Descriptive summary of source datafile

Descriptive summary stats by variable (long format)

options(width=190)
compareGroups::descrTable(~. , data = Biok_vert_df, hide.no = '0')
## 
## --------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:                                                215 
##     No remission                              77 (35.8%)      
##     Remitter                                 138 (64.2%)      
## 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 
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

Missingness counts per variable

M<- sapply(Biok_vert_df, function(x) sum(is.na(x))); M[M>0]
##     BSS_Score   MADRS_Score     Remission    IL1B_pg_mL     IL2_pg_mL     IL4_pg_mL IL12p70_pg_mL    IL13_pg_mL 
##             5             1             3           176            66             1             1             3

Note: IL1B_pg_mL has really high missingness count.

Descriptive summary stats by infusion number (long format)

createTable(compareGroups(infusionno ~ ., data = Biok_vert_df, method = NA), hide.no = '0', show.p.mul    = T)
## 
## --------Summary descriptives table by 'infusionno'---------
## 
## ______________________________________________________________________________________________________________________________________________ 
##                                                     BL              1st              3rd        p.overall p.BL vs 1st p.BL vs 3rd p.1st vs 3rd 
##                                                    N=73             N=72             N=73                                                      
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## sex:                                                                                              0.909      1.000       1.000       1.000     
##     male                                        26 (35.6%)       28 (38.9%)       28 (38.4%)                                                   
##     female                                      47 (64.4%)       44 (61.1%)       45 (61.6%)                                                   
## age                                          46.0 [33.0;55.0] 47.0 [34.5;55.0] 47.0 [35.0;55.0]   0.977      0.916       0.916       0.916     
## BMI                                          28.1 [24.9;32.3] 28.1 [24.7;31.6] 28.1 [24.9;31.7]   0.992      0.969       0.969       0.969     
## race:                                                                                             1.000      1.000       1.000       1.000     
##     asian                                       1 (1.37%)        1 (1.39%)        1 (1.37%)                                                    
##     black                                       2 (2.74%)        1 (1.39%)        1 (1.37%)                                                    
##     white                                       70 (95.9%)       70 (97.2%)       71 (97.3%)                                                   
## patientno                                    125 [97.0;3006]  126 [97.8;3005]  125 [97.0;3005]    0.993      0.956       0.956       0.956     
## Site_Location:                                                                                    1.000      1.000       1.000       1.000     
##     Johns Hopkins                               7 (9.59%)        7 (9.72%)        8 (11.0%)                                                    
##     Univeristy of Michigan                      23 (31.5%)       23 (31.9%)       23 (31.5%)                                                   
##     Mayo Clinic                                 38 (52.1%)       38 (52.8%)       38 (52.1%)                                                   
##     Pine Rest                                   5 (6.85%)        4 (5.56%)        4 (5.48%)                                                    
## Blood_Draw_Event:                                                                                <0.001     <0.001      <0.001       <0.001    
##     Acute Infusion #1 Baseline 100              49 (67.1%)       0 (0.00%)        0 (0.00%)                                                    
##     Acute Infusion #1 Baseline 40               24 (32.9%)       0 (0.00%)        0 (0.00%)                                                    
##     Acute Infusion #1 Stop 100                  0 (0.00%)        48 (66.7%)       0 (0.00%)                                                    
##     Acute Infusion #1 Stop 40                   0 (0.00%)        24 (33.3%)       0 (0.00%)                                                    
##     Acute Infusion #3 Stop 100                  0 (0.00%)        0 (0.00%)        28 (38.4%)                                                   
##     Acute Infusion #3 Stop 40                   0 (0.00%)        0 (0.00%)        45 (61.6%)                                                   
## Batch_Number                                 4.00 [2.00;5.00] 3.50 [2.00;5.00] 3.00 [2.00;5.00]   0.978      0.981       0.981       0.981     
## BSS_Score                                    7.00 [1.00;13.0] 0.00 [0.00;2.00] 0.00 [0.00;1.00]  <0.001     <0.001      <0.001       0.242     
## MADRS_Score                                  27.0 [24.0;32.0] 13.5 [8.00;19.0] 6.00 [4.00;12.2]  <0.001     <0.001      <0.001       <0.001    
## Remission:                                                                                        0.992      1.000       1.000       1.000     
##     No remission                                26 (36.1%)       25 (35.2%)       26 (36.1%)                                                   
##     Remitter                                    46 (63.9%)       46 (64.8%)       46 (63.9%)                                                   
## TRP_nM                                         27561 (5740)     24360 (5841)     24412 (5747)     0.001      0.003       0.003       0.998     
## five_HT_nM                                   75.7 [31.9;296]  77.5 [28.9;256]  73.0 [21.0;292]    0.542      0.693       0.693       0.716     
## KYN_nM                                        936 [826;1149]   861 [743;999]    861 [729;997]     0.027      0.031       0.031       0.972     
## three_HK_nM                                  14.9 [12.6;19.4] 13.9 [12.1;17.4] 14.0 [11.8;17.8]   0.199      0.196       0.196       0.968     
## KYNA_nM                                      19.7 [14.3;24.2] 18.3 [14.2;22.8] 17.1 [13.7;23.0]   0.485      0.626       0.626       0.719     
## PIC_nM                                       17.4 [12.8;24.4] 15.6 [12.4;21.4] 17.1 [13.4;22.6]   0.365      0.453       0.491       0.491     
## Quin_nM                                       141 [112;175]    134 [106;174]    141 [113;172]     0.874      0.902       0.902       0.902     
## AA_nM                                        5.29 [4.31;6.90] 5.38 [4.09;7.01] 5.05 [4.09;6.74]   0.552      0.934       0.592       0.592     
## KYN_TRP_ratio                                0.04 [0.03;0.04] 0.04 [0.03;0.04] 0.04 [0.03;0.04]   0.634      0.785       0.785       0.785     
## KYN_SER_ratio                                12.1 [2.85;28.9] 12.4 [3.95;33.2] 13.9 [3.43;39.4]   0.771      0.770       0.770       0.770     
## QUIN_PIC_ratio                               7.60 [5.75;10.6] 7.86 [6.52;10.9] 8.64 [6.01;11.6]   0.547      0.567       0.567       0.978     
## QUIN_KYNA_ratio                              7.42 [5.62;9.33] 7.63 [5.86;9.10] 7.81 [6.05;10.5]   0.591      0.716       0.716       0.716     
## threeHK_KYN_ratio                            0.02 [0.01;0.02] 0.02 [0.01;0.02] 0.02 [0.01;0.02]   0.924      0.856       0.856       0.856     
## threeHK_KYNA_ratio                           0.80 [0.64;1.09] 0.78 [0.64;1.01] 0.80 [0.62;1.06]   0.897      0.853       0.853       0.853     
## IL1B_pg_mL                                   0.11 [0.08;0.24] 0.17 [0.13;0.27] 0.16 [0.10;0.27]   0.489      0.523       0.523       0.856     
## IL1B_pg_mL_LLOD                              0.32 [0.32;0.32] 0.32 [0.32;0.32] 0.32 [0.32;0.32]   0.871      0.989       0.989       0.989     
## IL2_pg_mL                                    0.45 [0.30;0.63] 0.38 [0.26;0.52] 0.38 [0.29;0.56]   0.421      0.521       0.521       0.521     
## IL2_pg_mL_LLOD                               0.26 [0.10;0.49] 0.28 [0.10;0.42] 0.31 [0.10;0.48]   0.540      0.815       0.602       0.602     
## IL4_pg_mL                                    0.08 [0.07;0.10] 0.09 [0.07;0.10] 0.09 [0.07;0.10]   0.898      0.821       0.821       0.821     
## IL4_pg_mL_LLOD                               0.08 [0.07;0.10] 0.09 [0.07;0.10] 0.09 [0.07;0.10]   0.891      0.899       0.899       0.899     
## IL6_pg_mL                                    0.83 [0.69;1.19] 0.93 [0.66;1.32] 0.85 [0.64;1.11]   0.423      0.520       0.520       0.520     
## IL8_pg_mL                                    4.48 [3.47;5.24] 4.41 [3.42;5.32] 3.86 [3.04;4.57]   0.040      0.812       0.057       0.057     
## IL10_pg_mL                                   0.34 [0.27;0.43] 0.36 [0.29;0.45] 0.38 [0.28;0.44]   0.724      0.814       0.814       0.893     
## IL12p70_pg_mL                                0.37 [0.30;0.49] 0.40 [0.30;0.49] 0.40 [0.30;0.48]   0.893      0.818       0.818       0.818     
## IL12p70_pg_mL_LLOD                           0.37 [0.30;0.49] 0.39 [0.30;0.49] 0.40 [0.30;0.48]   0.880      0.934       0.934       0.934     
## IL13_pg_mL                                   3.56 [3.15;4.12] 3.64 [3.16;4.21] 3.63 [3.22;4.05]   0.906      0.888       0.888       0.888     
## IL13_pg_mL_LLOD                              3.55 [3.13;4.10] 3.64 [3.15;4.19] 3.63 [3.22;4.05]   0.909      0.881       0.881       0.881     
## TNFa_pg_mL                                   1.39 [1.21;1.63] 1.31 [1.17;1.58] 1.34 [1.17;1.58]   0.672      0.791       0.791       0.797     
## IFNy_pg_mL                                   5.26 [4.14;7.52] 5.17 [4.06;7.07] 5.49 [4.27;7.54]   0.549      0.657       0.657       0.657     
## CRP_ng_mL                                    1246 [538;3014]  1094 [460;2863]  1289 [424;2822]    0.902      0.968       0.968       0.968     
## NIC_nM                                       0.56 [0.32;0.98] 0.51 [0.35;1.34] 0.51 [0.34;0.98]   0.876      0.874       0.874       0.874     
## NIC_nM_LLOD                                  0.56 [0.32;0.98] 0.51 [0.35;1.34] 0.51 [0.34;0.98]   0.876      0.874       0.874       0.874     
## NTA_nM                                        297 [213;429]    280 [194;391]    285 [194;330]     0.243      0.415       0.314       0.517     
## SAA_ng_mL                                    2191 [1207;4154] 2265 [1246;3934] 2131 [1353;4145]   0.988      0.987       0.987       0.987     
## VCAM_1_ng_mL                                    313 (66.6)       309 (66.1)       305 (71.5)      0.776      0.949       0.758       0.916     
## ICAM_1_ng_mL                                  295 [258;358]    285 [256;364]    284 [252;344]     0.717      0.675       0.675       0.675     
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

Note: If this is unreadable I can send an excel. Dont pay too much attention to p-values at this stage, but KYN and IL8 may distinguish infusionno

Descriptive summary of variables (wide format)

Outcome inspection: MADRS_Score variable

outcome_parent<-lm(MADRS_Score~sex+age+BMI, data=Biok_vert_df)
outcome_infusion<-lm(MADRS_Score_3rd~sex+age+BMI+MADRS_Score_BL, data=Biok_wide)

hist(Biok_vert_df$MADRS_Score, main="MADRS_Score (parent distribution)", xlab="MADRS total Score")

autoplot(outcome_parent, which=c(2,6))

hist(Biok_wide$MADRS_Score_3rd, main="MADRS_Score (infusionno #3 distribution)", xlab="MADRS total score")

autoplot(outcome_infusion, which=c(2,6))

Will hold off on transforming outcome until modelling stage

Inspection of residuals and coefficients of raw and transformed biomarkers

Biomarker VIF Beta_coeff T_test Std_error p_value R_coeff
AA_nM_1st AA_nM_1st 1.27 1.81 1.05 1.73 0.30 0.11
AA_nM_3rd AA_nM_3rd 1.20 1.73 0.96 1.80 0.34 0.10
AA_nM_BL AA_nM_BL 1.21 2.24 1.29 1.74 0.20 0.15
CRP_ng_mL_1st CRP_ng_mL_1st 1.20 1.37 0.78 1.76 0.44 0.09
CRP_ng_mL_3rd CRP_ng_mL_3rd 1.27 1.79 0.99 1.80 0.33 0.09
CRP_ng_mL_BL CRP_ng_mL_BL 1.19 1.79 1.00 1.79 0.32 0.10
five_HT_nM_1st five_HT_nM_1st 1.09 1.11 0.64 1.72 0.52 0.13
five_HT_nM_3rd five_HT_nM_3rd 1.17 1.38 0.80 1.73 0.43 0.17
five_HT_nM_BL five_HT_nM_BL 1.08 1.50 0.87 1.73 0.39 0.16
ICAM_1_ng_mL_1st ICAM_1_ng_mL_1st 1.05 1.67 0.97 1.72 0.34 0.10
ICAM_1_ng_mL_3rd ICAM_1_ng_mL_3rd 1.05 2.22 1.25 1.77 0.21 0.11
ICAM_1_ng_mL_BL ICAM_1_ng_mL_BL 1.07 2.30 1.27 1.80 0.21 0.10
IFNy_pg_mL_1st IFNy_pg_mL_1st 1.06 1.49 0.86 1.73 0.39 0.10
IFNy_pg_mL_3rd IFNy_pg_mL_3rd 1.06 1.97 1.10 1.79 0.27 0.09
IFNy_pg_mL_BL IFNy_pg_mL_BL 1.08 1.90 1.06 1.78 0.29 0.10
IL10_pg_mL_1st IL10_pg_mL_1st 1.02 1.81 1.05 1.73 0.30 0.11
IL10_pg_mL_3rd IL10_pg_mL_3rd 1.02 2.24 1.26 1.78 0.21 0.11
IL10_pg_mL_BL IL10_pg_mL_BL 1.02 2.30 1.29 1.78 0.20 0.12
IL12p70_pg_mL_1st IL12p70_pg_mL_1st 1.12 1.32 0.73 1.80 0.47 0.09
IL12p70_pg_mL_3rd IL12p70_pg_mL_3rd 1.11 2.14 1.18 1.81 0.24 0.09
IL12p70_pg_mL_BL IL12p70_pg_mL_BL 1.11 2.14 1.18 1.81 0.24 0.09
IL13_pg_mL_1st IL13_pg_mL_1st 1.13 1.50 0.83 1.80 0.41 0.10
IL13_pg_mL_3rd IL13_pg_mL_3rd 1.12 2.12 1.17 1.81 0.25 0.09
IL13_pg_mL_BL IL13_pg_mL_BL 1.13 1.91 1.04 1.84 0.30 0.08
IL1B_pg_mL_1st IL1B_pg_mL_1st 1.39 -1.79 -0.47 3.83 0.66 0.16
IL1B_pg_mL_3rd IL1B_pg_mL_3rd 1.64 -0.79 -0.16 4.91 0.88 0.26
IL1B_pg_mL_BL IL1B_pg_mL_BL 1.29 -3.36 -1.26 2.66 0.23 0.39
IL2_pg_mL_1st IL2_pg_mL_1st 1.06 -1.09 -0.62 1.76 0.54 0.17
IL2_pg_mL_3rd IL2_pg_mL_3rd 1.07 -0.13 -0.07 1.83 0.94 0.12
IL2_pg_mL_BL IL2_pg_mL_BL 1.08 -1.35 -0.68 1.98 0.50 0.19
IL4_pg_mL_1st IL4_pg_mL_1st 1.10 1.12 0.63 1.78 0.53 0.09
IL4_pg_mL_3rd IL4_pg_mL_3rd 1.07 1.98 1.10 1.80 0.27 0.09
IL4_pg_mL_BL IL4_pg_mL_BL 1.14 1.90 1.06 1.80 0.29 0.09
IL6_pg_mL_1st IL6_pg_mL_1st 1.05 1.48 0.85 1.74 0.40 0.09
IL6_pg_mL_3rd IL6_pg_mL_3rd 1.42 1.85 1.01 1.83 0.32 0.09
IL6_pg_mL_BL IL6_pg_mL_BL 1.31 2.25 1.22 1.84 0.23 0.09
IL8_pg_mL_1st IL8_pg_mL_1st 1.14 1.34 0.77 1.74 0.44 0.10
IL8_pg_mL_3rd IL8_pg_mL_3rd 1.04 2.06 1.15 1.79 0.25 0.09
IL8_pg_mL_BL IL8_pg_mL_BL 1.08 2.06 1.13 1.81 0.26 0.09
KYN_nM_1st KYN_nM_1st 1.33 2.00 1.12 1.77 0.27 0.10
KYN_nM_3rd KYN_nM_3rd 1.29 3.02 1.64 1.84 0.11 0.13
KYN_nM_BL KYN_nM_BL 1.27 2.55 1.41 1.81 0.16 0.11
KYN_SER_ratio_1st KYN_SER_ratio_1st 1.06 1.56 0.91 1.72 0.37 0.10
KYN_SER_ratio_3rd KYN_SER_ratio_3rd 1.03 2.07 1.15 1.79 0.25 0.09
KYN_SER_ratio_BL KYN_SER_ratio_BL 1.11 2.21 1.24 1.78 0.22 0.11
KYN_TRP_ratio_1st KYN_TRP_ratio_1st 1.35 1.56 0.89 1.74 0.37 0.08
KYN_TRP_ratio_3rd KYN_TRP_ratio_3rd 1.43 1.96 1.08 1.81 0.28 0.09
KYN_TRP_ratio_BL KYN_TRP_ratio_BL 1.31 1.99 1.11 1.79 0.27 0.09
KYNA_nM_1st KYNA_nM_1st 1.49 2.14 1.14 1.88 0.26 0.09
KYNA_nM_3rd KYNA_nM_3rd 1.11 2.04 1.10 1.85 0.27 0.09
KYNA_nM_BL KYNA_nM_BL 1.20 1.93 1.04 1.86 0.30 0.09
NIC_nM_1st NIC_nM_1st 1.02 1.40 0.80 1.75 0.42 0.09
NIC_nM_3rd NIC_nM_3rd 1.02 1.87 1.04 1.80 0.30 0.09
NIC_nM_BL NIC_nM_BL 1.02 1.88 1.04 1.80 0.30 0.09
NTA_nM_1st NTA_nM_1st 1.08 1.51 0.87 1.75 0.39 0.08
NTA_nM_3rd NTA_nM_3rd 1.15 2.10 1.15 1.82 0.25 0.09
NTA_nM_BL NTA_nM_BL 1.07 2.17 1.20 1.81 0.23 0.09
PIC_nM_1st PIC_nM_1st 1.06 1.65 0.93 1.77 0.35 0.08
PIC_nM_3rd PIC_nM_3rd 1.09 2.07 1.14 1.82 0.26 0.09
PIC_nM_BL PIC_nM_BL 1.04 2.00 1.12 1.79 0.27 0.09
QUIN_KYNA_ratio_1st QUIN_KYNA_ratio_1st 1.08 1.81 1.05 1.72 0.30 0.12
QUIN_KYNA_ratio_3rd QUIN_KYNA_ratio_3rd 1.04 2.08 1.17 1.79 0.25 0.10
QUIN_KYNA_ratio_BL QUIN_KYNA_ratio_BL 1.13 2.14 1.19 1.81 0.24 0.09
Quin_nM_1st Quin_nM_1st 1.32 1.22 0.67 1.83 0.51 0.09
Quin_nM_3rd Quin_nM_3rd 1.32 1.41 0.74 1.91 0.46 0.10
Quin_nM_BL Quin_nM_BL 1.22 1.37 0.74 1.86 0.46 0.10
QUIN_PIC_ratio_1st QUIN_PIC_ratio_1st 1.08 1.81 1.05 1.72 0.30 0.11
QUIN_PIC_ratio_3rd QUIN_PIC_ratio_3rd 1.15 2.16 1.20 1.80 0.23 0.10
QUIN_PIC_ratio_BL QUIN_PIC_ratio_BL 1.13 2.18 1.22 1.79 0.23 0.10
SAA_ng_mL_1st SAA_ng_mL_1st 1.27 1.44 0.80 1.79 0.42 0.08
SAA_ng_mL_3rd SAA_ng_mL_3rd 1.50 1.78 0.98 1.83 0.33 0.09
SAA_ng_mL_BL SAA_ng_mL_BL 1.27 1.79 0.97 1.83 0.33 0.09
three_HK_nM_1st three_HK_nM_1st 1.09 1.52 0.87 1.75 0.39 0.08
three_HK_nM_3rd three_HK_nM_3rd 1.09 2.13 1.17 1.81 0.24 0.09
three_HK_nM_BL three_HK_nM_BL 1.08 1.99 1.11 1.79 0.27 0.09
threeHK_KYN_ratio_1st threeHK_KYN_ratio_1st 1.05 1.56 0.90 1.73 0.37 0.09
threeHK_KYN_ratio_3rd threeHK_KYN_ratio_3rd 1.02 2.04 1.15 1.78 0.26 0.10
threeHK_KYN_ratio_BL threeHK_KYN_ratio_BL 1.07 2.20 1.22 1.80 0.23 0.10
threeHK_KYNA_ratio_1st threeHK_KYNA_ratio_1st 1.08 1.85 1.05 1.76 0.30 0.10
threeHK_KYNA_ratio_3rd threeHK_KYNA_ratio_3rd 1.07 1.85 1.02 1.81 0.31 0.09
threeHK_KYNA_ratio_BL threeHK_KYNA_ratio_BL 1.14 1.52 0.82 1.85 0.42 0.10
TNFa_pg_mL_1st TNFa_pg_mL_1st 1.15 1.58 0.89 1.76 0.38 0.08
TNFa_pg_mL_3rd TNFa_pg_mL_3rd 1.11 2.00 1.10 1.82 0.27 0.09
TNFa_pg_mL_BL TNFa_pg_mL_BL 1.14 2.09 1.14 1.84 0.26 0.09
TRP_nM_1st TRP_nM_1st 1.10 2.31 1.31 1.77 0.20 0.12
TRP_nM_3rd TRP_nM_3rd 1.27 4.16 2.23 1.86 0.03 0.19
TRP_nM_BL TRP_nM_BL 1.10 3.04 1.70 1.79 0.09 0.15
VCAM_1_ng_mL_1st VCAM_1_ng_mL_1st 1.09 1.66 0.94 1.76 0.35 0.09
VCAM_1_ng_mL_3rd VCAM_1_ng_mL_3rd 1.09 2.11 1.15 1.83 0.25 0.09
VCAM_1_ng_mL_BL VCAM_1_ng_mL_BL 1.10 1.87 1.02 1.83 0.31 0.09

Only TRP_3rd was significant. TRP_BL and KYN_3rd trended to significance.

Visual inspection of biomarker residuals, using models tabulated above

Note: In this html document, multiple QQ plots were excluded for simplicity. I can provide separate file. Also race was left out of the model since there were only 1 asian and 2 blacks

Consolidating transformed variables into final dataframe

Leverage plots (residuals by cooks & hat values)

for (x in final_bx_names) {
  LM1 <- lm(substitute(MADRS_Score_3rd~sex+age+BMI+MADRS_Score_BL+i, list(i=as.name(x))), data=final_df)
  car::influencePlot(LM1, id.method="identify", main=(x), sub= "Influence plot - note: circle size is proportional to Cook’s distance")
}

Univariate analysis by treatment remission

final_df$Remission_new<-ifelse(final_df$MADRS_Score_3rd<9, "Remitter", "Non-Remitter")

createTable(compareGroups(Remission_new ~ ., data = final_df, method = NA), hide.no = '0', show.p.mul    = T)
## 
## --------Summary descriptives table by 'Remission_new'---------
## 
## ___________________________________________________________________________ 
##                              Non-Remitter          Remitter       p.overall 
##                                  N=31                N=41                   
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## AA_nM_3rd_inverse          0.19 [0.16;0.23]    0.21 [0.14;0.26]     0.932   
## AA_nM_BL                   5.25 [4.23;6.44]    5.47 [4.39;7.28]     0.196   
## BSS_Score_BL               8.50 [2.50;13.0]    4.50 [0.75;11.2]     0.147   
## CRP_ng_mL_BL                1675 [433;7521]     931 [503;2197]      0.114   
## CRP_ng_mL_BL_inverse       0.00 [0.00;0.00]    0.00 [0.00;0.00]     0.114   
## five_HT_nM_BL               144 [47.7;415]      69.9 [28.7;190]     0.097   
## ICAM_1_ng_mL_BL              319 [272;398]       282 [254;321]      0.036   
## IFNy_pg_mL_BL              4.95 [4.02;7.46]    5.38 [4.19;7.53]     0.678   
## IL10_pg_mL_BL              0.34 [0.29;0.42]    0.33 [0.26;0.45]     0.618   
## IL10_pg_mL_BL_sqrt         0.59 [0.54;0.65]    0.57 [0.51;0.67]     0.618   
## IL12p70_pg_mL_BL           0.41 [0.34;0.55]    0.35 [0.26;0.46]     0.058   
## IL12p70_pg_mL_LLOD_BL      0.41 [0.34;0.55]    0.35 [0.26;0.46]     0.058   
## IL13_pg_mL_BL              3.48 [3.16;4.02]    3.70 [3.19;4.21]     0.529   
## IL13_pg_mL_LLOD_BL         3.48 [3.16;4.02]    3.66 [3.13;4.20]     0.661   
## IL1B_pg_mL_1st_log           -1.80 (0.87)        -1.82 (1.18)       0.975   
## IL1B_pg_mL_BL              0.10 [0.09;0.18]    0.12 [0.08;0.25]     0.955   
## IL1B_pg_mL_BL_log            -2.18 (1.90)        -2.17 (1.09)       0.996   
## IL1B_pg_mL_LLOD_BL:                                                 0.677   
##     0.323239972               29 (96.7%)          39 (97.5%)                
##     0.412595117                0 (0.00%)           1 (2.50%)                
##     1.605879646                1 (3.33%)           0 (0.00%)                
## IL2_pg_mL_1st_log         -0.94 [-1.40;-0.67] -0.99 [-1.30;-0.70]   0.773   
## IL2_pg_mL_BL               0.49 [0.29;0.57]    0.38 [0.30;0.72]     0.785   
## IL2_pg_mL_LLOD_BL          0.27 [0.10;0.51]    0.26 [0.10;0.50]     0.971   
## IL4_pg_mL_BL               0.09 [0.07;0.10]    0.08 [0.07;0.10]     0.610   
## IL4_pg_mL_LLOD_BL          0.09 [0.07;0.10]    0.08 [0.07;0.10]     0.610   
## IL6_pg_mL_BL               0.93 [0.63;1.37]    0.82 [0.71;1.09]     0.887   
## IL8_pg_mL_BL               3.95 [2.99;4.95]    4.67 [4.07;5.99]     0.040   
## KYN_nM_BL                     1013 (226)           956 (258)        0.327   
## KYN_SER_ratio_1st_inverse  0.11 [0.04;0.42]    0.07 [0.03;0.18]     0.254   
## KYN_SER_ratio_3rd_log         2.14 (1.76)         2.74 (1.47)       0.128   
## KYN_SER_ratio_BL           8.40 [2.15;24.5]    15.3 [4.56;30.3]     0.231   
## KYN_TRP_ratio_BL           0.04 [0.03;0.04]    0.04 [0.03;0.04]     0.924   
## KYNA_nM_BL                 19.6 [14.4;24.0]    19.3 [15.1;24.3]     0.849   
## MADRS_Score_BL                29.0 (5.70)         26.9 (5.69)       0.117   
## NIC_nM_1st_inverse         2.39 [1.59;2.82]    1.52 [0.54;2.68]     0.116   
## NIC_nM_BL                  0.55 [0.31;0.79]    0.53 [0.33;1.14]     0.722   
## NIC_nM_LLOD_BL             0.55 [0.31;0.79]    0.53 [0.33;1.14]     0.722   
## NTA_nM_BL                    300 [215;389]       298 [208;480]      0.731   
## PIC_nM_1st_inverse         0.06 [0.05;0.08]    0.06 [0.04;0.08]     0.880   
## PIC_nM_BL                  17.9 [13.1;23.8]    16.9 [12.2;24.5]     0.722   
## QUIN_KYNA_ratio_BL         7.29 [5.48;8.98]    7.43 [5.76;9.52]     0.868   
## Quin_nM_BL                   142 [109;174]       137 [115;174]      0.962   
## QUIN_PIC_ratio_BL          7.56 [6.15;10.3]    7.62 [5.66;11.6]     0.934   
## SAA_ng_mL_BL               2965 [1789;4670]    1739 [1158;3052]     0.055   
## three_HK_nM_BL             15.4 [13.7;19.2]    14.4 [12.5;19.9]     0.469   
## threeHK_KYN_ratio_BL       0.02 [0.01;0.02]    0.02 [0.01;0.02]     0.427   
## threeHK_KYNA_ratio_BL      0.80 [0.62;1.00]    0.77 [0.64;1.14]     0.962   
## TNFa_pg_mL_BL              1.33 [1.16;1.62]    1.40 [1.23;1.66]     0.740   
## TRP_nM_BL                    28829 (5861)        26846 (5658)       0.160   
## VCAM_1_ng_mL_BL               315 (66.2)          313 (63.3)        0.891   
## sex:                                                                0.951   
##     male                      11 (35.5%)          16 (39.0%)                
##     female                    20 (64.5%)          25 (61.0%)                
## age                        45.0 [28.0;55.0]    49.0 [40.0;55.0]     0.372   
## BMI                           29.1 (6.38)         28.5 (4.99)       0.671   
## MADRS_Score_3rd            15.0 [11.0;20.5]    4.00 [2.00;6.00]    <0.001   
## MADRS_Score_1st               17.6 (7.66)         11.8 (6.18)       0.001   
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

significant variables: IL8_BL, ICAM1_BL, IL12_BL, 5HT_BL

Pearson correlation matrix of biomarkers and psychometrics at baseline

bx_BL_KP<-final_df %>% dplyr::select(all_of(final_bx_names)) %>% select(contains("BL"), -contains("ratio"), -contains("LLOD")) %>% na.omit() %>% stats::cor()

p.mat<-ggcorrplot::cor_pmat(bx_BL_KP)
ggcorrplot::ggcorrplot(bx_BL_KP, 
           hc.order = TRUE, 
           type = "lower", 
           outline.color = "black",
           lab = TRUE,
           lab_size = 3,
           p.mat = p.mat, sig.level=0.05, insig="blank",
           digits=1,
           tl.srt=50,
           tl.cex=10,
           title="Correlation matrix: Bio-K biomarkers & symptoms (baseline, excluding LLOD and ratios)")

Model 1: post-treatment MADRS by baseline TRP, adjusted by demo & interactions

reg_cohend <- function (glm_output) {
  beta <- summary(glm_output)$coefficients[,1]
  SD <- sqrt(dim(glm_output$model)[1])*summary(glm_output)$coefficients[,2]
  cohend <- round(beta/SD,3)
  return(cohend)
}

Model_1<-lm(MADRS_Score_3rd~sex+age+BMI*TRP_nM_BL+MADRS_Score_BL+TRP_nM_BL, data=final_df)
summary(Model_1)
## 
## Call:
## lm(formula = MADRS_Score_3rd ~ sex + age + BMI * TRP_nM_BL + 
##     MADRS_Score_BL + TRP_nM_BL, data = final_df)
## 
## Residuals:
##     Min      1Q  Median      3Q     Max 
## -10.635  -5.406  -0.262   5.061  14.403 
## 
## Coefficients:
##                  Estimate Std. Error t value Pr(>|t|)   
## (Intercept)    -6.384e+01  2.297e+01  -2.780  0.00717 **
## sexfemale       2.286e+00  1.765e+00   1.295  0.20003   
## age             6.981e-02  6.605e-02   1.057  0.29453   
## BMI             1.742e+00  7.456e-01   2.337  0.02263 * 
## TRP_nM_BL       2.125e-03  7.896e-04   2.691  0.00910 **
## MADRS_Score_BL  3.056e-01  1.425e-01   2.144  0.03589 * 
## BMI:TRP_nM_BL  -6.247e-05  2.703e-05  -2.311  0.02412 * 
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 6.621 on 63 degrees of freedom
##   (5 observations deleted due to missingness)
## Multiple R-squared:  0.2182, Adjusted R-squared:  0.1438 
## F-statistic: 2.931 on 6 and 63 DF,  p-value: 0.01382
reg_cohend(Model_1)
##    (Intercept)      sexfemale            age            BMI      TRP_nM_BL MADRS_Score_BL  BMI:TRP_nM_BL 
##         -0.332          0.155          0.126          0.279          0.322          0.256         -0.276
plot(Model_1, which=c(2,5))

Model 2: post-treatment MADRS by baseline 5HT, adjusted by demo & interactions

Model_1<-lm(MADRS_Score_3rd~sex+age*five_HT_nM_BL+BMI+MADRS_Score_BL+five_HT_nM_BL, data=final_df)
summary(Model_1)
## 
## Call:
## lm(formula = MADRS_Score_3rd ~ sex + age * five_HT_nM_BL + BMI + 
##     MADRS_Score_BL + five_HT_nM_BL, data = final_df)
## 
## Residuals:
##    Min     1Q Median     3Q    Max 
## -8.648 -4.521 -1.997  3.678 17.344 
## 
## Coefficients:
##                     Estimate Std. Error t value Pr(>|t|)   
## (Intercept)       -1.227e+01  7.001e+00  -1.752  0.08459 . 
## sexfemale          1.316e+00  1.695e+00   0.777  0.44034   
## age                1.485e-01  8.060e-02   1.843  0.07006 . 
## five_HT_nM_BL      2.184e-02  8.203e-03   2.662  0.00984 **
## BMI                1.072e-01  1.501e-01   0.714  0.47787   
## MADRS_Score_BL     3.359e-01  1.437e-01   2.338  0.02259 * 
## age:five_HT_nM_BL -4.243e-04  2.136e-04  -1.987  0.05133 . 
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 6.654 on 63 degrees of freedom
##   (5 observations deleted due to missingness)
## Multiple R-squared:  0.2103, Adjusted R-squared:  0.1351 
## F-statistic: 2.796 on 6 and 63 DF,  p-value: 0.01782
reg_cohend(Model_1)
##       (Intercept)         sexfemale               age     five_HT_nM_BL               BMI    MADRS_Score_BL age:five_HT_nM_BL 
##            -0.209             0.093             0.220             0.318             0.085             0.279            -0.237
plot(Model_1, which=c(2,5))

Model 3: post-treatment MADRS by baseline IL12, adjusted by demo & interactions

Model_1<-lm(MADRS_Score_3rd~sex+age+BMI*IL12p70_pg_mL_BL+MADRS_Score_BL+IL12p70_pg_mL_BL, data=final_df)
summary(Model_1)
## 
## Call:
## lm(formula = MADRS_Score_3rd ~ sex + age + BMI * IL12p70_pg_mL_BL + 
##     MADRS_Score_BL + IL12p70_pg_mL_BL, data = final_df)
## 
## Residuals:
##    Min     1Q Median     3Q    Max 
## -8.957 -5.119 -1.438  3.786 16.292 
## 
## Coefficients:
##                       Estimate Std. Error t value Pr(>|t|)   
## (Intercept)          -21.41364    8.80718  -2.431  0.01790 * 
## sexfemale              1.91541    1.71538   1.117  0.26840   
## age                    0.06183    0.06777   0.912  0.36512   
## BMI                    0.46758    0.21709   2.154  0.03508 * 
## IL12p70_pg_mL_BL      31.85231   10.77564   2.956  0.00438 **
## MADRS_Score_BL         0.35919    0.14520   2.474  0.01608 * 
## BMI:IL12p70_pg_mL_BL  -0.90483    0.30613  -2.956  0.00438 **
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 6.693 on 63 degrees of freedom
##   (5 observations deleted due to missingness)
## Multiple R-squared:  0.2012, Adjusted R-squared:  0.1251 
## F-statistic: 2.644 on 6 and 63 DF,  p-value: 0.02373
reg_cohend(Model_1)
##          (Intercept)            sexfemale                  age                  BMI     IL12p70_pg_mL_BL       MADRS_Score_BL BMI:IL12p70_pg_mL_BL 
##               -0.291                0.133                0.109                0.257                0.353                0.296               -0.353
plot(Model_1, which=c(2,5))