1 Raw distributions: Demographics/CBC

2 Log distributions: Demo/CBC variables

SG_raw_transformed<-SG_raw %>% select(-Arm, -Sex, -Subject_ID,-Group,-Remission, -Response )
SG_raw_transformed$MONO_BL<-as.numeric(SG_raw_transformed$MONO_BL)

vars_transformed<-c(names(SG_raw_transformed))

#natural log transform
SG_raw_transformed[vars_transformed]<-log(SG_raw_transformed[vars_transformed])

SG_raw_transformed %>% purrr::keep(is.numeric) %>% tidyr::gather() %>%  ggplot(aes(value)) + facet_wrap(~ key, scales = "free") +  geom_density() 

Take home: log transform looks better except for age, HAMD17_BL, HAMD17_WK8

3 KP/Cytokine inspection (RAW)

SMRI_Data_031317 <- read_excel("~/Desktop/SG_SII_SIRI/SMRI_Data_031317.xlsx")
biomarkers_all<-SMRI_Data_031317 %>% dplyr::select(-c(1:15)) %>% dplyr::select(-contains("WK4"))


# Distribution of kynurenines (baseline)
library(gtsummary)

biomarker_KP_BL<-biomarkers_all %>%
  dplyr::select(-contains("WK8")) %>%
  dplyr::select(contains("KP")) %>%
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_KP_BL)) %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

# Distribution of kynurenines (WK8)

biomarker_KP_WK8<-biomarkers_all %>% 
  dplyr::select(-contains("BL")) %>% 
  dplyr::select(contains("KP")) %>% 
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_KP_WK8)) %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

# Distribution of growth factors (BL)
      
biomarker_GF_BL<-biomarkers_all %>% 
  dplyr::select(-contains("WK8")) %>% 
  dplyr::select(contains("GF")) %>% 
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_GF_BL)) %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

# Distribution of growth factors (WK8)

biomarker_GF_WK8<-biomarkers_all%>% 
  dplyr::select(-contains("BL")) %>% 
  dplyr::select(contains("GF")) %>% 
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_GF_WK8)) %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

# Distribution of cytokines (BL)
      
biomarker_CYTOKINES_BL<-biomarkers_all %>% 
  dplyr::select(-contains("WK8")) %>% 
    dplyr::select(-contains("Week8")) %>% 
  dplyr::select(contains("IL"), contains("TNF"), contains("IFN"), contains("CRP"), contains("MCP")) %>% 
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_CYTOKINES_BL)) %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

# Distributions of cytokines (WK8)

biomarker_CYTOKINES_WK8<-biomarkers_all%>% 
  dplyr::select(-contains("BL")) %>% 
  dplyr::select(contains("IL"), contains("TNF"), contains("IFN"), contains("CRP"), contains("MCP")) %>% 
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_CYTOKINES_WK8)) %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

# KP/Cytokines (log transformations)

# Distribution of kynurenines (baseline)
library(gtsummary)

biomarker_KP_BL<-biomarkers_all %>%
  dplyr::select(-contains("WK8")) %>%
  dplyr::select(contains("KP")) %>%
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_KP_BL)) %>% 
        log() %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

# Distribution of kynurenines (WK8)

biomarker_KP_WK8<-biomarkers_all%>% 
  dplyr::select(-contains("BL")) %>% 
  dplyr::select(contains("KP")) %>% 
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_KP_WK8)) %>% 
                log() %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

# Distribution of growth factors (BL)
      
biomarker_GF_BL<-biomarkers_all %>% 
  dplyr::select(-contains("WK8")) %>% 
  dplyr::select(contains("GF")) %>% 
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_GF_BL)) %>% 
                log() %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

# Distribution of growth factors (WK8)

biomarker_GF_WK8<-biomarkers_all %>% 
  dplyr::select(-contains("BL")) %>% 
  dplyr::select(contains("GF")) %>% 
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_GF_WK8)) %>% 
                log() %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

# Distribution of cytokines (BL)
      
biomarker_CYTOKINES_BL<-biomarkers_all%>% 
  dplyr::select(-contains("WK8")) %>% 
    dplyr::select(-contains("Week8")) %>% 
  dplyr::select(contains("IL"), contains("TNF"), contains("IFN"), contains("CRP"), contains("MCP")) %>% 
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_CYTOKINES_BL)) %>% 
                log() %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

# Distributions of cytokines (WK8)

biomarker_CYTOKINES_WK8<-biomarkers_all %>% 
  dplyr::select(-contains("BL")) %>% 
  dplyr::select(contains("IL"), contains("TNF"), contains("IFN"), contains("CRP"), contains("MCP")) %>% 
  names()

      SMRI_Data_031317 %>%
        select(all_of(biomarker_CYTOKINES_WK8)) %>% 
                log() %>% 
        tidyr::gather() %>% 
        ggplot(aes(value)) +
          facet_wrap(~ key, scales = "free") +
          geom_density() 

NOTE: SQRT transformations checked, not as good as log

4 Merging with log-transformed

#making df of KP/inflammatory log transformed markers

SMRI_Data_031317 <- read_excel("~/Desktop/SG_SII_SIRI/SMRI_Data_031317.xlsx")

biomarkers_all<-SMRI_Data_031317 %>%
  dplyr::select(-c(1:15)) %>%
  dplyr::select(-contains("WK4")) %>%
  names()


DF1<-SMRI_Data_031317[,biomarkers_all]+2
DF1_log<-mutate_at(DF1, setNames(biomarkers_all, paste0("log_", biomarkers_all)), log) %>% select(contains("log"))
DF2<-SMRI_Data_031317 %>% select(Subject_ID)
Newdf<-cbind(DF2, DF1_log) 


#making df of CBC/demo transformed markers

SG_bx_transformed<-SG_raw %>% select(-Arm, -Sex, -Age, -Subject_ID,-Group,-Remission, -Response, -HAMD17_BL,-HAMD17_WK8 ) %>% names()

SG_raw_log<-mutate_at(SG_raw, setNames(SG_bx_transformed, paste0("log_", SG_bx_transformed)), log) %>% dplyr::select(Subject_ID, Group,Arm, Sex, Age,  HAMD17_BL,HAMD17_WK8,Remission,Response,contains("log"))


#Merging
combined_df<-merge(SG_raw_log, Newdf, by="Subject_ID", all.x=TRUE, all.y=TRUE) 

createTable(compareGroups(~., data=combined_df))
## 
## --------Summary descriptives table ---------
## 
## __________________________________________ 
##                              [ALL]      N  
##                              N=89          
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## Subject_ID              653492 (941114) 89 
## Group:                                  89 
##     HC                    32 (36.0%)       
##     PT                    57 (64.0%)       
## Arm:                                    57 
##     PBO_ESC               26 (45.6%)       
##     CBX_ESC               31 (54.4%)       
## Sex:                                    87 
##     Male                  46 (52.9%)       
##     Female                41 (47.1%)       
## Age                       41.7 (12.9)   78 
## HAMD17_BL                 24.3 (6.13)   47 
## HAMD17_WK8                11.7 (7.33)   47 
## Remission:                              47 
##     Non-remitter          33 (70.2%)       
##     Remitter              14 (29.8%)       
## Response:                               47 
##     Non-responder         19 (40.4%)       
##     Responder             28 (59.6%)       
## log_BMI                   3.38 (0.22)   75 
## log_PLT_BL                5.44 (0.25)   85 
## log_MONO_BL              -0.78 (0.34)   83 
## log_NEUT_BL               1.27 (0.38)   82 
## log_LYMPH_BL              0.65 (0.26)   83 
## log_PLT_WK8               5.38 (0.26)   52 
## log_MONO_WK8             -0.78 (0.41)   51 
## log_NEUT_WK8              1.30 (0.44)   51 
## log_LYMPH_WK8             0.65 (0.35)   51 
## log_SII_BL                6.06 (0.52)   82 
## log_SII_WK8               6.00 (0.48)   48 
## log_SIRI_BL              -0.15 (0.62)   82 
## log_SIRI_WK8             -0.14 (0.58)   48 
## log_IL1A_BL               0.73 (0.06)   21 
## log_IL1A_WK8              0.71 (0.04)   18 
## log_IL1B_BL               0.78 (0.15)   22 
## log_IL1B_WK8              0.81 (0.16)   18 
## log_IL2_BL                0.82 (0.41)   21 
## log_IL2_WK8               0.85 (0.47)   18 
## log_IL6_BL                1.30 (0.37)   21 
## log_IL6_WK8               1.26 (0.25)   20 
## log_IL8_BL                1.57 (0.58)   21 
## log_IL8_WK8               1.58 (0.76)   18 
## log_IFNG_BL               0.85 (0.31)   21 
## log_IFNG_WK8              0.77 (0.19)   18 
## log_TNFA_BL               1.42 (0.74)   21 
## log_TNFA_WK8              1.51 (0.74)   18 
## log_MCP1_BL               4.63 (0.33)   21 
## log_MCP1_WK8              4.54 (0.57)   18 
## log_CRPSet1_ug_ml_BL      1.64 (0.67)   15 
## log_CRPSet1_ug_ml_WK8     1.53 (0.75)   13 
## log_CRPSet2_µg_ml_BL      1.43 (0.73)   32 
## log_CRPSet2_µg_ml_WK8     1.53 (0.76)   31 
## log_IL1ARaox_7_16_BL      0.85 (0.05)   30 
## log_IL1ARaox_7_16_WK8     0.82 (0.03)   30 
## log_IL1BRaox_7_16_BL      1.12 (0.13)   30 
## log_IL1BRaox_7_16_WK8     1.09 (0.11)   30 
## log_IL2-Raox_7_16_BL      1.50 (0.15)   25 
## log_IL2-Raox_7_16_WK8     1.45 (0.16)   30 
## log_IL6Raox_7_16_BL       1.19 (0.23)   30 
## log_IL6Raox_7_16_WK8      1.16 (0.21)   31 
## log_IL8Raox_7_16_BL       1.89 (0.93)   30 
## log_IL8Raox_7_16_WK8      1.81 (0.90)   30 
## log_IFNGRaox_7_16_BL      0.90 (0.12)   30 
## log_IFNGRaox_7_16_Week8   0.88 (0.09)   30 
## log_TNFARaox_7_16_BL      2.01 (1.40)   30 
## log_TNFARaox_7_16_WK8     1.88 (1.32)   30 
## log_MCP1Raox_7_16_BL      4.46 (0.54)   30 
## log_MCP1Raox_7_16_WK8     4.45 (0.86)   30 
## log_IL4_BL                1.14 (0.31)   26 
## log_IL4_WK8               0.99 (0.27)   18 
## log_IL10_BL               0.90 (0.23)   21 
## log_IL10_WK8              0.94 (0.27)   18 
## log_IL4Raox_7_16_BL       1.53 (0.13)   30 
## log_IL4Raox_7_16_WK8      1.52 (0.16)   30 
## log_IL10Raox_7_16_BL      1.09 (0.22)   30 
## log_IL10Raox_7_16_WK8     1.06 (0.09)   30 
## log_FGF_BL                1.25 (0.43)   15 
## log_FGF_WK8               1.14 (0.58)   9  
## log_VEGF-Elisa_BL         3.61 (0.37)   31 
## log_VEGF-Elisa_WK8        3.68 (0.42)   30 
## log_VEGFRaoxold_BL        3.32 (0.43)   21 
## log_VEGFRaoxold_WK8       3.23 (0.46)   18 
## log_VEGFRaoxnew_BL        2.75 (0.48)   30 
## log_VEGFRaoxnew_WK8       2.69 (0.48)   30 
## log_EGF_BL                1.25 (0.46)   21 
## log_EGF_WK8               1.40 (0.45)   18 
## log_EGFRaox_7_16_BL       1.73 (0.35)   30 
## log_EGFRaox_7_16_WK8      1.64 (0.32)   30 
## log_KP_AA_BL              1.64 (0.35)   43 
## log_KP_AA_WK8             1.70 (0.45)   41 
## log_KP_KynA_BL            2.25 (0.31)   43 
## log_KP_KynA_WK8           2.20 (0.33)   41 
## log_KP_Trp_BL             9.65 (0.23)   43 
## log_KP_Trp_WK8            9.61 (0.23)   41 
## log_KP_Kyn_BL             5.79 (0.33)   43 
## log_KP_Kyn_WK8            5.73 (0.31)   41 
## log_KP_Xan_BL             1.58 (0.31)   42 
## log_KP_Xan_WK8            1.59 (0.35)   37 
## log_KP_Pic_BL             3.05 (0.53)   43 
## log_KP_Pic_WK8            3.05 (0.64)   41 
## log_KP_Quin_BL            4.07 (0.45)   43 
## log_KP_Quin_WK8           4.01 (0.41)   41 
## log_KP_QuinaldA_BL        1.33 (0.30)   43 
## log_KP_QuinaldA_WK8       1.32 (0.27)   41 
## log_KP_3HK_BL             2.86 (0.55)   43 
## log_KP_3HK_WK8            2.79 (0.49)   41 
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

5 Group comparison by patient status

createTable(compareGroups(Group~., data=combined_df))
## 
## --------Summary descriptives table by 'Group'---------
## 
## _______________________________________________________________ 
##                                HC             PT      p.overall 
##                               N=32           N=57               
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## Subject_ID              1806032 (610918) 6452 (2982)   <0.001   
## Arm:                                                      .     
##     PBO_ESC                  0 (.%)       26 (45.6%)            
##     CBX_ESC                  0 (.%)       31 (54.4%)            
## Sex:                                                    0.016   
##     Male                   11 (34.4%)     35 (63.6%)            
##     Female                 21 (65.6%)     20 (36.4%)            
## Age                       39.4 (14.1)    42.7 (12.3)    0.336   
## HAMD17_BL                    . (.)       24.3 (6.13)      .     
## HAMD17_WK8                   . (.)       11.7 (7.33)      .     
## Remission:                                                .     
##     Non-remitter             0 (.%)       33 (70.2%)            
##     Remitter                 0 (.%)       14 (29.8%)            
## Response:                                                 .     
##     Non-responder            0 (.%)       19 (40.4%)            
##     Responder                0 (.%)       28 (59.6%)            
## log_BMI                   3.23 (0.21)    3.43 (0.20)   <0.001   
## log_PLT_BL                5.47 (0.23)    5.42 (0.26)    0.334   
## log_MONO_BL               -0.81 (0.27)   -0.76 (0.38)   0.472   
## log_NEUT_BL               1.21 (0.36)    1.31 (0.38)    0.217   
## log_LYMPH_BL              0.65 (0.24)    0.65 (0.28)    0.914   
## log_PLT_WK8                  . (.)       5.38 (0.26)      .     
## log_MONO_WK8                 . (.)       -0.78 (0.41)     .     
## log_NEUT_WK8                 . (.)       1.30 (0.44)      .     
## log_LYMPH_WK8                . (.)       0.65 (0.35)      .     
## log_SII_BL                6.03 (0.54)    6.08 (0.51)    0.702   
## log_SII_WK8                  . (.)       6.00 (0.48)      .     
## log_SIRI_BL               -0.25 (0.60)   -0.08 (0.62)   0.212   
## log_SIRI_WK8                 . (.)       -0.14 (0.58)     .     
## log_IL1A_BL                  . (.)       0.73 (0.06)      .     
## log_IL1A_WK8                 . (.)       0.71 (0.04)      .     
## log_IL1B_BL                  . (.)       0.78 (0.15)      .     
## log_IL1B_WK8                 . (.)       0.81 (0.16)      .     
## log_IL2_BL                   . (.)       0.82 (0.41)      .     
## log_IL2_WK8                  . (.)       0.85 (0.47)      .     
## log_IL6_BL                   . (.)       1.30 (0.37)      .     
## log_IL6_WK8                  . (.)       1.26 (0.25)      .     
## log_IL8_BL                   . (.)       1.57 (0.58)      .     
## log_IL8_WK8                  . (.)       1.58 (0.76)      .     
## log_IFNG_BL                  . (.)       0.85 (0.31)      .     
## log_IFNG_WK8                 . (.)       0.77 (0.19)      .     
## log_TNFA_BL                  . (.)       1.42 (0.74)      .     
## log_TNFA_WK8                 . (.)       1.51 (0.74)      .     
## log_MCP1_BL                  . (.)       4.63 (0.33)      .     
## log_MCP1_WK8                 . (.)       4.54 (0.57)      .     
## log_CRPSet1_ug_ml_BL         . (.)       1.64 (0.67)      .     
## log_CRPSet1_ug_ml_WK8        . (.)       1.53 (0.75)      .     
## log_CRPSet2_µg_ml_BL         . (.)       1.43 (0.73)      .     
## log_CRPSet2_µg_ml_WK8        . (.)       1.53 (0.76)      .     
## log_IL1ARaox_7_16_BL         . (.)       0.85 (0.05)      .     
## log_IL1ARaox_7_16_WK8        . (.)       0.82 (0.03)      .     
## log_IL1BRaox_7_16_BL         . (.)       1.12 (0.13)      .     
## log_IL1BRaox_7_16_WK8        . (.)       1.09 (0.11)      .     
## log_IL2-Raox_7_16_BL         . (.)       1.50 (0.15)      .     
## log_IL2-Raox_7_16_WK8        . (.)       1.45 (0.16)      .     
## log_IL6Raox_7_16_BL          . (.)       1.19 (0.23)      .     
## log_IL6Raox_7_16_WK8         . (.)       1.16 (0.21)      .     
## log_IL8Raox_7_16_BL          . (.)       1.89 (0.93)      .     
## log_IL8Raox_7_16_WK8         . (.)       1.81 (0.90)      .     
## log_IFNGRaox_7_16_BL         . (.)       0.90 (0.12)      .     
## log_IFNGRaox_7_16_Week8      . (.)       0.88 (0.09)      .     
## log_TNFARaox_7_16_BL         . (.)       2.01 (1.40)      .     
## log_TNFARaox_7_16_WK8        . (.)       1.88 (1.32)      .     
## log_MCP1Raox_7_16_BL         . (.)       4.46 (0.54)      .     
## log_MCP1Raox_7_16_WK8        . (.)       4.45 (0.86)      .     
## log_IL4_BL                   . (.)       1.14 (0.31)      .     
## log_IL4_WK8                  . (.)       0.99 (0.27)      .     
## log_IL10_BL                  . (.)       0.90 (0.23)      .     
## log_IL10_WK8                 . (.)       0.94 (0.27)      .     
## log_IL4Raox_7_16_BL          . (.)       1.53 (0.13)      .     
## log_IL4Raox_7_16_WK8         . (.)       1.52 (0.16)      .     
## log_IL10Raox_7_16_BL         . (.)       1.09 (0.22)      .     
## log_IL10Raox_7_16_WK8        . (.)       1.06 (0.09)      .     
## log_FGF_BL                   . (.)       1.25 (0.43)      .     
## log_FGF_WK8                  . (.)       1.14 (0.58)      .     
## log_VEGF-Elisa_BL            . (.)       3.61 (0.37)      .     
## log_VEGF-Elisa_WK8           . (.)       3.68 (0.42)      .     
## log_VEGFRaoxold_BL           . (.)       3.32 (0.43)      .     
## log_VEGFRaoxold_WK8          . (.)       3.23 (0.46)      .     
## log_VEGFRaoxnew_BL           . (.)       2.75 (0.48)      .     
## log_VEGFRaoxnew_WK8          . (.)       2.69 (0.48)      .     
## log_EGF_BL                   . (.)       1.25 (0.46)      .     
## log_EGF_WK8                  . (.)       1.40 (0.45)      .     
## log_EGFRaox_7_16_BL          . (.)       1.73 (0.35)      .     
## log_EGFRaox_7_16_WK8         . (.)       1.64 (0.32)      .     
## log_KP_AA_BL                 . (.)       1.64 (0.35)      .     
## log_KP_AA_WK8                . (.)       1.70 (0.45)      .     
## log_KP_KynA_BL               . (.)       2.25 (0.31)      .     
## log_KP_KynA_WK8              . (.)       2.20 (0.33)      .     
## log_KP_Trp_BL                . (.)       9.65 (0.23)      .     
## log_KP_Trp_WK8               . (.)       9.61 (0.23)      .     
## log_KP_Kyn_BL                . (.)       5.79 (0.33)      .     
## log_KP_Kyn_WK8               . (.)       5.73 (0.31)      .     
## log_KP_Xan_BL                . (.)       1.58 (0.31)      .     
## log_KP_Xan_WK8               . (.)       1.59 (0.35)      .     
## log_KP_Pic_BL                . (.)       3.05 (0.53)      .     
## log_KP_Pic_WK8               . (.)       3.05 (0.64)      .     
## log_KP_Quin_BL               . (.)       4.07 (0.45)      .     
## log_KP_Quin_WK8              . (.)       4.01 (0.41)      .     
## log_KP_QuinaldA_BL           . (.)       1.33 (0.30)      .     
## log_KP_QuinaldA_WK8          . (.)       1.32 (0.27)      .     
## log_KP_3HK_BL                . (.)       2.86 (0.55)      .     
## log_KP_3HK_WK8               . (.)       2.79 (0.49)      .     
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

6 Group comparison by treatment arm status

createTable(compareGroups(Arm~., data=combined_df))
## 
## --------Summary descriptives table by 'Arm'---------
## 
## ___________________________________________________________ 
##                           PBO_ESC      CBX_ESC    p.overall 
##                             N=26         N=31               
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## Subject_ID              6795 (3022)  6164 (2966)    0.432   
## Group: PT                26 (100%)    31 (100%)       .     
## Sex:                                                0.739   
##     Male                 17 (68.0%)   18 (60.0%)            
##     Female               8 (32.0%)    12 (40.0%)            
## Age                     46.6 (12.5)  39.4 (11.4)    0.033   
## HAMD17_BL               23.4 (6.24)  25.0 (6.08)    0.411   
## HAMD17_WK8              15.0 (7.41)  9.19 (6.33)    0.007   
## Remission:                                          0.004   
##     Non-remitter         19 (95.0%)   14 (51.9%)            
##     Remitter             1 (5.00%)    13 (48.1%)            
## Response:                                           0.040   
##     Non-responder        12 (60.0%)   7 (25.9%)             
##     Responder            8 (40.0%)    20 (74.1%)            
## log_BMI                 3.46 (0.17)  3.42 (0.22)    0.472   
## log_PLT_BL              5.46 (0.30)  5.39 (0.22)    0.353   
## log_MONO_BL             -0.75 (0.43) -0.77 (0.34)   0.808   
## log_NEUT_BL             1.35 (0.41)  1.28 (0.37)    0.522   
## log_LYMPH_BL            0.63 (0.30)  0.67 (0.27)    0.653   
## log_PLT_WK8             5.36 (0.31)  5.39 (0.21)    0.669   
## log_MONO_WK8            -0.74 (0.43) -0.81 (0.39)   0.537   
## log_NEUT_WK8            1.34 (0.52)  1.28 (0.37)    0.624   
## log_LYMPH_WK8           0.63 (0.35)  0.67 (0.35)    0.633   
## log_SII_BL              6.17 (0.52)  6.01 (0.51)    0.258   
## log_SII_WK8             6.05 (0.49)  5.95 (0.47)    0.444   
## log_SIRI_BL             -0.03 (0.66) -0.12 (0.60)   0.598   
## log_SIRI_WK8            -0.02 (0.60) -0.25 (0.56)   0.191   
## log_IL1A_BL             0.75 (0.06)  0.72 (0.06)    0.394   
## log_IL1A_WK8            0.71 (0.04)  0.71 (0.04)    0.869   
## log_IL1B_BL             0.80 (0.15)  0.77 (0.16)    0.617   
## log_IL1B_WK8            0.80 (0.14)  0.81 (0.17)    0.850   
## log_IL2_BL              0.87 (0.50)  0.79 (0.36)    0.710   
## log_IL2_WK8             0.69 (0.00)  0.91 (0.55)    0.170   
## log_IL6_BL              1.43 (0.37)  1.23 (0.37)    0.242   
## log_IL6_WK8             1.24 (0.21)  1.27 (0.27)    0.750   
## log_IL8_BL              1.61 (0.56)  1.55 (0.61)    0.833   
## log_IL8_WK8             1.73 (0.94)  1.53 (0.71)    0.683   
## log_IFNG_BL             0.83 (0.26)  0.86 (0.35)    0.805   
## log_IFNG_WK8            0.69 (0.00)  0.80 (0.21)    0.084   
## log_TNFA_BL             1.46 (0.87)  1.40 (0.70)    0.856   
## log_TNFA_WK8            1.86 (1.25)  1.37 (0.41)    0.432   
## log_MCP1_BL             4.69 (0.35)  4.60 (0.33)    0.533   
## log_MCP1_WK8            4.46 (0.63)  4.57 (0.57)    0.750   
## log_CRPSet1_ug_ml_BL    1.40 (0.36)  1.84 (0.83)    0.206   
## log_CRPSet1_ug_ml_WK8   1.43 (0.81)  1.56 (0.78)    0.807   
## log_CRPSet2_µg_ml_BL    1.44 (0.68)  1.42 (0.77)    0.955   
## log_CRPSet2_µg_ml_WK8   2.09 (0.69)  1.27 (0.65)    0.006   
## log_IL1ARaox_7_16_BL    0.86 (0.07)  0.84 (0.04)    0.276   
## log_IL1ARaox_7_16_WK8   0.83 (0.03)  0.82 (0.03)    0.442   
## log_IL1BRaox_7_16_BL    1.15 (0.14)  1.10 (0.13)    0.398   
## log_IL1BRaox_7_16_WK8   1.16 (0.13)  1.06 (0.09)    0.074   
## log_IL2-Raox_7_16_BL    1.47 (0.13)  1.51 (0.16)    0.479   
## log_IL2-Raox_7_16_WK8   1.48 (0.15)  1.44 (0.16)    0.544   
## log_IL6Raox_7_16_BL     1.17 (0.21)  1.19 (0.25)    0.855   
## log_IL6Raox_7_16_WK8    1.12 (0.21)  1.18 (0.21)    0.498   
## log_IL8Raox_7_16_BL     1.87 (1.07)  1.90 (0.88)    0.942   
## log_IL8Raox_7_16_WK8    1.76 (0.69)  1.82 (0.99)    0.851   
## log_IFNGRaox_7_16_BL    0.94 (0.16)  0.88 (0.09)    0.339   
## log_IFNGRaox_7_16_Week8 0.88 (0.05)  0.88 (0.10)    0.989   
## log_TNFARaox_7_16_BL    1.94 (1.56)  2.04 (1.36)    0.858   
## log_TNFARaox_7_16_WK8   2.12 (1.46)  1.78 (1.28)    0.553   
## log_MCP1Raox_7_16_BL    4.46 (0.47)  4.46 (0.58)    0.992   
## log_MCP1Raox_7_16_WK8   4.44 (0.56)  4.45 (0.97)    0.961   
## log_IL4_BL              1.11 (0.39)  1.16 (0.26)    0.698   
## log_IL4_WK8             1.03 (0.31)  0.97 (0.27)    0.729   
## log_IL10_BL             0.97 (0.24)  0.85 (0.21)    0.261   
## log_IL10_WK8            0.79 (0.22)  1.00 (0.27)    0.136   
## log_IL4Raox_7_16_BL     1.51 (0.10)  1.55 (0.14)    0.427   
## log_IL4Raox_7_16_WK8    1.54 (0.13)  1.51 (0.18)    0.620   
## log_IL10Raox_7_16_BL    1.13 (0.35)  1.08 (0.12)    0.679   
## log_IL10Raox_7_16_WK8   1.07 (0.09)  1.05 (0.09)    0.595   
## log_FGF_BL              1.30 (0.38)  1.20 (0.50)    0.679   
## log_FGF_WK8             0.69 (0.00)  1.27 (0.60)    0.045   
## log_VEGF-Elisa_BL       3.47 (0.28)  3.68 (0.39)    0.087   
## log_VEGF-Elisa_WK8      3.66 (0.46)  3.69 (0.42)    0.850   
## log_VEGFRaoxold_BL      3.38 (0.61)  3.28 (0.30)    0.682   
## log_VEGFRaoxold_WK8     3.29 (0.61)  3.21 (0.41)    0.779   
## log_VEGFRaoxnew_BL      2.71 (0.55)  2.77 (0.46)    0.793   
## log_VEGFRaoxnew_WK8     2.68 (0.56)  2.69 (0.47)    0.970   
## log_EGF_BL              1.33 (0.43)  1.20 (0.49)    0.545   
## log_EGF_WK8             1.45 (0.32)  1.38 (0.50)    0.758   
## log_EGFRaox_7_16_BL     1.82 (0.43)  1.68 (0.30)    0.359   
## log_EGFRaox_7_16_WK8    1.69 (0.29)  1.62 (0.33)    0.562   
## log_KP_AA_BL            1.74 (0.41)  1.57 (0.28)    0.141   
## log_KP_AA_WK8           1.78 (0.48)  1.65 (0.43)    0.370   
## log_KP_KynA_BL          2.23 (0.27)  2.27 (0.34)    0.710   
## log_KP_KynA_WK8         2.12 (0.28)  2.25 (0.36)    0.201   
## log_KP_Trp_BL           9.60 (0.20)  9.69 (0.24)    0.171   
## log_KP_Trp_WK8          9.57 (0.21)  9.64 (0.25)    0.373   
## log_KP_Kyn_BL           5.83 (0.34)  5.76 (0.33)    0.456   
## log_KP_Kyn_WK8          5.78 (0.24)  5.70 (0.35)    0.394   
## log_KP_Xan_BL           1.55 (0.25)  1.61 (0.35)    0.521   
## log_KP_Xan_WK8          1.43 (0.24)  1.70 (0.37)    0.013   
## log_KP_Pic_BL           3.02 (0.61)  3.08 (0.47)    0.754   
## log_KP_Pic_WK8          2.98 (0.76)  3.09 (0.55)    0.622   
## log_KP_Quin_BL          4.17 (0.51)  3.99 (0.39)    0.223   
## log_KP_Quin_WK8         4.05 (0.49)  3.99 (0.36)    0.650   
## log_KP_QuinaldA_BL      1.27 (0.36)  1.37 (0.25)    0.317   
## log_KP_QuinaldA_WK8     1.24 (0.27)  1.38 (0.26)    0.129   
## log_KP_3HK_BL           2.92 (0.51)  2.82 (0.59)    0.555   
## log_KP_3HK_WK8          2.81 (0.51)  2.77 (0.49)    0.813   
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

7 Clinical outcome inspection

SG_df_new_long <- read_excel("~/Desktop/SG_SII_SIRI/SG_df_new_long_05082023.xlsx")
SG_df_new_long <- SG_df_new_long %>% subset(Pt_Group=="TRBDD")
SG_df_new_long$Pt_Group<-as.factor(SG_df_new_long$Pt_Group)
SG_df_new_long$Treatment<-as.factor(SG_df_new_long$Treatment)
SG_df_new_long$Sex<-as.factor(SG_df_new_long$Sex)
SG_df_new_long$Timepoint<-as.factor(SG_df_new_long$Timepoint)

ggplot(SG_df_new_long, aes(x = Timepoint, y = log(HAMD17_total)))+
  geom_boxplot(aes(fill=Timepoint))+
 geom_jitter(width = 0.1)+
  facet_wrap(~Treatment)+
  theme_bw()+   
  theme(legend.position = "none")+
  ggpubr::stat_compare_means(method="t.test", label.y=4)

8 Group comparison by response status

createTable(compareGroups(Response~., data=combined_df))
## 
## --------Summary descriptives table by 'Response'---------
## 
## ____________________________________________________________ 
##                         Non-responder  Responder   p.overall 
##                             N=19          N=28               
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## Subject_ID               6668 (3393)  6101 (2774)    0.550   
## Group: PT                 19 (100%)    28 (100%)       .     
## Arm:                                                 0.040   
##     PBO_ESC              12 (63.2%)    8 (28.6%)             
##     CBX_ESC               7 (36.8%)    20 (71.4%)            
## Sex:                                                 0.271   
##     Male                  9 (47.4%)    19 (67.9%)            
##     Female               10 (52.6%)    9 (32.1%)             
## Age                      45.9 (12.4)  39.9 (11.8)    0.101   
## HAMD17_BL                22.5 (5.65)  25.6 (6.21)    0.084   
## HAMD17_WK8               18.3 (6.31)  7.18 (3.67)   <0.001   
## Remission:                                           0.001   
##     Non-remitter          19 (100%)    14 (50.0%)            
##     Remitter              0 (0.00%)    14 (50.0%)            
## log_BMI                  3.45 (0.19)  3.43 (0.22)    0.689   
## log_PLT_BL               5.38 (0.31)  5.42 (0.22)    0.600   
## log_MONO_BL             -0.63 (0.35)  -0.81 (0.32)   0.108   
## log_NEUT_BL              1.35 (0.32)  1.28 (0.40)    0.541   
## log_LYMPH_BL             0.64 (0.30)  0.65 (0.28)    0.936   
## log_PLT_WK8              5.26 (0.32)  5.43 (0.22)    0.072   
## log_MONO_WK8            -0.63 (0.40)  -0.83 (0.38)   0.117   
## log_NEUT_WK8             1.46 (0.45)  1.25 (0.36)    0.133   
## log_LYMPH_WK8            0.67 (0.36)  0.63 (0.35)    0.729   
## log_SII_BL               6.08 (0.49)  6.06 (0.52)    0.899   
## log_SII_WK8              5.94 (0.51)  6.04 (0.49)    0.549   
## log_SIRI_BL              0.08 (0.52)  -0.17 (0.64)   0.163   
## log_SIRI_WK8             0.05 (0.51)  -0.22 (0.59)   0.134   
## log_IL1A_BL              0.74 (0.06)  0.73 (0.06)    0.727   
## log_IL1A_WK8             0.69 (0.00)  0.72 (0.05)    0.082   
## log_IL1B_BL              0.78 (0.15)  0.79 (0.16)    0.963   
## log_IL1B_WK8             0.76 (0.14)  0.81 (0.17)    0.622   
## log_IL2_BL               0.89 (0.53)  0.79 (0.36)    0.660   
## log_IL2_WK8              0.69 (0.00)  0.91 (0.55)    0.170   
## log_IL6_BL               1.37 (0.38)  1.23 (0.37)    0.458   
## log_IL6_WK8              1.20 (0.25)  1.27 (0.27)    0.638   
## log_IL8_BL               1.82 (0.73)  1.45 (0.49)    0.262   
## log_IL8_WK8              1.84 (1.05)  1.54 (0.70)    0.627   
## log_IFNG_BL              1.00 (0.42)  0.78 (0.23)    0.240   
## log_IFNG_WK8             0.69 (0.00)  0.80 (0.21)    0.084   
## log_TNFA_BL              1.88 (1.18)  1.20 (0.21)    0.182   
## log_TNFA_WK8             2.10 (1.29)  1.35 (0.44)    0.328   
## log_MCP1_BL              4.57 (0.45)  4.66 (0.29)    0.664   
## log_MCP1_WK8             4.18 (0.87)  4.63 (0.46)    0.383   
## log_CRPSet1_ug_ml_BL     1.36 (0.42)  1.80 (0.79)    0.199   
## log_CRPSet1_ug_ml_WK8    1.31 (0.28)  1.50 (0.81)    0.588   
## log_CRPSet2_µg_ml_BL     1.33 (0.81)  1.46 (0.72)    0.672   
## log_CRPSet2_µg_ml_WK8    1.60 (0.90)  1.46 (0.71)    0.692   
## log_IL1ARaox_7_16_BL     0.85 (0.07)  0.84 (0.03)    0.687   
## log_IL1ARaox_7_16_WK8    0.81 (0.03)  0.83 (0.03)    0.427   
## log_IL1BRaox_7_16_BL     1.15 (0.15)  1.10 (0.13)    0.368   
## log_IL1BRaox_7_16_WK8    1.11 (0.11)  1.08 (0.11)    0.529   
## log_IL2-Raox_7_16_BL     1.46 (0.09)  1.52 (0.17)    0.320   
## log_IL2-Raox_7_16_WK8    1.41 (0.11)  1.47 (0.17)    0.284   
## log_IL6Raox_7_16_BL      1.14 (0.21)  1.21 (0.25)    0.433   
## log_IL6Raox_7_16_WK8     1.11 (0.22)  1.18 (0.20)    0.397   
## log_IL8Raox_7_16_BL      2.30 (1.38)  1.69 (0.54)    0.202   
## log_IL8Raox_7_16_WK8     2.17 (1.41)  1.65 (0.55)    0.309   
## log_IFNGRaox_7_16_BL     0.95 (0.17)  0.88 (0.07)    0.230   
## log_IFNGRaox_7_16_Week8  0.88 (0.10)  0.88 (0.09)    0.980   
## log_TNFARaox_7_16_BL     2.70 (1.97)  1.66 (0.89)    0.141   
## log_TNFARaox_7_16_WK8    2.66 (1.97)  1.55 (0.77)    0.137   
## log_MCP1Raox_7_16_BL     4.24 (0.78)  4.58 (0.33)    0.217   
## log_MCP1Raox_7_16_WK8    4.13 (0.91)  4.58 (0.82)    0.225   
## log_IL4_BL               1.21 (0.34)  1.10 (0.30)    0.443   
## log_IL4_WK8              0.96 (0.31)  1.02 (0.27)    0.739   
## log_IL10_BL              0.96 (0.26)  0.85 (0.20)    0.330   
## log_IL10_WK8             0.88 (0.38)  0.98 (0.25)    0.673   
## log_IL4Raox_7_16_BL      1.44 (0.14)  1.58 (0.09)    0.011   
## log_IL4Raox_7_16_WK8     1.47 (0.19)  1.53 (0.15)    0.404   
## log_IL10Raox_7_16_BL     1.09 (0.36)  1.10 (0.11)    0.915   
## log_IL10Raox_7_16_WK8    1.03 (0.08)  1.08 (0.09)    0.163   
## log_FGF_BL               1.47 (0.44)  1.19 (0.40)    0.280   
## log_FGF_WK8              0.70 (0.01)  1.36 (0.60)    0.044   
## log_VEGF-Elisa_BL        3.73 (0.52)  3.56 (0.27)    0.345   
## log_VEGF-Elisa_WK8       3.86 (0.56)  3.60 (0.34)    0.235   
## log_VEGFRaoxold_BL       3.49 (0.60)  3.23 (0.32)    0.307   
## log_VEGFRaoxold_WK8      3.34 (0.67)  3.19 (0.42)    0.695   
## log_VEGFRaoxnew_BL       2.86 (0.69)  2.69 (0.34)    0.493   
## log_VEGFRaoxnew_WK8      2.73 (0.70)  2.67 (0.38)    0.831   
## log_EGF_BL               1.40 (0.42)  1.13 (0.46)    0.203   
## log_EGF_WK8              1.08 (0.46)  1.46 (0.41)    0.201   
## log_EGFRaox_7_16_BL      1.65 (0.28)  1.77 (0.38)    0.321   
## log_EGFRaox_7_16_WK8     1.54 (0.27)  1.69 (0.33)    0.229   
## log_KP_AA_BL             1.68 (0.38)  1.61 (0.32)    0.525   
## log_KP_AA_WK8            1.70 (0.46)  1.70 (0.45)    0.976   
## log_KP_KynA_BL           2.29 (0.34)  2.23 (0.30)    0.559   
## log_KP_KynA_WK8          2.24 (0.33)  2.18 (0.34)    0.583   
## log_KP_Trp_BL            9.61 (0.18)  9.67 (0.25)    0.372   
## log_KP_Trp_WK8           9.62 (0.24)  9.60 (0.23)    0.817   
## log_KP_Kyn_BL            5.81 (0.36)  5.77 (0.31)    0.745   
## log_KP_Kyn_WK8           5.77 (0.24)  5.71 (0.34)    0.532   
## log_KP_Xan_BL            1.59 (0.40)  1.58 (0.25)    0.936   
## log_KP_Xan_WK8           1.57 (0.41)  1.60 (0.31)    0.788   
## log_KP_Pic_BL            3.10 (0.49)  3.02 (0.56)    0.621   
## log_KP_Pic_WK8           3.05 (0.70)  3.05 (0.61)    0.990   
## log_KP_Quin_BL           4.15 (0.51)  4.01 (0.40)    0.339   
## log_KP_Quin_WK8          4.14 (0.44)  3.95 (0.39)    0.174   
## log_KP_QuinaldA_BL       1.38 (0.41)  1.29 (0.19)    0.424   
## log_KP_QuinaldA_WK8      1.35 (0.33)  1.31 (0.23)    0.695   
## log_KP_3HK_BL            2.90 (0.57)  2.83 (0.55)    0.685   
## log_KP_3HK_WK8           2.92 (0.56)  2.72 (0.45)    0.246   
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

9 Group comparison by remission status

createTable(compareGroups(Remission~., data=combined_df))
## 
## --------Summary descriptives table by 'Remission'---------
## 
## ___________________________________________________________ 
##                         Non-remitter   Remitter   p.overall 
##                             N=33         N=14               
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## Subject_ID              6178 (3286)  6689 (2330)    0.550   
## Group: PT                33 (100%)    14 (100%)       .     
## Arm:                                                0.004   
##     PBO_ESC              19 (57.6%)   1 (7.14%)             
##     CBX_ESC              14 (42.4%)   13 (92.9%)            
## Sex:                                                0.451   
##     Male                 18 (54.5%)   10 (71.4%)            
##     Female               15 (45.5%)   4 (28.6%)             
## Age                     42.9 (12.8)  41.0 (11.4)    0.623   
## HAMD17_BL               25.3 (6.49)  22.1 (4.62)    0.064   
## HAMD17_WK8              14.8 (6.35)  4.21 (2.46)   <0.001   
## Response:                                           0.001   
##     Non-responder        19 (57.6%)   0 (0.00%)             
##     Responder            14 (42.4%)   14 (100%)             
## log_BMI                 3.47 (0.17)  3.38 (0.26)    0.255   
## log_PLT_BL              5.39 (0.27)  5.44 (0.22)    0.565   
## log_MONO_BL             -0.74 (0.35) -0.75 (0.34)   0.905   
## log_NEUT_BL             1.32 (0.35)  1.29 (0.43)    0.882   
## log_LYMPH_BL            0.64 (0.30)  0.64 (0.27)    0.924   
## log_PLT_WK8             5.34 (0.29)  5.42 (0.21)    0.305   
## log_MONO_WK8            -0.70 (0.38) -0.88 (0.41)   0.194   
## log_NEUT_WK8            1.38 (0.43)  1.22 (0.33)    0.202   
## log_LYMPH_WK8           0.69 (0.33)  0.54 (0.37)    0.228   
## log_SII_BL              6.06 (0.45)  6.09 (0.63)    0.867   
## log_SII_WK8             5.96 (0.47)  6.08 (0.57)    0.532   
## log_SIRI_BL             -0.06 (0.53) -0.09 (0.78)   0.917   
## log_SIRI_WK8            -0.08 (0.51) -0.21 (0.72)   0.568   
## log_IL1A_BL             0.75 (0.07)  0.71 (0.04)    0.150   
## log_IL1A_WK8            0.70 (0.03)  0.72 (0.05)    0.384   
## log_IL1B_BL             0.77 (0.13)  0.83 (0.22)    0.554   
## log_IL1B_WK8            0.77 (0.12)  0.84 (0.20)    0.444   
## log_IL2_BL              0.79 (0.38)  0.91 (0.53)    0.644   
## log_IL2_WK8             0.86 (0.52)  0.87 (0.47)    0.953   
## log_IL6_BL              1.37 (0.39)  1.07 (0.24)    0.048   
## log_IL6_WK8             1.26 (0.28)  1.24 (0.23)    0.862   
## log_IL8_BL              1.63 (0.55)  1.47 (0.73)    0.635   
## log_IL8_WK8             1.49 (0.70)  1.78 (0.89)    0.482   
## log_IFNG_BL             0.93 (0.36)  0.69 (0.00)    0.028   
## log_IFNG_WK8            0.74 (0.14)  0.84 (0.25)    0.356   
## log_TNFA_BL             1.54 (0.88)  1.20 (0.30)    0.211   
## log_TNFA_WK8            1.56 (0.91)  1.49 (0.53)    0.849   
## log_MCP1_BL             4.68 (0.39)  4.50 (0.18)    0.162   
## log_MCP1_WK8            4.42 (0.65)  4.68 (0.47)    0.350   
## log_CRPSet1_ug_ml_BL    1.54 (0.58)  1.88 (1.00)    0.566   
## log_CRPSet1_ug_ml_WK8   1.55 (0.72)  1.35 (0.85)    0.690   
## log_CRPSet2_µg_ml_BL    1.52 (0.76)  1.21 (0.68)    0.273   
## log_CRPSet2_µg_ml_WK8   1.58 (0.79)  1.35 (0.70)    0.427   
## log_IL1ARaox_7_16_BL    0.84 (0.06)  0.85 (0.02)    0.677   
## log_IL1ARaox_7_16_WK8   0.82 (0.03)  0.83 (0.03)    0.524   
## log_IL1BRaox_7_16_BL    1.11 (0.13)  1.13 (0.15)    0.730   
## log_IL1BRaox_7_16_WK8   1.10 (0.11)  1.08 (0.12)    0.763   
## log_IL2-Raox_7_16_BL    1.46 (0.12)  1.59 (0.19)    0.102   
## log_IL2-Raox_7_16_WK8   1.44 (0.14)  1.48 (0.20)    0.612   
## log_IL6Raox_7_16_BL     1.21 (0.26)  1.13 (0.15)    0.272   
## log_IL6Raox_7_16_WK8    1.16 (0.22)  1.15 (0.19)    0.914   
## log_IL8Raox_7_16_BL     1.93 (1.02)  1.81 (0.73)    0.718   
## log_IL8Raox_7_16_WK8    1.81 (1.00)  1.80 (0.72)    0.976   
## log_IFNGRaox_7_16_BL    0.91 (0.13)  0.87 (0.08)    0.270   
## log_IFNGRaox_7_16_Week8 0.88 (0.08)  0.88 (0.11)    0.860   
## log_TNFARaox_7_16_BL    2.03 (1.52)  1.96 (1.18)    0.889   
## log_TNFARaox_7_16_WK8   1.93 (1.45)  1.78 (1.08)    0.740   
## log_MCP1Raox_7_16_BL    4.44 (0.60)  4.51 (0.36)    0.710   
## log_MCP1Raox_7_16_WK8   4.37 (0.70)  4.61 (1.14)    0.546   
## log_IL4_BL              1.16 (0.33)  1.09 (0.28)    0.615   
## log_IL4_WK8             0.96 (0.28)  1.07 (0.26)    0.425   
## log_IL10_BL             0.88 (0.23)  0.89 (0.22)    0.937   
## log_IL10_WK8            0.94 (0.33)  0.98 (0.19)    0.777   
## log_IL4Raox_7_16_BL     1.50 (0.13)  1.62 (0.09)    0.008   
## log_IL4Raox_7_16_WK8    1.50 (0.15)  1.54 (0.19)    0.625   
## log_IL10Raox_7_16_BL    1.09 (0.25)  1.10 (0.12)    0.885   
## log_IL10Raox_7_16_WK8   1.06 (0.09)  1.07 (0.09)    0.683   
## log_FGF_BL              1.26 (0.48)  1.35 (0.28)    0.667   
## log_FGF_WK8             1.19 (0.70)  1.21 (0.15)    0.965   
## log_VEGF-Elisa_BL       3.64 (0.39)  3.55 (0.31)    0.469   
## log_VEGF-Elisa_WK8      3.74 (0.43)  3.55 (0.40)    0.247   
## log_VEGFRaoxold_BL      3.37 (0.50)  3.20 (0.26)    0.347   
## log_VEGFRaoxold_WK8     3.22 (0.55)  3.23 (0.38)    0.945   
## log_VEGFRaoxnew_BL      2.75 (0.55)  2.74 (0.32)    0.928   
## log_VEGFRaoxnew_WK8     2.70 (0.55)  2.67 (0.35)    0.862   
## log_EGF_BL              1.25 (0.44)  1.16 (0.53)    0.723   
## log_EGF_WK8             1.27 (0.35)  1.51 (0.55)    0.336   
## log_EGFRaox_7_16_BL     1.68 (0.36)  1.83 (0.31)    0.271   
## log_EGFRaox_7_16_WK8    1.59 (0.26)  1.75 (0.40)    0.252   
## log_KP_AA_BL            1.64 (0.39)  1.63 (0.25)    0.882   
## log_KP_AA_WK8           1.76 (0.53)  1.59 (0.21)    0.162   
## log_KP_KynA_BL          2.25 (0.34)  2.25 (0.27)    1.000   
## log_KP_KynA_WK8         2.20 (0.32)  2.20 (0.37)    0.974   
## log_KP_Trp_BL           9.62 (0.21)  9.71 (0.27)    0.273   
## log_KP_Trp_WK8          9.60 (0.23)  9.62 (0.24)    0.803   
## log_KP_Kyn_BL           5.76 (0.34)  5.84 (0.31)    0.501   
## log_KP_Kyn_WK8          5.73 (0.29)  5.74 (0.36)    0.997   
## log_KP_Xan_BL           1.58 (0.35)  1.58 (0.24)    0.992   
## log_KP_Xan_WK8          1.53 (0.33)  1.72 (0.35)    0.125   
## log_KP_Pic_BL           3.08 (0.43)  2.99 (0.70)    0.645   
## log_KP_Pic_WK8          3.10 (0.59)  2.95 (0.73)    0.512   
## log_KP_Quin_BL          4.11 (0.46)  3.97 (0.41)    0.328   
## log_KP_Quin_WK8         4.07 (0.45)  3.91 (0.32)    0.190   
## log_KP_QuinaldA_BL      1.31 (0.34)  1.36 (0.20)    0.488   
## log_KP_QuinaldA_WK8     1.28 (0.27)  1.40 (0.25)    0.179   
## log_KP_3HK_BL           2.86 (0.58)  2.85 (0.51)    0.932   
## log_KP_3HK_WK8          2.77 (0.50)  2.83 (0.49)    0.695   
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

10 Pearson heatmap: TRBDD patients at baseline

list_vars<-combined_df %>% dplyr::select(-Sex, -Arm, -Response, -Subject_ID, -Group) %>% names()
heatmap_df<-combined_df %>% dplyr::select(all_of(list_vars))

heatmap_bl<-heatmap_df %>% select(-contains("WK8"), -contains("Week8")) %>% select(-log_IL2_BL) %>% tidyr::drop_na()
heatmap_bl<-as.matrix(sapply(heatmap_bl, as.numeric)) #IL2BL was problematic so removed

corr <- round(cor(heatmap_bl, use="pairwise.complete.obs"), 2)

ggcorrplot(corr, hc.order = TRUE, type = "lower",
   lab = TRUE, lab_size=1.5, insig="blank", tl.cex=5, title = "Pearson Correlation Matrix (TRBDD cohort at baseline)")

11 Pearson heatmap: TRBDD patients at week 8

list_vars<-combined_df %>% dplyr::select(-Sex, -Arm, -Response, -Subject_ID, -Group) %>% names()
heatmap_df<-combined_df %>% dplyr::select(all_of(list_vars))

heatmap_wk8<-heatmap_df %>% select(-contains("BL")) %>% tidyr::drop_na()
heatmap_wk8<-as.matrix(sapply(heatmap_wk8, as.numeric)) 


corr <- round(cor(heatmap_wk8, use="pairwise.complete.obs"), 2)

ggcorrplot(corr, hc.order = TRUE, type = "lower",
   lab = TRUE, lab_size=1.5, insig="blank", tl.cex=5, title = "Pearson Correlation Matrix (TRBDD cohort at Week 8)")

12 Pearson heatmap: Non-remitters at baseline

list_vars<-combined_df %>% dplyr::select(-Sex, -Arm, -Response, -Subject_ID, -Group) %>% names()
heatmap_df<-combined_df %>% dplyr::select(all_of(list_vars))

heatmap_df_remitters <- heatmap_df[which(heatmap_df$Remission=="Non-remitter"), ] 
heatmap_df_remitters_bl<-heatmap_df_remitters %>% select(contains("BL")) %>% select(-log_IL1A_BL,-log_IL2_BL,-log_IFNG_BL) %>% tidyr::drop_na()
heatmap_df_remitters_bl<-as.matrix(sapply(heatmap_df_remitters_bl, as.numeric)) 

corr <- round(cor(heatmap_df_remitters_bl, use="pairwise.complete.obs"), 2)

ggcorrplot(corr, hc.order = TRUE, type = "lower",
   lab = TRUE, lab_size=1.5, insig="blank", tl.cex=5, title = "Pearson Correlation Matrix (Non-remitters at Baseline)")

13 Pearson heatmap: Remitters at baseline

list_vars<-combined_df %>% dplyr::select(-Sex, -Arm, -Response, -Subject_ID, -Group) %>% names()
heatmap_df<-combined_df %>% dplyr::select(all_of(list_vars))

heatmap_df_remitters <- heatmap_df[which(heatmap_df$Remission=="Remitter"), ] 
heatmap_df_remitters_bl<-heatmap_df_remitters %>% select(contains("BL")) %>% select(-log_IL1A_BL,-log_IL2_BL,-log_IFNG_BL) %>% tidyr::drop_na()
heatmap_df_remitters_bl<-as.matrix(sapply(heatmap_df_remitters_bl, as.numeric)) 

corr <- round(cor(heatmap_df_remitters_bl, use="pairwise.complete.obs"), 2)

ggcorrplot(corr, hc.order = TRUE, type = "lower",
   lab = TRUE, lab_size=1.5, insig="blank", tl.cex=5, title = "Pearson Correlation Matrix (Remitters at Baseline)")

14 Univariate screen by SIRI_BL

list_vars<-combined_df %>% dplyr::select(-Sex, -Remission, -Response, -Subject_ID, -Group) %>% names()
heatmap_df<-combined_df %>% dplyr::select(all_of(list_vars))
heatmap_df <- heatmap_df[which(heatmap_df$Arm!=c("HC")), ] %>% select(-Arm)

gtsummary::tbl_uvregression(
  heatmap_df,
  lm,
  log_SIRI_BL,
  conf.int=TRUE
)
Characteristic N Beta 95% CI1 p-value
Age 48 -0.01 -0.02, 0.01 0.2
HAMD17_BL 43 -0.03 -0.06, 0.00 0.055
HAMD17_WK8 43 0.01 -0.01, 0.03 0.4
log_BMI 47 -0.55 -1.5, 0.44 0.3
log_PLT_BL 50 0.16 -0.52, 0.84 0.6
log_MONO_BL 50 1.2 0.83, 1.5 <0.001
log_NEUT_BL 50 1.4 1.1, 1.6 <0.001
log_LYMPH_BL 50 -0.37 -1.0, 0.27 0.3
log_PLT_WK8 49 0.06 -0.63, 0.75 0.9
log_MONO_WK8 48 0.80 0.41, 1.2 <0.001
log_NEUT_WK8 48 0.77 0.42, 1.1 <0.001
log_LYMPH_WK8 48 0.10 -0.47, 0.67 0.7
log_SII_BL 50 0.92 0.69, 1.1 <0.001
log_SII_WK8 48 0.88 0.59, 1.2 <0.001
log_SIRI_WK8 48 1.0 0.83, 1.1 <0.001
log_IL1A_BL 21 -2.6 -6.4, 1.2 0.2
log_IL1A_WK8 18 -1.5 -9.6, 6.6 0.7
log_IL1B_BL 22 -0.80 -2.3, 0.66 0.3
log_IL1B_WK8 18 -0.27 -2.3, 1.8 0.8
log_IL2_BL 21 0.01 -0.58, 0.61 >0.9
log_IL2_WK8 18 -0.19 -0.86, 0.49 0.6
log_IL6_BL 21 -0.30 -0.93, 0.33 0.3
log_IL6_WK8 20 -0.43 -1.5, 0.69 0.4
log_IL8_BL 21 -0.02 -0.44, 0.40 >0.9
log_IL8_WK8 18 0.09 -0.34, 0.51 0.7
log_IFNG_BL 21 -0.01 -0.79, 0.77 >0.9
log_IFNG_WK8 18 -0.67 -2.4, 1.0 0.4
log_TNFA_BL 21 0.06 -0.27, 0.38 0.7
log_TNFA_WK8 18 0.09 -0.34, 0.53 0.7
log_MCP1_BL 21 -0.92 -1.5, -0.35 0.003
log_MCP1_WK8 18 -0.13 -0.69, 0.43 0.6
log_CRPSet1_ug_ml_BL 15 0.15 -0.35, 0.66 0.5
log_CRPSet1_ug_ml_WK8 13 0.09 -0.34, 0.52 0.7
log_CRPSet2_µg_ml_BL 32 0.08 -0.23, 0.39 0.6
log_CRPSet2_µg_ml_WK8 31 0.07 -0.24, 0.38 0.7
log_IL1ARaox_7_16_BL 30 1.5 -3.4, 6.5 0.5
log_IL1ARaox_7_16_WK8 30 -1.7 -10, 6.8 0.7
log_IL1BRaox_7_16_BL 30 1.0 -0.78, 2.8 0.3
log_IL1BRaox_7_16_WK8 30 1.9 -0.17, 4.0 0.070
log_IL2-Raox_7_16_BL 25 1.6 0.03, 3.2 0.046
log_IL2-Raox_7_16_WK8 30 0.47 -1.1, 2.0 0.5
log_IL6Raox_7_16_BL 30 -0.17 -1.2, 0.86 0.7
log_IL6Raox_7_16_WK8 31 -0.04 -1.2, 1.1 >0.9
log_IL8Raox_7_16_BL 30 -0.09 -0.35, 0.17 0.5
log_IL8Raox_7_16_WK8 30 0.07 -0.20, 0.34 0.6
log_IFNGRaox_7_16_BL 30 0.76 -1.3, 2.8 0.5
log_IFNGRaox_7_16_Week8 30 0.45 -2.3, 3.2 0.7
log_TNFARaox_7_16_BL 30 -0.02 -0.19, 0.16 0.8
log_TNFARaox_7_16_WK8 30 0.09 -0.09, 0.27 0.3
log_MCP1Raox_7_16_BL 30 -0.32 -0.75, 0.12 0.15
log_MCP1Raox_7_16_WK8 30 -0.24 -0.51, 0.03 0.075
log_IL4_BL 26 -0.65 -1.3, 0.04 0.063
log_IL4_WK8 18 0.17 -1.0, 1.3 0.8
log_IL10_BL 21 0.35 -0.70, 1.4 0.5
log_IL10_WK8 18 -0.74 -1.9, 0.38 0.2
log_IL4Raox_7_16_BL 30 -1.5 -3.3, 0.34 0.11
log_IL4Raox_7_16_WK8 30 -0.47 -1.9, 1.0 0.5
log_IL10Raox_7_16_BL 30 -0.60 -1.7, 0.49 0.3
log_IL10Raox_7_16_WK8 30 -2.3 -4.9, 0.37 0.090
log_FGF_BL 15 0.16 -0.63, 0.95 0.7
log_FGF_WK8 9 0.02 -0.75, 0.80 >0.9
log_VEGF-Elisa_BL 31 -0.31 -0.94, 0.32 0.3
log_VEGF-Elisa_WK8 30 -0.21 -0.78, 0.36 0.4
log_VEGFRaoxold_BL 21 -0.33 -0.86, 0.21 0.2
log_VEGFRaoxold_WK8 18 -0.11 -0.81, 0.59 0.7
log_VEGFRaoxnew_BL 30 -0.24 -0.73, 0.26 0.3
log_VEGFRaoxnew_WK8 30 -0.13 -0.63, 0.37 0.6
log_EGF_BL 21 -0.17 -0.69, 0.35 0.5
log_EGF_WK8 18 -0.32 -1.0, 0.37 0.3
log_EGFRaox_7_16_BL 30 0.02 -0.67, 0.72 >0.9
log_EGFRaox_7_16_WK8 30 0.21 -0.55, 1.0 0.6
log_KP_AA_BL 39 0.39 -0.17, 1.0 0.2
log_KP_AA_WK8 37 0.08 -0.37, 0.53 0.7
log_KP_KynA_BL 39 0.06 -0.57, 0.69 0.9
log_KP_KynA_WK8 37 -0.09 -0.70, 0.51 0.8
log_KP_Trp_BL 39 -0.11 -1.0, 0.76 0.8
log_KP_Trp_WK8 37 -0.35 -1.2, 0.51 0.4
log_KP_Kyn_BL 39 0.27 -0.35, 0.90 0.4
log_KP_Kyn_WK8 37 -0.07 -0.71, 0.58 0.8
log_KP_Xan_BL 38 0.11 -0.54, 0.77 0.7
log_KP_Xan_WK8 33 -0.35 -0.94, 0.25 0.2
log_KP_Pic_BL 39 0.26 -0.18, 0.69 0.2
log_KP_Pic_WK8 37 0.29 -0.03, 0.62 0.078
log_KP_Quin_BL 39 0.32 -0.12, 0.76 0.15
log_KP_Quin_WK8 37 0.24 -0.25, 0.73 0.3
log_KP_QuinaldA_BL 39 0.46 -0.20, 1.1 0.2
log_KP_QuinaldA_WK8 37 0.50 -0.23, 1.2 0.2
log_KP_3HK_BL 39 -0.24 -0.60, 0.11 0.2
log_KP_3HK_WK8 37 -0.15 -0.56, 0.27 0.5
1 CI = Confidence Interval

15 SIRI by timepoint and remission

ggplot(SG_df_new_long, aes(x = Timepoint, y = log(SIRI)))+
  geom_boxplot(aes(fill=Timepoint))+
 geom_jitter(width = 0.1)+
  facet_wrap(~Treatment)+
  theme_bw()+   
  theme(legend.position = "none")+
  ggpubr::stat_compare_means(method="t.test", label.y=4)

ggplot(SG_df_new_long, aes(x = Timepoint, y = log(SIRI)))+
  geom_boxplot(aes(fill=Timepoint))+
 geom_jitter(width = 0.1)+
  facet_wrap(~Remission)+
  theme_bw()+   
  theme(legend.position = "none")+
  ggpubr::stat_compare_means(method="t.test", label.y=4)

16 MODEL 1: SIRI by HAMD17*Timepoint

17 MODEL 2: HAMD17_WK8 by SIRI_BL

# SII_model<-lm(HAMD17_WK8~Arm+HAMD17_BL+log(SII_BL), data=combined_df)
# sjPlot::tab_model(SII_model)

SIRI_model<-lm(HAMD17_WK8~Sex+Age+log_BMI+Arm+HAMD17_BL+log_SIRI_BL, data=combined_df)
sjPlot::tab_model(SIRI_model)
  HAMD 17 WK 8
Predictors Estimates CI p
(Intercept) -15.64 -56.10 – 24.83 0.438
Sex [Female] 4.39 0.15 – 8.63 0.043
Age 0.12 -0.06 – 0.29 0.198
log BMI 4.61 -6.91 – 16.14 0.422
Arm [CBX ESC] -5.30 -9.89 – -0.71 0.025
HAMD17 BL 0.34 -0.02 – 0.69 0.061
log SIRI BL 2.48 -1.34 – 6.29 0.196
Observations 43
R2 / R2 adjusted 0.352 / 0.244

18 MODEL 3: HAMD17_WK8 by SIRI_BL*interaction

# SII_model_interaction<-lm(HAMD17_WK8~Arm+HAMD17_BL+SII_BL*Age, data=combined_df)
# # plot(SII_model_interaction, which=c(2,6))
# sjPlot::tab_model(SII_model_interaction)
# reg_cohend(SII_model_interaction)
# interactions::interact_plot(SII_model_interaction, pred = SII_BL, modx = Age, jitter=0.1, plot.points = TRUE,  main.title = "Tx outcomes linked to baseline SII-to-Age interaction")

SIRI_model_interaction<-lm(HAMD17_WK8~Sex+Age+log_BMI+Arm+HAMD17_BL*log_SIRI_BL, data=combined_df)
# plot(SII_model_interaction, which=c(2,6))
sjPlot::tab_model(SIRI_model_interaction)
  HAMD 17 WK 8
Predictors Estimates CI p
(Intercept) -10.29 -47.75 – 27.17 0.581
Sex [Female] 6.02 1.93 – 10.11 0.005
Age 0.05 -0.12 – 0.22 0.525
log BMI 3.31 -7.35 – 13.96 0.533
Arm [CBX ESC] -5.13 -9.36 – -0.90 0.019
HAMD17 BL 0.42 0.09 – 0.75 0.014
log SIRI BL -17.85 -33.26 – -2.44 0.024
HAMD17 BL * log SIRI BL 0.91 0.24 – 1.59 0.009
Observations 43
R2 / R2 adjusted 0.467 / 0.361

19 MODEL 4 (reduced/final): HAMD17_WK8 by SIRI_BL*interaction

# SII_model_interaction<-lm(HAMD17_WK8~Arm+HAMD17_BL+SII_BL*Age, data=combined_df)
# # plot(SII_model_interaction, which=c(2,6))
# sjPlot::tab_model(SII_model_interaction)
# reg_cohend(SII_model_interaction)
# interactions::interact_plot(SII_model_interaction, pred = SII_BL, modx = Age, jitter=0.1, plot.points = TRUE,  main.title = "Tx outcomes linked to baseline SII-to-Age interaction")

SII_model_interaction<-lm(HAMD17_WK8~Sex+Age+Arm+HAMD17_BL*log_SIRI_BL, data=combined_df)
# plot(SII_model_interaction, which=c(2,6))
sjPlot::tab_model(SIRI_model_interaction)
  HAMD 17 WK 8
Predictors Estimates CI p
(Intercept) -10.29 -47.75 – 27.17 0.581
Sex [Female] 6.02 1.93 – 10.11 0.005
Age 0.05 -0.12 – 0.22 0.525
log BMI 3.31 -7.35 – 13.96 0.533
Arm [CBX ESC] -5.13 -9.36 – -0.90 0.019
HAMD17 BL 0.42 0.09 – 0.75 0.014
log SIRI BL -17.85 -33.26 – -2.44 0.024
HAMD17 BL * log SIRI BL 0.91 0.24 – 1.59 0.009
Observations 43
R2 / R2 adjusted 0.467 / 0.361
interactions::interact_plot(SIRI_model_interaction, pred = log_SIRI_BL, modx = Age, jitter=0.1, plot.points = TRUE,  main.title = "Tx outcomes linked to baseline SIRI-to-Age interaction")