737          7.269607e-08
35       32.775540               5          2.5314869          1.754555e-23
36       32.658673               5          2.4170409          2.764130e-24
37       32.655858             2;5          1.2350251          4.092195e-12
38       31.245598            <NA>                 NA                    NA
39       31.216196           2;5;7          1.1462196          7.985402e-19
40       31.176916             2;5          1.2749371          7.326753e-11
41       29.850350            <NA>                 NA                    NA
42       28.229413               2          1.0222454          1.488441e-06
43       27.958578             6;7          2.2797812          1.333389e-59
44       27.785250               5          1.2771772          1.360718e-03
45       27.270696               0          2.7566790          1.200305e-78
46       27.010758               0          2.8286122          8.106778e-27
47       26.728447             0;3          1.5687449          1.019470e-24
48       26.658016               4          0.8293094          1.575930e-15
49       25.441690               5          2.1796840          5.237064e-23
50       25.172387               4          1.8819046          5.391534e-23
51       24.839213            2;10          2.8311254          2.494682e-34
52       24.371913             2;7          1.0704871          9.315530e-03
53       24.101035             2;5          2.1459210          1.322867e-14
54       24.082050          4;8;10          3.4282197          0.000000e+00
55       23.505812             2;4          1.6265430          2.576288e-05
56       23.082742               5          2.0470659          3.612157e-14
57       22.245884             3;7          0.9091691          6.246858e-26
58       22.094919               7          0.4143896          8.413223e-03
59       21.938076               4          0.8738634          7.876410e-14
60       21.560609             2;4          1.8210760          5.930170e-22
61       21.442051             2;5          1.4127708          2.597650e-07
62       20.958046               2          0.6580104          6.408539e-05
63       20.946831             2;4          1.7040296          1.778819e-04
64       20.894712             0;3          1.8897189          8.321567e-17
65       20.874848               2          1.5981382          4.199725e-02
66       20.799186               5          1.4883684          1.762868e-05
67       20.242445             2;4          1.6355935          7.396749e-14
68       19.691185               4          0.8476863          5.142744e-14
69       19.344665             5;9          1.7112196          4.223296e-08
70       19.167141               5          2.6165048          6.948591e-35
71       17.820135               4          1.2404632          1.797973e-15
72       17.682804            <NA>                 NA                    NA
73       17.603416             7;8          3.4438702          3.668336e-63
74       17.485600               2          0.9192580          2.025225e-02
75       17.261319               4          0.5470568          1.309821e-03
76       17.227682             4;5          2.0368111          5.405044e-10
77       17.114455               5          1.6956866          4.117233e-10
78       16.976388               2          0.8261983          3.513250e-05
79       16.764976           3;6;8          1.3677539          2.616717e-08
80       16.423492               2          1.2887431          3.758900e-03
81       16.056556             3;4          0.5010869          1.400262e-09
82       15.904114            <NA>                 NA                    NA
83       15.125653               4          0.2756608          3.954770e-02
84       14.937964               4          0.7539576          2.823794e-12
85       14.610818             6;8          1.5674839          3.087805e-12
86       13.674803               7          0.7806955          1.070834e-14
87       13.653635             4;5          1.6322204          4.532332e-05
88       13.536046               2          1.5494248          1.092159e-25
89       13.375417            <NA>                 NA                    NA
90       13.364886               0          2.7640326          6.933817e-78
91       13.114646           6;7;8          1.5762592          2.152036e-71
92       13.071870             3;7          0.7464233          5.393400e-12
93       12.470204               5          1.5966198          9.232406e-03
94       11.868386            <NA>                 NA                    NA
95       11.642475               5          1.4773086          4.441577e-25
96       11.440897               4          1.1097092          1.199136e-04
97       11.193954             2;7          1.2583703          2.484989e-04
98       11.121155               2          1.4438382          3.915877e-15
99       10.734090             2;9          1.8534743          4.156685e-04
100      10.659743               7          1.5354408          2.199742e-28
101       9.780282            <NA>                 NA                    NA
102       9.616473               5          1.8828749          5.360613e-06
103       9.229553               2          0.9005814          1.062043e-05
104       9.101940             7;8          0.8216365          8.853810e-06
105       9.023248               4          1.2247618          4.484259e-13
106       8.789141               5          2.6642721          5.164084e-30
107       8.750171               2          1.7099427          3.936510e-04
108       7.275958            <NA>                 NA                    NA
109       7.189884               6          0.3686788          1.478167e-06
110       6.737577               4          0.5336785          2.611942e-02
driver_lncRNAs <- priority_astro_lncRNAs %>%
  filter(
    same_direction,
    avg_log2FC_reactive_vs_homeostatic > 0,
    avg_log2FC_PD_vs_C > 0
  )

defender_lncRNAs <- priority_astro_lncRNAs %>%
  filter(
    same_direction,
    avg_log2FC_reactive_vs_homeostatic < 0,
    avg_log2FC_PD_vs_C < 0
  )

driver_lncRNAs
              gene gene_symbol_for_plot avg_log2FC_reactive_vs_homeostatic
1            NEAT1                NEAT1                          1.3745627
2      SLC44A3-AS1          SLC44A3-AS1                          2.1948605
3             XIST                 XIST                          1.0386112
4       PARD6G-AS1           PARD6G-AS1                          3.7422278
5        LINC-PINT            LINC-PINT                          0.6813181
6        LINC02608            LINC02608                          2.4331917
7        PTCHD1-AS            PTCHD1-AS                          0.8249788
8         TET2-AS1             TET2-AS1                          1.5461079
9        BAALC-AS1            BAALC-AS1                          1.9699019
10       SOCS2-AS1            SOCS2-AS1                          2.9038008
11           AP1S2                AP1S2                          1.3954165
12       LINC00378            LINC00378                          2.1267031
13        OTX2-AS1             OTX2-AS1                          2.9017871
14       LINC00862            LINC00862                          1.5586712
15      UBE2D3-AS1           UBE2D3-AS1                          1.6360227
16 ENSG00000225339           SMIM29-AS1                          1.5609970
17       LINC00472            LINC00472                          0.9223688
18       MIR3659HG            MIR3659HG                          1.5856483
19           AP1AR                AP1AR                          1.4325981
20       LINC03051            LINC03051                          0.4705735
   p_val_adj_reactive_vs_homeostatic pct.1_reactive pct.2_homeostatic
1                      3.217635e-142          0.982             0.973
2                       5.668776e-74          0.508             0.236
3                       3.898459e-29          0.506             0.307
4                       3.239197e-43          0.162             0.015
5                       2.245548e-29          0.836             0.818
6                       1.251068e-05          0.051             0.012
7                       4.971655e-29          0.711             0.625
8                       2.567255e-11          0.177             0.083
9                       4.533165e-17          0.247             0.126
10                      8.319323e-10          0.072             0.016
11                      1.104988e-07          0.207             0.123
12                      1.042241e-05          0.054             0.013
13                      2.448193e-09          0.081             0.023
14                      1.107380e-06          0.091             0.034
15                      1.691957e-06          0.112             0.049
16                      1.352302e-08          0.179             0.096
17                      8.015808e-06          0.458             0.421
18                      5.929153e-04          0.087             0.039
19                      2.143264e-02          0.074             0.034
20                      6.502419e-05          0.736             0.746
                                                          GENENAME
1                        nuclear paraspeckle assembly transcript 1
2                                          SLC44A3 antisense RNA 1
3                                   X inactive specific transcript
4                                           PARD6G antisense RNA 1
5   long intergenic non-protein coding RNA, p53 induced transcript
6                      long intergenic non-protein coding RNA 2608
7                                    PTCHD1 and PHEX antisense RNA
8                                             TET2 antisense RNA 1
9                                            BAALC antisense RNA 1
10                                           SOCS2 antisense RNA 1
11               adaptor related protein complex 1 subunit sigma 2
12                      long intergenic non-protein coding RNA 378
13                                            OTX2 antisense RNA 1
14                      long intergenic non-protein coding RNA 862
15                                          UBE2D3 antisense RNA 1
16                                          SMIM29 antisense RNA 1
17                      long intergenic non-protein coding RNA 472
18                                               MIR3659 host gene
19 adaptor related protein complex 1 associated regulatory protein
20                     long intergenic non-protein coding RNA 3051
   avg_log2FC_PD_vs_C p_val_adj_PD_vs_C pct.1_PD pct.2_C same_direction
1           0.8786913     3.328073e-112    0.978   0.969           TRUE
2           1.6386193      5.365303e-49    0.406   0.229           TRUE
3           1.2858607      1.699511e-82    0.563   0.321           TRUE
4           2.7031355      3.111727e-34    0.118   0.022           TRUE
5           0.5638433      3.761286e-42    0.856   0.811           TRUE
6           3.3371588      8.973627e-33    0.092   0.011           TRUE
7           0.3840640      3.855021e-07    0.652   0.606           TRUE
8           1.1735145      2.246857e-15    0.173   0.086           TRUE
9           1.2507027      1.965654e-08    0.190   0.119           TRUE
10          2.5328871      3.205104e-13    0.061   0.014           TRUE
11          1.2481882      7.443896e-18    0.215   0.116           TRUE
12          1.9176396      1.354137e-12    0.061   0.015           TRUE
13          1.4726849      2.411075e-05    0.066   0.029           TRUE
14          1.0898264      6.905976e-09    0.096   0.043           TRUE
15          1.1927386      9.762336e-07    0.100   0.051           TRUE
16          1.1038821      1.475434e-03    0.128   0.082           TRUE
17          0.5760819      3.018961e-07    0.482   0.420           TRUE
18          1.1126372      1.843104e-05    0.090   0.046           TRUE
19          1.0889663      8.213554e-04    0.070   0.034           TRUE
20          0.2826169      5.626406e-03    0.730   0.721           TRUE
   priority_score cluster_support max_cluster_log2FC min_cluster_p_val_adj
1      255.223524         1;6;7;8          1.4606620         1.946829e-151
2      125.350396               0          2.6318030         4.176317e-204
3      112.503255      0;3;4;7;10          1.1923412         3.021222e-125
4       82.441924             6;8          4.1735190         3.363576e-214
5       71.318503           3;6;8          0.7965285          4.272232e-41
6       42.720101           1;6;7          1.6710392          1.689881e-20
7       35.926515           0;6;7          0.8676164          8.143973e-27
8       27.958578             6;7          2.2797812          1.333389e-59
9       27.270696               0          2.7566790          1.200305e-78
10      27.010758               0          2.8286122          8.106778e-27
11      26.728447             0;3          1.5687449          1.019470e-24
12      20.894712             0;3          1.8897189          8.321567e-17
13      17.603416             7;8          3.4438702          3.668336e-63
14      16.764976           3;6;8          1.3677539          2.616717e-08
15      14.610818             6;8          1.5674839          3.087805e-12
16      13.364886               0          2.7640326          6.933817e-78
17      13.114646           6;7;8          1.5762592          2.152036e-71
18      10.659743               7          1.5354408          2.199742e-28
19       7.275958            <NA>                 NA                    NA
20       7.189884               6          0.3686788          1.478167e-06
defender_lncRNAs
              gene gene_symbol_for_plot avg_log2FC_reactive_vs_homeostatic
1           MALAT1               MALAT1                         -1.0845420
2         MIR9-1HG             MIR9-1HG                         -1.1546672
3         OBI1-AS1             OBI1-AS1                         -0.7804023
4         MIR9-2HG             MIR9-2HG                         -0.9675675
5         POT1-AS1             POT1-AS1                         -1.5792964
6        PCDH9-AS2            PCDH9-AS2                         -1.9696666
7         UFL1-AS1             UFL1-AS1                         -2.2780168
8           SNHG14               SNHG14                         -0.7431429
9        LINC02232            LINC02232                         -3.5482579
10       GNG12-AS1            GNG12-AS1                         -2.1136746
11       MIR4300HG            MIR4300HG                         -1.3761905
12        HOXB-AS1             HOXB-AS1                         -4.5063008
13        PAX8-AS1             PAX8-AS1                         -2.4511875
14      ZBTB47-AS1           ZBTB47-AS1                         -2.3180731
15       LINC00412            LINC00412                         -1.6541773
16       LINC03122            LINC03122                         -1.8833119
17       A2ML1-AS1            A2ML1-AS1                         -2.8471687
18 ENSG00000257545             RFX4-AS1                         -1.5686148
19       LMCD1-AS1            LMCD1-AS1                         -0.5235736
20       LINC01376            LINC01376                         -1.5774871
21       LINC01727            LINC01727                         -4.1531683
22     SLC38A4-AS1          SLC38A4-AS1                         -1.0271390
23       LINC01748            LINC01748                         -0.5289954
24      HECTD2-AS1           HECTD2-AS1                         -1.3889513
25        HEY2-AS1             HEY2-AS1                         -2.6337186
26        LRP4-AS1             LRP4-AS1                         -3.2142539
27       LINC01572            LINC01572                         -1.4602397
28        ANK2-AS1             ANK2-AS1                         -2.6043069
29        PKIA-AS1             PKIA-AS1                         -2.9101779
30        DBX2-AS1             DBX2-AS1                         -1.7286998
31      ENTPD1-AS1           ENTPD1-AS1                         -0.6786507
32        GBX2-AS1             GBX2-AS1                         -0.7910011
33       LINC00173            LINC00173                         -1.2509725
34       RAP2C-AS1            RAP2C-AS1                         -1.7403309
35      RASSF8-AS1           RASSF8-AS1                         -1.0654679
36        LIFR-AS1             LIFR-AS1                         -2.3646125
37      GASK1B-AS1           GASK1B-AS1                         -0.7620764
38       LINC00960            LINC00960                         -1.8085364
39     ATP13A4-AS1          ATP13A4-AS1                         -2.0601332
40       LINC01414            LINC01414                         -2.4219273
41     SLC28A2-AS1          SLC28A2-AS1                         -1.2546195
42       MIR4500HG            MIR4500HG                         -2.4564245
43       LINC00499            LINC00499                         -1.2669032
44      MIDEAS-AS1           MIDEAS-AS1                         -2.1047880
45       SNED1-AS1            SNED1-AS1                         -2.0433184
46       MEF2C-AS1            MEF2C-AS1                         -0.7341850
47      HEXIM2-AS1           HEXIM2-AS1                         -0.9379578
48     ZKSCAN7-AS1          ZKSCAN7-AS1                         -1.1009480
49       LINC03062            LINC03062                         -2.5855973
50      CALCRL-AS1           CALCRL-AS1                         -1.4599570
51       FSIP2-AS1            FSIP2-AS1                         -0.7595069
52        USP3-AS1             USP3-AS1                         -1.7767793
53     NECTIN3-AS1          NECTIN3-AS1                         -2.9074828
54        WEE2-AS1             WEE2-AS1                         -2.3028693
55       PDE7B-AS1            PDE7B-AS1                         -1.1195818
56      ZNF337-AS1           ZNF337-AS1                         -0.9198971
57      MIR219A2HG           MIR219A2HG                         -1.8896088
58       LINC01117            LINC01117                         -1.7541741
59        IPO9-AS1             IPO9-AS1                         -1.3286924
60       LINC02580            LINC02580                         -1.3816355
61        LIX1-AS1             LIX1-AS1                         -1.2574453
62     SYNPO2L-AS1          SYNPO2L-AS1                         -1.2648196
63 ENSG00000303699          ANKRD17-AS1                         -1.5284179
64       LINC00240            LINC00240                         -1.5438983
65         BDNF-AS              BDNF-AS                         -0.7941867
66       BCL10-AS1            BCL10-AS1                         -2.1383304
67       NR2F1-AS1            NR2F1-AS1                         -0.5012591
68       LINC02614            LINC02614                         -0.9224436
69        PDK4-AS1             PDK4-AS1                         -1.0305083
70      TMEM72-AS1           TMEM72-AS1                         -1.0091249
71       EIF1B-AS1            EIF1B-AS1                         -0.5186210
72       DAAM2-AS1            DAAM2-AS1                         -1.7214142
73        MIR9-3HG             MIR9-3HG                         -1.0149620
74       LSAMP-AS1            LSAMP-AS1                         -1.4696069
75       ITGA9-AS1            ITGA9-AS1                         -0.5956222
76       ZFPM2-AS1            ZFPM2-AS1                         -1.9082963
77       LINC00467            LINC00467                         -1.3848838
78       LINC00844            LINC00844                         -0.8087702
79       ZFHX3-AS1            ZFHX3-AS1                         -1.6656193
80 ENSG00000287158            LINC03214                         -1.4928563
81       LINC01994            LINC01994                         -0.8380970
82 ENSG00000258162           PPFIA2-AS2                         -1.5247043
83     JAKMIP2-AS1          JAKMIP2-AS1                         -1.3164264
84        RHOQ-AS1             RHOQ-AS1                         -1.7468010
85       LINC02796            LINC02796                         -0.6065784
86       LINC02934            LINC02934                         -0.4288249
87       PRKCA-AS1            PRKCA-AS1                         -0.8366604
88       DPP10-AS3            DPP10-AS3                         -1.3361915
89       RBMS3-AS3            RBMS3-AS3                         -1.5543115
90       LINC02895            LINC02895                         -0.6752028
   p_val_adj_reactive_vs_homeostatic pct.1_reactive pct.2_homeostatic
1                      7.531054e-150          0.999             0.999
2                       1.110663e-96          0.490             0.805
3                       2.329931e-71          0.778             0.929
4                       3.852364e-63          0.465             0.742
5                       5.064069e-48          0.169             0.406
6                       5.037861e-37          0.061             0.229
7                       2.687424e-45          0.048             0.230
8                       1.320335e-42          0.643             0.837
9                       2.420831e-26          0.010             0.106
10                      2.568512e-39          0.064             0.239
11                      8.304380e-52          0.319             0.567
12                      4.620217e-22          0.003             0.078
13                      2.254361e-26          0.019             0.125
14                      1.138365e-39          0.055             0.226
15                      1.491509e-31          0.063             0.219
16                      2.997658e-34          0.067             0.232
17                      6.510260e-20          0.013             0.095
18                      2.371079e-22          0.095             0.234
19                      5.578605e-21          0.525             0.708
20                      6.826476e-27          0.076             0.225
21                      3.420788e-20          0.006             0.080
22                      1.476041e-32          0.162             0.369
23                      2.343689e-19          0.359             0.552
24                      3.494285e-21          0.055             0.175
25                      3.023175e-23          0.021             0.120
26                      3.112172e-17          0.007             0.075
27                      3.222778e-19          0.052             0.163
28                      9.870437e-17          0.020             0.099
29                      2.104432e-19          0.016             0.100
30                      1.479314e-21          0.061             0.183
31                      3.463486e-15          0.254             0.408
32                      1.372355e-12          0.152             0.279
33                      1.277363e-19          0.060             0.178
34                      1.698291e-16          0.031             0.119
35                      9.932642e-18          0.104             0.234
36                      8.193928e-18          0.023             0.109
37                      1.490042e-10          0.150             0.263
38                      1.165603e-13          0.034             0.115
39                      8.703296e-12          0.026             0.094
40                      5.590474e-10          0.014             0.068
41                      4.050410e-15          0.048             0.144
42                      1.642947e-11          0.014             0.073
43                      2.308796e-04          0.187             0.254
44                      6.921594e-11          0.011             0.065
45                      4.400615e-11          0.017             0.078
46                      3.655561e-19          0.241             0.413
47                      3.007789e-14          0.073             0.181
48                      4.258019e-16          0.064             0.173
49                      2.123997e-11          0.012             0.068
50                      2.003744e-08          0.033             0.096
51                      4.434546e-15          0.169             0.312
52                      1.663182e-11          0.017             0.080
53                      1.767182e-13          0.012             0.075
54                      2.808869e-11          0.015             0.074
55                      8.706967e-10          0.053             0.132
56                      1.408456e-11          0.059             0.150
57                      2.947967e-06          0.020             0.067
58                      3.181638e-07          0.019             0.068
59                      5.277608e-12          0.037             0.116
60                      6.212818e-12          0.045             0.127
61                      1.435700e-11          0.065             0.156
62                      3.363365e-13          0.041             0.127
63                      5.706931e-07          0.041             0.103
64                      4.163614e-07          0.021             0.072
65                      3.282729e-10          0.121             0.228
66                      4.561151e-09          0.019             0.074
67                      6.773300e-12          0.330             0.475
68                      4.979919e-12          0.129             0.242
69                      2.349247e-11          0.067             0.158
70                      1.666430e-11          0.080             0.178
71                      2.362974e-09          0.236             0.362
72                      1.194161e-09          0.029             0.093
73                      1.303006e-09          0.081             0.171
74                      8.009277e-07          0.032             0.089
75                      5.918311e-11          0.154             0.275
76                      1.982926e-05          0.019             0.063
77                      1.892471e-07          0.031             0.089
78                      1.232605e-09          0.101             0.200
79                      1.276877e-07          0.028             0.085
80                      3.588883e-07          0.037             0.098
81                      1.670540e-05          0.072             0.142
82                      7.016993e-05          0.024             0.070
83                      1.995836e-04          0.031             0.078
84                      3.953795e-04          0.024             0.066
85                      2.010877e-06          0.120             0.209
86                      3.256543e-07          0.264             0.388
87                      7.953078e-03          0.070             0.125
88                      4.968059e-05          0.025             0.071
89                      6.315568e-04          0.024             0.065
90                      6.031012e-03          0.073             0.130
                                                 GENENAME avg_log2FC_PD_vs_C
1  metastasis associated lung adenocarcinoma transcript 1         -1.0785343
2                                        MIR9-1 host gene         -0.6348170
3                                    OBI1 antisense RNA 1         -0.6859095
4                                        MIR9-2 host gene         -0.5590838
5                                    POT1 antisense RNA 1         -1.1404088
6                                   PCDH9 antisense RNA 2         -1.7008230
7                                    UFL1 antisense RNA 1         -1.4241608
8                        small nucleolar RNA host gene 14         -0.5304722
9             long intergenic non-protein coding RNA 2232         -3.3450042
10                  GNG12, DIRAS3 and WLS antisense RNA 1         -1.2630328
11                                      MIR4300 host gene         -0.3826847
12                           HOXB cluster antisense RNA 1         -4.0556306
13                                   PAX8 antisense RNA 1         -2.0379081
14                        ZBTB47 and NKTR antisense RNA 1         -1.1977744
15             long intergenic non-protein coding RNA 412         -1.0041436
16            long intergenic non-protein coding RNA 3122         -0.7953887
17                                  A2ML1 antisense RNA 1         -2.2663428
18                                   RFX4 antisense RNA 1         -1.4020254
19                                  LMCD1 antisense RNA 1         -0.4804939
20            long intergenic non-protein coding RNA 1376         -0.9334588
21            long intergenic non-protein coding RNA 1727         -2.1462329
22                                SLC38A4 antisense RNA 1         -0.5356175
23            long intergenic non-protein coding RNA 1748         -0.5107564
24                                 HECTD2 antisense RNA 1         -1.0857890
25                                   HEY2 antisense RNA 1         -1.4310725
26                                   LRP4 antisense RNA 1         -2.4653985
27            long intergenic non-protein coding RNA 1572         -1.2175268
28                                   ANK2 antisense RNA 1         -2.0617487
29                                   PKIA antisense RNA 1         -1.7806304
30                                   DBX2 antisense RNA 1         -1.0621147
31                                 ENTPD1 antisense RNA 1         -0.6912777
32                         GBX2 and ASB18 antisense RNA 1         -0.8578170
33             long intergenic non-protein coding RNA 173         -0.8934571
34                                  RAP2C antisense RNA 1         -1.2403898
35                                 RASSF8 antisense RNA 1         -0.8599095
36                                   LIFR antisense RNA 1         -1.3251389
37                                 GASK1B antisense RNA 1         -0.9390244
38             long intergenic non-protein coding RNA 960         -1.4989419
39                                ATP13A4 antisense RNA 1         -1.8837620
40            long intergenic non-protein coding RNA 1414         -2.2000756
41                                SLC28A2 antisense RNA 1         -1.0324631
42                                      MIR4500 host gene         -1.8622106
43             long intergenic non-protein coding RNA 499         -1.4627475
44                                 MIDEAS antisense RNA 1         -1.7928889
45                                  SNED1 antisense RNA 1         -1.6182813
46                                  MEF2C antisense RNA 1         -0.3033979
47                                 HEXIM2 antisense RNA 1         -0.6881924
48                    ZKSCAN7 ZNF cluster antisense RNA 1         -0.7325966
49            long intergenic non-protein coding RNA 3062         -1.7315357
50                        CALCRL and TFPI antisense RNA 1         -1.6336982
51                                  FSIP2 antisense RNA 1         -0.5366656
52                                   USP3 antisense RNA 1         -1.4075043
53                                NECTIN3 antisense RNA 1         -1.5334647
54                                   WEE2 antisense RNA 1         -1.5212145
55                                  PDE7B antisense RNA 1         -1.2077131
56                                 ZNF337 antisense RNA 1         -0.8570729
57                                     MIR219A2 host gene         -1.9527912
58            long intergenic non-protein coding RNA 1117         -1.6799383
59                                   IPO9 antisense RNA 1         -1.0080648
60            long intergenic non-protein coding RNA 2580         -0.9498066
61                         LIX1 and RIOK2 antisense RNA 1         -0.8830735
62                                SYNPO2L antisense RNA 1         -0.8009231
63                                 ANKRD17 antisense RNA1         -1.5731402
64             long intergenic non-protein coding RNA 240         -1.6760204
65                                     BDNF antisense RNA         -0.6863693
66                                  BCL10 antisense RNA 1         -1.5546684
67                       NR2F1 regulatory antisense RNA 1         -0.3255635
68            long intergenic non-protein coding RNA 2614         -0.6547661
69                                   PDK4 antisense RNA 1         -0.7743301
70                                 TMEM72 antisense RNA 1         -0.5999107
71                                  EIF1B antisense RNA 1         -0.4332346
72                                  DAAM2 antisense RNA 1         -1.2034929
73                                       MIR9-3 host gene         -0.7669306
74                                  LSAMP antisense RNA 1         -1.3777549
75                                  ITGA9 antisense RNA 1         -0.3769998
76                                  ZFPM2 antisense RNA 1         -1.5876122
77             long intergenic non-protein coding RNA 467         -1.0521023
78             long intergenic non-protein coding RNA 844         -0.5279199
79                                  ZFHX3 antisense RNA 1         -1.1075559
80            long intergenic non-protein coding RNA 3214         -1.1679230
81            long intergenic non-protein coding RNA 1994         -0.8802699
82                                 PPFIA2 antisense RNA 2         -1.3962449
83                                JAKMIP2 antisense RNA 1         -1.3442059
84                                   RHOQ antisense RNA 1         -1.6176164
85            long intergenic non-protein coding RNA 2796         -0.5799762
86            long intergenic non-protein coding RNA 2934         -0.3467941
87                                  PRKCA antisense RNA 1         -1.0205611
88                                  DPP10 antisense RNA 3         -1.1193793
89                                  RBMS3 antisense RNA 3         -1.3326728
90            long intergenic non-protein coding RNA 2895         -0.8321417
   p_val_adj_PD_vs_C pct.1_PD pct.2_C same_direction priority_score
1      1.865112e-203    0.999   0.999           TRUE     354.015516
2       7.969543e-50    0.559   0.729           TRUE     146.842468
3       4.279446e-73    0.753   0.874           TRUE     144.467581
4       3.337703e-32    0.541   0.682           TRUE      95.417476
5       1.163515e-32    0.208   0.354           TRUE      81.949433
6       2.031888e-33    0.071   0.185           TRUE      72.660344
7       1.211450e-24    0.100   0.206           TRUE      72.189536
8       1.524741e-28    0.684   0.788           TRUE      70.969735
9       5.692130e-36    0.009   0.084           TRUE      67.754023
10      9.127518e-23    0.087   0.185           TRUE      64.006673
11      3.402057e-06    0.402   0.481           TRUE      58.307826
12      9.086220e-28    0.005   0.062           TRUE      56.938886
13      3.852329e-26    0.023   0.096           TRUE      55.550349
14      1.730185e-13    0.121   0.203           TRUE      55.221473
15      1.908970e-14    0.108   0.192           TRUE      47.203896
16      2.527353e-11    0.132   0.213           TRUE      46.799253
17      2.598023e-20    0.015   0.071           TRUE      43.885270
18      2.488793e-19    0.095   0.188           TRUE      43.199705
19      1.602651e-22    0.553   0.682           TRUE      43.052703
20      2.621275e-13    0.120   0.205           TRUE      41.258237
21      3.682758e-16    0.022   0.076           TRUE      41.199102
22      6.442011e-08    0.227   0.311           TRUE      40.584637
23      2.094936e-18    0.365   0.491           TRUE      37.348681
24      2.722708e-14    0.077   0.153           TRUE      36.496381
25      3.328734e-10    0.044   0.098           TRUE      36.062049
26      2.536101e-13    0.014   0.057           TRUE      34.782422
27      7.039090e-14    0.066   0.137           TRUE      34.322020
28      7.873702e-13    0.027   0.077           TRUE      32.775540
29      5.116827e-10    0.032   0.080           TRUE      32.658673
30      9.223505e-10    0.082   0.147           TRUE      32.655858
31      3.844297e-16    0.270   0.382           TRUE      31.245598
32      1.973130e-18    0.140   0.247           TRUE      31.216196
33      7.264393e-11    0.069   0.135           TRUE      31.176916
34      7.949843e-12    0.053   0.114           TRUE      29.850350
35      4.999190e-10    0.125   0.200           TRUE      28.229413
36      9.795100e-08    0.051   0.100           TRUE      27.785250
37      7.411156e-16    0.138   0.233           TRUE      26.658016
38      6.298500e-10    0.038   0.087           TRUE      25.441690
39      6.789299e-11    0.026   0.072           TRUE      25.172387
40      1.084779e-11    0.019   0.062           TRUE      24.839213
41      2.030816e-08    0.072   0.131           TRUE      24.371913
42      1.004560e-09    0.020   0.060           TRUE      24.101035
43      1.924047e-18    0.145   0.241           TRUE      24.082050
44      3.561712e-10    0.014   0.051           TRUE      23.505812
45      8.616760e-10    0.022   0.064           TRUE      23.082742
46      1.693342e-03    0.323   0.398           TRUE      22.245884
47      1.129753e-07    0.100   0.164           TRUE      22.094919
48      1.846123e-05    0.094   0.149           TRUE      21.938076
49      2.687633e-07    0.019   0.054           TRUE      21.560609
50      2.237494e-11    0.033   0.083           TRUE      21.442051
51      4.912220e-06    0.207   0.278           TRUE      20.958046
52      1.038754e-07    0.026   0.066           TRUE      20.946831
53      2.083619e-04    0.028   0.061           TRUE      20.874848
54      3.770219e-07    0.023   0.060           TRUE      20.799186
55      1.396314e-09    0.048   0.101           TRUE      20.242445
56      8.650509e-08    0.076   0.134           TRUE      19.691185
57      1.067118e-10    0.024   0.068           TRUE      19.344665
58      5.811928e-10    0.015   0.053           TRUE      19.167141
59      6.225659e-05    0.050   0.092           TRUE      17.820135
60      7.167198e-05    0.066   0.111           TRUE      17.682804
61      3.146696e-05    0.087   0.139           TRUE      17.485600
62      1.895176e-03    0.064   0.106           TRUE      17.261319
63      1.310611e-08    0.032   0.076           TRUE      17.227682
64      3.061914e-08    0.026   0.066           TRUE      17.114455
65      9.725967e-07    0.139   0.206           TRUE      16.976388
66      4.077856e-05    0.027   0.061           TRUE      16.423492
67      8.698939e-05    0.385   0.458           TRUE      16.056556
68      9.459607e-04    0.168   0.223           TRUE      15.904114
69      2.033560e-03    0.090   0.135           TRUE      15.125653
70      2.813741e-03    0.114   0.164           TRUE      14.937964
71      8.009286e-05    0.293   0.360           TRUE      13.674803
72      1.563902e-02    0.039   0.069           TRUE      13.653635
73      1.351762e-03    0.100   0.148           TRUE      13.536046
74      3.701280e-05    0.040   0.078           TRUE      13.375417
75      1.344479e-02    0.211   0.268           TRUE      13.071870
76      5.350543e-05    0.020   0.051           TRUE      12.470204
77      1.956912e-03    0.043   0.079           TRUE      11.868386
78      4.012277e-02    0.120   0.166           TRUE      11.642475
79      1.683174e-02    0.042   0.074           TRUE      11.440897
80      8.163301e-03    0.047   0.081           TRUE      11.193954
81      2.367852e-05    0.072   0.121           TRUE      11.121155
82      2.191334e-04    0.027   0.060           TRUE      10.734090
83      3.803868e-04    0.029   0.061           TRUE       9.780282
84      1.415566e-03    0.026   0.055           TRUE       9.616473
85      4.504183e-03    0.128   0.179           TRUE       9.229553
86      1.448512e-02    0.300   0.366           TRUE       9.101940
87      8.579029e-06    0.054   0.100           TRUE       9.023248
88      9.337767e-03    0.026   0.054           TRUE       8.789141
89      2.169708e-03    0.024   0.052           TRUE       8.750171
90      9.758364e-04    0.074   0.118           TRUE       6.737577
   cluster_support max_cluster_log2FC min_cluster_p_val_adj
1          2;4;5;8          1.3149729          2.926163e-97
2          2;4;5;7          0.7948607          6.914674e-40
3          2;4;6;7          0.9249589          7.845489e-84
4              2;4          0.6745209          9.437479e-26
5              2;4          1.1451353          2.298637e-31
6            2;4;5          1.3935093          1.109563e-12
7                2          1.3424072          1.360686e-14
8                2          0.8193956          1.111942e-41
9             5;11          3.6210213         6.509256e-107
10           2;4;5          1.4041813          4.308952e-23
11           2;3;5          1.8450863         9.231737e-122
12             2;5          2.9027138          2.636680e-36
13             2;5          2.4566705          3.170504e-46
14             3;5          1.4767218          1.459588e-24
15             4;5          0.8428831          7.421299e-05
16             4;7          0.9274611          1.787341e-16
17             2;4          1.6467829          4.940196e-19
18           2;4;5          1.5930094          1.596581e-15
19             5;7          0.4457738          4.973616e-09
20               4          0.4509406          3.927515e-03
21         2;10;11          4.6998013          2.416280e-30
22           2;3;5          0.7505358          1.132269e-13
23             2;5          0.6427965          6.295001e-11
24             2;4          1.1059567          3.210999e-10
25             2;5          1.3852956          1.791840e-09
26             2;4          2.3657208          3.717968e-16
27             4;5          1.1045737          7.269607e-08
28               5          2.5314869          1.754555e-23
29               5          2.4170409          2.764130e-24
30             2;5          1.2350251          4.092195e-12
31            <NA>                 NA                    NA
32           2;5;7          1.1462196          7.985402e-19
33             2;5          1.2749371          7.326753e-11
34            <NA>                 NA                    NA
35               2          1.0222454          1.488441e-06
36               5          1.2771772          1.360718e-03
37               4          0.8293094          1.575930e-15
38               5          2.1796840          5.237064e-23
39               4          1.8819046          5.391534e-23
40            2;10          2.8311254          2.494682e-34
41             2;7          1.0704871          9.315530e-03
42             2;5          2.1459210          1.322867e-14
43          4;8;10          3.4282197          0.000000e+00
44             2;4          1.6265430          2.576288e-05
45               5          2.0470659          3.612157e-14
46             3;7          0.9091691          6.246858e-26
47               7          0.4143896          8.413223e-03
48               4          0.8738634          7.876410e-14
49             2;4          1.8210760          5.930170e-22
50             2;5          1.4127708          2.597650e-07
51               2          0.6580104          6.408539e-05
52             2;4          1.7040296          1.778819e-04
53               2          1.5981382          4.199725e-02
54               5          1.4883684          1.762868e-05
55             2;4          1.6355935          7.396749e-14
56               4          0.8476863          5.142744e-14
57             5;9          1.7112196          4.223296e-08
58               5          2.6165048          6.948591e-35
59               4          1.2404632          1.797973e-15
60            <NA>                 NA                    NA
61               2          0.9192580          2.025225e-02
62               4          0.5470568          1.309821e-03
63             4;5          2.0368111          5.405044e-10
64               5          1.6956866          4.117233e-10
65               2          0.8261983          3.513250e-05
66               2          1.2887431          3.758900e-03
67             3;4          0.5010869          1.400262e-09
68            <NA>                 NA                    NA
69               4          0.2756608          3.954770e-02
70               4          0.7539576          2.823794e-12
71               7          0.7806955          1.070834e-14
72             4;5          1.6322204          4.532332e-05
73               2          1.5494248          1.092159e-25
74            <NA>                 NA                    NA
75             3;7          0.7464233          5.393400e-12
76               5          1.5966198          9.232406e-03
77            <NA>                 NA                    NA
78               5          1.4773086          4.441577e-25
79               4          1.1097092          1.199136e-04
80             2;7          1.2583703          2.484989e-04
81               2          1.4438382          3.915877e-15
82             2;9          1.8534743          4.156685e-04
83            <NA>                 NA                    NA
84               5          1.8828749          5.360613e-06
85               2          0.9005814          1.062043e-05
86             7;8          0.8216365          8.853810e-06
87               4          1.2247618          4.484259e-13
88               5          2.6642721          5.164084e-30
89               2          1.7099427          3.936510e-04
90               4          0.5336785          2.611942e-02

10 Step 12.9: Visualize Top lncRNA Candidates

We visualize the top shared candidates when they exist.

If no shared candidates are found, we visualize the top candidates from the reactive/stress-like state comparison.

top_lncRNAs_for_plot <- priority_astro_lncRNAs %>%
  slice_head(n = 12) %>%
  pull(gene)

if (length(top_lncRNAs_for_plot) == 0) {
  top_lncRNAs_for_plot <- reactive_lncRNA_candidates %>%
    slice_head(n = 12) %>%
    pull(gene)
}

top_lncRNAs_for_plot <- intersect(top_lncRNAs_for_plot, rownames(SO_astro))

top_lncRNAs_for_plot
 [1] "MALAT1"      "NEAT1"       "MIR9-1HG"    "OBI1-AS1"    "SLC44A3-AS1"
 [6] "XIST"        "MIR9-2HG"    "PARD6G-AS1"  "POT1-AS1"    "PCDH9-AS2"  
[11] "UFL1-AS1"    "LINC-PINT"  
if (length(top_lncRNAs_for_plot) > 0) {
  FeaturePlot(
    SO_astro,
    features = top_lncRNAs_for_plot,
    reduction = "umap_astro",
    ncol = 4,
    pt.size = 0.5
  )
} else {
  message("No lncRNA candidates available for FeaturePlot.")
}

if (length(top_lncRNAs_for_plot) > 0) {
  DotPlot(
    SO_astro,
    features = top_lncRNAs_for_plot,
    group.by = "astro_state_refined"
  ) +
    RotatedAxis() +
    labs(title = "Top lncRNA Candidates by Refined Astrocyte State")
} else {
  message("No lncRNA candidates available for DotPlot.")
}

if (length(top_lncRNAs_for_plot) > 0) {
  DotPlot(
    SO_astro,
    features = top_lncRNAs_for_plot,
    group.by = "condition"
  ) +
    RotatedAxis() +
    labs(title = "Top lncRNA Candidates by Condition")
} else {
  message("No lncRNA candidates available for DotPlot.")
}
Warning: Scaling data with a low number of groups may produce misleading
results

11 Step 12.10: Save Astrocyte DE and lncRNA Discovery Results

saveRDS(
  SO_astro,
  file.path(results_dir, "SO_astro_step12_5_fernando_lncRNA_analysis.rds")
)

saveRDS(
  SO_astro_main_DE,
  file.path(results_dir, "SO_astro_step12_5_main_DE_subset.rds")
)

write.csv(
  astro_state_cluster_summary,
  file.path(results_dir, "Step12_5_astro_state_cluster_summary.csv"),
  row.names = FALSE
)

write.csv(
  astro_state_group_summary,
  file.path(results_dir, "Step12_5_astro_state_group_summary.csv"),
  row.names = FALSE
)

write.csv(
  astro_reactive_vs_homeostatic_annotated,
  file.path(results_dir, "Step12_5_DE_reactive_stress_like_PD_vs_homeostatic_like_C.csv"),
  row.names = FALSE
)

write.csv(
  astro_PD_vs_C_annotated,
  file.path(results_dir, "Step12_5_DE_PD_vs_C_astrocytes.csv"),
  row.names = FALSE
)

write.csv(
  astro_cluster_markers_annotated,
  file.path(results_dir, "Step12_5_astro_cluster_markers_annotated.csv"),
  row.names = FALSE
)

write.csv(
  reactive_lncRNA_candidates,
  file.path(results_dir, "Step12_5_reactive_stress_state_lncRNA_candidates.csv"),
  row.names = FALSE
)

write.csv(
  PD_lncRNA_candidates,
  file.path(results_dir, "Step12_5_PD_lncRNA_candidates.csv"),
  row.names = FALSE
)

write.csv(
  cluster_lncRNA_candidates,
  file.path(results_dir, "Step12_5_cluster_lncRNA_candidates.csv"),
  row.names = FALSE
)

write.csv(
  priority_astro_lncRNAs,
  file.path(results_dir, "Step12_5_priority_astro_lncRNA_candidates.csv"),
  row.names = FALSE
)

write.csv(
  driver_lncRNAs,
  file.path(results_dir, "Step12_5_driver_like_lncRNA_candidates.csv"),
  row.names = FALSE
)

write.csv(
  defender_lncRNAs,
  file.path(results_dir, "Step12_5_defender_like_lncRNA_candidates.csv"),
  row.names = FALSE
)

write.csv(
  data.frame(
    setting = c(
      "input_object",
      "state_definition",
      "reactive_stress_like_PD_clusters",
      "homeostatic_like_C_clusters",
      "excluded_from_main_DE_clusters",
      "combined_reactivity_score_usage",
      "min_pct_use",
      "logfc_threshold_use",
      "p_adj_cutoff",
      "lncRNA_logfc_cutoff",
      "n_main_DE_cells",
      "n_reactive_lncRNA_candidates",
      "n_PD_lncRNA_candidates",
      "n_cluster_lncRNA_candidates",
      "n_priority_lncRNAs",
      "n_driver_like_lncRNAs",
      "n_defender_like_lncRNAs"
    ),
    value = c(
      input_path,
      "cluster-based refined astrocyte states",
      paste(reactive_stress_clusters, collapse = ","),
      paste(homeostatic_clusters, collapse = ","),
      paste(c("1", "3", "7", "9", "10", "11"), collapse = ","),
      "z-scored summary/visualization only; not used for main DE grouping",
      min_pct_use,
      logfc_threshold_use,
      p_adj_cutoff,
      lncRNA_logfc_cutoff,
      ncol(SO_astro_main_DE),
      nrow(reactive_lncRNA_candidates),
      nrow(PD_lncRNA_candidates),
      nrow(cluster_lncRNA_candidates),
      nrow(priority_astro_lncRNAs),
      nrow(driver_lncRNAs),
      nrow(defender_lncRNAs)
    )
  ),
  file.path(results_dir, "Step12_5_analysis_settings.csv"),
  row.names = FALSE
)

12 Interpretation Note

This analysis prioritizes lncRNAs that are associated with astrocyte state and/or PD status.

The strongest candidates are not simply the most significant DE genes. They are candidates that satisfy several criteria:

1. lncRNA-like gene annotation or symbol pattern
2. differential expression in cluster-defined reactive/stress-like astrocytes
3. differential expression in PD astrocytes
4. optional support from astrocyte subcluster markers
5. interpretable direction of change

The final candidate list should be treated as a hypothesis-generating result. Any top lncRNA should be checked manually using genome annotation databases and literature before being described as novel or biologically meaningful.