1 Descriptive summary stats by variable

options(width=190)
compareGroups::descrTable(~. , Biok_vert_df, include.miss=TRUE, hide.no = '0', show.all=TRUE)
## 
## --------Summary descriptives table ---------
## 
## _____________________________________________________________ 
##                                                 [ALL]      N  
##                                                 N=218         
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## sex:                                                      218 
##     male                                      82 (37.6%)      
##     female                                   136 (62.4%)      
## age                                          44.3 (12.9)  218 
## BMI                                          28.6 (5.58)  218 
## race:                                                     218 
##     asian                                     3 (1.38%)       
##     black                                     4 (1.83%)       
##     white                                    211 (96.8%)      
## patientno                                    1016 (1365)  218 
## Site_Location:                                            218 
##     Johns Hopkins                             22 (10.1%)      
##     Univeristy of Michigan                    69 (31.7%)      
##     Mayo Clinic                              114 (52.3%)      
##     Pine Rest                                 13 (5.96%)      
## infusionno:                                               218 
##     BL                                        73 (33.5%)      
##     1st                                       72 (33.0%)      
##     3rd                                       73 (33.5%)      
## Blood_Draw_Event:                                         218 
##     Acute Infusion #1 Baseline 100            49 (22.5%)      
##     Acute Infusion #1 Baseline 40             24 (11.0%)      
##     Acute Infusion #1 Stop 100                48 (22.0%)      
##     Acute Infusion #1 Stop 40                 24 (11.0%)      
##     Acute Infusion #3 Stop 100                28 (12.8%)      
##     Acute Infusion #3 Stop 40                 45 (20.6%)      
## Batch_Number                                 3.51 (1.71)  218 
## BSS_Score                                    4.57 (6.82)  213 
## MADRS_Score                                  17.0 (10.6)  217 
## Remission:                                                218 
##     No remission                              77 (35.3%)      
##     Remitter                                 138 (63.3%)      
##     'Missing'                                 3 (1.38%)       
## ResponderANDREMITTER:                                     218 
##     No response                               14 (6.42%)      
##     Responder                                 63 (28.9%)      
##     remission                                138 (63.3%)      
##     'Missing'                                 3 (1.38%)       
## TRP_nM                                       25449 (5942) 218 
## five_HT_nM                                    205 (284)   218 
## KYN_nM                                        917 (244)   218 
## three_HK_nM                                  16.2 (7.44)  218 
## KYNA_nM                                      19.5 (7.68)  218 
## PIC_nM                                       19.2 (13.5)  218 
## Quin_nM                                       146 (43.0)  218 
## AA_nM                                        5.95 (3.12)  218 
## KYN_TRP_ratio                                0.04 (0.01)  218 
## KYN_SER_ratio                                33.2 (72.1)  218 
## QUIN_PIC_ratio                               9.14 (4.39)  218 
## QUIN_KYNA_ratio                              8.30 (3.40)  218 
## threeHK_KYN_ratio                            0.02 (0.01)  218 
## threeHK_KYNA_ratio                           0.91 (0.44)  218 
## IL1B_pg_mL                                   0.28 (0.47)  42  
## IL1B_pg_mL_LLOD                              0.34 (0.19)  218 
## IL2_pg_mL                                    1.27 (6.00)  152 
## IL2_pg_mL_LLOD                               0.92 (5.03)  218 
## IL4_pg_mL                                    0.09 (0.03)  217 
## IL4_pg_mL_LLOD                               0.09 (0.03)  218 
## IL6_pg_mL                                    1.04 (0.58)  218 
## IL8_pg_mL                                    4.36 (1.66)  218 
## IL10_pg_mL                                   0.64 (1.95)  218 
## IL12p70_pg_mL                                 21.8 (186)  217 
## IL12p70_pg_mL_LLOD                            21.7 (185)  218 
## IL13_pg_mL                                   5.07 (11.5)  215 
## IL13_pg_mL_LLOD                              5.01 (11.4)  218 
## TNFa_pg_mL                                   1.44 (0.46)  218 
## IFNy_pg_mL                                   6.97 (5.50)  218 
## CRP_ng_mL                                    2835 (4774)  218 
## NIC_nM                                        41.4 (340)  218 
## NIC_nM_LLOD                                   41.4 (340)  218 
## NTA_nM                                        306 (153)   218 
## SAA_ng_mL                                    2870 (2145)  218 
## VCAM_1_ng_mL                                  309 (67.9)  218 
## ICAM_1_ng_mL                                  308 (82.3)  218 
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

2 Missingness patterns

missingTable(createTable(compareGroups(infusionno ~ ., data = Biok_vert_df, method = NA), hide.no = '0', show.all = TRUE)
)
## 
## --------Missingness table by 'infusionno'---------
## 
## ___________________________________________________________________________ 
##                         [ALL]        BL        1st        3rd     p.overall 
##                         N=218       N=73       N=72       N=73              
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## sex                   0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## age                   0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## BMI                   0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## race                  0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## patientno             0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## Site_Location         0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## Blood_Draw_Event      0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## Sample_ID             0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## Batch_Number          0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## BSS_Score             5 (2.29%)  0 (0.00%)  2 (2.78%)  3 (4.11%)    0.291   
## MADRS_Score           1 (0.46%)  0 (0.00%)  0 (0.00%)  1 (1.37%)    1.000   
## Remission             3 (1.38%)  1 (1.37%)  1 (1.39%)  1 (1.37%)    1.000   
## ResponderANDREMITTER  3 (1.38%)  1 (1.37%)  1 (1.39%)  1 (1.37%)    1.000   
## TRP_nM                0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## five_HT_nM            0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## KYN_nM                0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## three_HK_nM           0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## KYNA_nM               0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## PIC_nM                0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## Quin_nM               0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## AA_nM                 0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## KYN_TRP_ratio         0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## KYN_SER_ratio         0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## QUIN_PIC_ratio        0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## QUIN_KYNA_ratio       0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## threeHK_KYN_ratio     0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## threeHK_KYNA_ratio    0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL1B_pg_mL           176 (80.7%) 57 (78.1%) 61 (84.7%) 58 (79.5%)   0.565   
## IL1B_pg_mL_LLOD       0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL2_pg_mL            66 (30.3%)  28 (38.4%) 20 (27.8%) 18 (24.7%)   0.168   
## IL2_pg_mL_LLOD        0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL4_pg_mL             1 (0.46%)  0 (0.00%)  1 (1.39%)  0 (0.00%)    0.330   
## IL4_pg_mL_LLOD        0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL6_pg_mL             0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL8_pg_mL             0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL10_pg_mL            0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL12p70_pg_mL         1 (0.46%)  0 (0.00%)  1 (1.39%)  0 (0.00%)    0.330   
## IL12p70_pg_mL_LLOD    0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL13_pg_mL            3 (1.38%)  1 (1.37%)  2 (2.78%)  0 (0.00%)    0.327   
## IL13_pg_mL_LLOD       0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## TNFa_pg_mL            0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IFNy_pg_mL            0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## CRP_ng_mL             0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## NIC_nM                0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## NIC_nM_LLOD           0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## NTA_nM                0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## SAA_ng_mL             0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## VCAM_1_ng_mL          0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## ICAM_1_ng_mL          0 (0.00%)  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

3 Outcome visual inspection (MADRS)

# Histogram analysis
ggplot(Biok_vert_df, aes(x=MADRS_Score)) + 
 geom_histogram( colour="black", fill="orange")+
  labs(title="Histogram of MADRS total scores (N=218)")+
  geom_vline(aes(xintercept=mean(MADRS_Score)),
            color="blue", linetype="dashed", size=1)+
  theme_gray()

mu <- ddply(Biok_vert_df, "infusionno", summarise, grp.mean=mean(MADRS_Score))
ggplot(Biok_vert_df, aes(x=MADRS_Score))+
  geom_histogram(color="black", fill="orange")+
  facet_grid(infusionno ~ .)+
  theme(legend.position="none")+
  geom_vline(data=mu, aes(xintercept=grp.mean, color=infusionno),linetype="dashed")+
  labs(title="Distribution of MADRS total score by Ketamine infusion (timepoint)", x="Depressive severity (MADRS)", y="Count")+
  theme_gray()

#Boxplot analysis
mylabs <- levels(Biok_vert_df$infusionno)
library(tidyverse)
Biok_vert_df %>% 
ggplot(aes(x = as.numeric(infusionno), y = MADRS_Score)) + 
  geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 ) +
  ggtitle("Depression by Ketamine Infusion (timeseries)")+
  geom_line(aes(group=patientno, color=Remission)) +
  geom_point(aes(color=Remission))+
  labs(x = "infusionno") +
  scale_x_continuous(breaks = 1:3, labels = mylabs)

4 Histograms by biomarker (whole cohort)

lab<-"Histogram: KP metabolite plasma levels (whole cohort)"
lapply(all_of(vars_KP), function(i) sfsmisc::histBxp(Biok_vert_df[ , i], 
                                                     main = lab , 
                                                     xlab = i,
                                                     col = "gray",
                                                     boxcol = "green",
                                                     medcol = "red"))

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lab<-"Histogram: Inflammatory biomarker plasma levels (whole cohort)"
lapply(all_of(vars_inflam), function(i) sfsmisc::histBxp(Biok_vert_df[ , i], 
                                                     main = lab , 
                                                     xlab = i,
                                                     col = "gray",
                                                     boxcol = "green",
                                                     medcol = "red"))

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lab<-"Histogram: Vascular-Endothelial biomarker plasma levels (whole cohort)"
lapply(all_of(vars_vasc), function(i) sfsmisc::histBxp(Biok_vert_df[ , i], 
                                                     main = lab , 
                                                     xlab = i,
                                                     col = "gray",
                                                     boxcol = "green",
                                                     medcol = "red"))

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# 
# for (scale in c(vars_KP)) {
#         boxplot(Biok_vert_df[, scale] ~ infusionno, data=Biok_vert_df, ylab=scale )
# }
# 
# 
# for (scale in c(vars_vasc)) {
#         boxplot(Biok_vert_df[, scale] ~ infusionno, data=Biok_vert_df, ylab=scale )
# }
# 
# 
# for (scale in c(vars_inflam)) {
#         boxplot(Biok_vert_df[, scale] ~ infusionno, data=Biok_vert_df, ylab=scale )
# }

Biomarkers with potential outliers: NIC_nM, NIC_nM_LLOD, IL1B_pg_mL, IL1B_pg_mL_LLOD, IL2_pg_mL_LLOD, IL12p70_pg_mL, IL12p70_pg_mL_LLOD, IL13_pg_mL, IL13_pg_mL_LLOD

5 KP biomarker boxplots by ketamine infusion no.

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = TRP_nM))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = five_HT_nM))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = KYN_nM))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = three_HK_nM))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = KYNA_nM))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = PIC_nM))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = Quin_nM))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = AA_nM))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = KYN_TRP_ratio))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = KYN_SER_ratio))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = QUIN_PIC_ratio))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = QUIN_KYNA_ratio))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = threeHK_KYN_ratio))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 ) +
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

Potentially problematic observatations: 12, 136

6 Inflammatory biomarker boxplots by ketamine infusion no.

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL1B_pg_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL1B_pg_mL_LLOD))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL2_pg_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL2_pg_mL_LLOD))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL4_pg_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL4_pg_mL_LLOD))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL6_pg_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL8_pg_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL10_pg_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL10_pg_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL12p70_pg_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL12p70_pg_mL_LLOD))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL13_pg_mL))
gg.base +geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IL13_pg_mL_LLOD))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = TNFa_pg_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = IFNy_pg_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = CRP_ng_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

Potentially problematic observations: 16, 106, 3013, 3018, 3008

7 Vascular endothelial biomarker boxplots by ketamine infusion no.

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = NIC_nM))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = NIC_nM_LLOD))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = NTA_nM))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = SAA_ng_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = VCAM_1_ng_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

gg.base <- ggplot(Biok_vert_df, aes(x = infusionno, y = ICAM_1_ng_mL))
gg.base + geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 )+ 
  geom_line(aes(color = Remission, group = patientno))+ geom_point(aes(color=Remission))+
  ggrepel::geom_label_repel(aes(label = patientno),
                  box.padding   = 0.35, 
                  point.padding = 0.5,
                  segment.color = 'grey50') +   ggtitle("Biomarker by Ketamine Infusion (Timeseries)")+   labs(x = "Ketamine Infusion Number") + theme_classic()  

Potentially problematic observations: 96

8 Sensitivity analysis