Correlation between gene methylation status and clinical features
Overview
Introduction

This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.

Summary

Testing the association between 19994 genes and 45 clinical features across 304 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 21 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • C21ORF34 ,  MIR99A ,  MIRLET7C ,  GLDC ,  CHRNB1 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • PMCH ,  MPP7 ,  CLCA3P ,  NUP35 ,  ATP6AP1L ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • ATP10D ,  C10ORF108 ,  DIP2C ,  TMEM117 ,  RGS12 ,  ...

  • 30 genes correlated to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

    • HIST1H1E ,  CLEC2L ,  C22ORF30 ,  RSPH3 ,  AGPAT3 ,  ...

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • RCAN1 ,  NUAK1 ,  BCL9 ,  PPARGC1A ,  RNF20 ,  ...

  • 30 genes correlated to 'RACE'.

    • SNX16 ,  IFNGR2 ,  PDXDC1 ,  RNF151 ,  RPS2__3 ,  ...

  • 30 genes correlated to 'TUMOR_SAMPLE_PROCUREMENT_COUNTRY'.

    • C8ORF77 ,  ZNF252 ,  GPRIN1 ,  HAX1 ,  C3ORF47 ,  ...

  • 30 genes correlated to 'NEOPLASM_HISTOLOGIC_GRADE'.

    • GMNN ,  MTF2 ,  MRPS9 ,  BRIX1__1 ,  RAD1__1 ,  ...

  • 30 genes correlated to 'RADIATION_TOTAL_DOSE'.

    • HNRNPH3 ,  PBLD ,  HIST2H2AB ,  GNRHR2__1 ,  PEX11B__1 ,  ...

  • 30 genes correlated to 'RADIATION_THERAPY_TYPE'.

    • CLEC2L ,  HIST1H1E ,  RSPH3 ,  PRPF6 ,  C22ORF30 ,  ...

  • 6 genes correlated to 'RADIATION_THERAPY_SITE'.

    • PRH1__8 ,  PRR4__8 ,  TAS2R20 ,  MYL6B ,  MAPK6 ,  ...

  • 30 genes correlated to 'PATIENT_PATIENTPREGNANCYSPONTANEOUSABORTIONCOUNT'.

    • GPRIN1 ,  TAF3 ,  POLR2D ,  ZBTB1 ,  ZBTB25 ,  ...

  • 30 genes correlated to 'PREGNANCIES_COUNT_LIVE_BIRTH'.

    • POLE ,  PXMP2 ,  PALM3 ,  ZNF488 ,  PGF ,  ...

  • 30 genes correlated to 'MENOPAUSE_STATUS'.

    • C21ORF34 ,  MIR99A ,  MIRLET7C ,  RARB ,  FBXW11 ,  ...

  • 30 genes correlated to 'LYMPHOVASCULAR_INVOLVEMENT'.

    • MKRN2 ,  HYAL3__1 ,  NAT6__1 ,  ZNF197 ,  TMED7 ,  ...

  • 30 genes correlated to 'LYMPH_NODES_EXAMINED_HE_COUNT'.

    • RCAN1 ,  NUAK1 ,  BCL9 ,  PPARGC1A ,  RNF20 ,  ...

  • 24 genes correlated to 'LYMPH_NODES_EXAMINED'.

    • LOC643837 ,  GAR1 ,  HDAC1 ,  NIPA1 ,  TTLL10 ,  ...

  • 30 genes correlated to 'INITIAL_PATHOLOGIC_DX_YEAR'.

    • KLHL9 ,  RHOT2 ,  MMD ,  DCDC1 ,  DNAJC24 ,  ...

  • 30 genes correlated to 'AJCC_TUMOR_PATHOLOGIC_PT'.

    • CATSPERB ,  AP4E1__1 ,  LOC100132724 ,  C8ORF77 ,  ZNF252 ,  ...

  • 30 genes correlated to 'AGE_AT_DIAGNOSIS'.

    • C21ORF34 ,  MIR99A ,  MIRLET7C ,  GLDC ,  MDFI ,  ...

  • 30 genes correlated to 'STAGE_EVENT.CLINICAL_STAGE'.

    • ARF4 ,  DPY30 ,  TMEM50A ,  C3ORF48 ,  RAB5A ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'PATHOLOGY_N_STAGE', 'PATHOLOGY_M_STAGE', 'NUMBER_PACK_YEARS_SMOKED', 'ETHNICITY', 'WEIGHT_KG_AT_DIAGNOSIS', 'TUMOR_STATUS', 'TOBACCO_SMOKING_YEAR_STOPPED', 'TOBACCO_SMOKING_PACK_YEARS_SMOKED', 'TOBACCO_SMOKING_HISTORY', 'PATIENT.AGEBEGANSMOKINGINYEARS', 'RADIATION_THERAPY_STATUS', 'RADIATION_ADJUVANT_UNITS', 'PREGNANCIES_COUNT_TOTAL', 'PREGNANCIES_COUNT_STILLBIRTH', 'PATIENT_PATIENTPREGNANCYTHERAPEUTICABORTIONCOUNT', 'PREGNANCIES_COUNT_ECTOPIC', 'POS_LYMPH_NODE_LOCATION', 'KERATINIZATION_SQUAMOUS_CELL', 'HISTORY_HORMONAL_CONTRACEPTIVES_USE', 'HEIGHT_CM_AT_DIAGNOSIS', 'CORPUS_INVOLVEMENT', 'CHEMO_CONCURRENT_TYPE', and 'CERVIX_SUV_RESULTS'.

Results
Overview of the results

Complete statistical result table is provided in Supplement Table 1

Table 1.  Get Full Table This table shows the clinical features, statistical methods used, and the number of genes that are significantly associated with each clinical feature at P value < 0.05 and Q value < 0.3.

Clinical feature Statistical test Significant genes Associated with                 Associated with
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test   N=0        
YEARS_TO_BIRTH Spearman correlation test N=30 older N=11 younger N=19
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=3 lower stage N=27
PATHOLOGY_N_STAGE Wilcoxon test   N=0        
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test N=30 yes N=30 no N=0
NUMBER_PACK_YEARS_SMOKED Spearman correlation test   N=0        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=30 higher number_of_lymph_nodes N=24 lower number_of_lymph_nodes N=6
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test   N=0        
WEIGHT_KG_AT_DIAGNOSIS Spearman correlation test   N=0        
TUMOR_STATUS Wilcoxon test   N=0        
TUMOR_SAMPLE_PROCUREMENT_COUNTRY Kruskal-Wallis test N=30        
NEOPLASM_HISTOLOGIC_GRADE Kruskal-Wallis test N=30        
TOBACCO_SMOKING_YEAR_STOPPED Spearman correlation test   N=0        
TOBACCO_SMOKING_PACK_YEARS_SMOKED Spearman correlation test   N=0        
TOBACCO_SMOKING_HISTORY Kruskal-Wallis test   N=0        
PATIENT AGEBEGANSMOKINGINYEARS Spearman correlation test   N=0        
RADIATION_TOTAL_DOSE Spearman correlation test N=30 higher radiation_total_dose N=25 lower radiation_total_dose N=5
RADIATION_THERAPY_TYPE Kruskal-Wallis test N=30        
RADIATION_THERAPY_STATUS Wilcoxon test   N=0        
RADIATION_THERAPY_SITE Kruskal-Wallis test N=6        
RADIATION_ADJUVANT_UNITS Wilcoxon test   N=0        
PREGNANCIES_COUNT_TOTAL Spearman correlation test   N=0        
PREGNANCIES_COUNT_STILLBIRTH Spearman correlation test   N=0        
PATIENT_PATIENTPREGNANCYSPONTANEOUSABORTIONCOUNT Spearman correlation test N=30 higher patient_patientpregnancyspontaneousabortioncount N=14 lower patient_patientpregnancyspontaneousabortioncount N=16
PREGNANCIES_COUNT_LIVE_BIRTH Spearman correlation test N=30 higher pregnancies_count_live_birth N=13 lower pregnancies_count_live_birth N=17
PATIENT_PATIENTPREGNANCYTHERAPEUTICABORTIONCOUNT Spearman correlation test   N=0        
PREGNANCIES_COUNT_ECTOPIC Spearman correlation test   N=0        
POS_LYMPH_NODE_LOCATION Kruskal-Wallis test   N=0        
MENOPAUSE_STATUS Kruskal-Wallis test N=30        
LYMPHOVASCULAR_INVOLVEMENT Wilcoxon test N=30 present N=30 absent N=0
LYMPH_NODES_EXAMINED_HE_COUNT Spearman correlation test N=30 higher lymph_nodes_examined_he_count N=24 lower lymph_nodes_examined_he_count N=6
LYMPH_NODES_EXAMINED Spearman correlation test N=24 higher lymph_nodes_examined N=24 lower lymph_nodes_examined N=0
KERATINIZATION_SQUAMOUS_CELL Wilcoxon test   N=0        
INITIAL_PATHOLOGIC_DX_YEAR Spearman correlation test N=30 higher initial_pathologic_dx_year N=2 lower initial_pathologic_dx_year N=28
HISTORY_HORMONAL_CONTRACEPTIVES_USE Kruskal-Wallis test   N=0        
HEIGHT_CM_AT_DIAGNOSIS Spearman correlation test   N=0        
CORPUS_INVOLVEMENT Wilcoxon test   N=0        
CHEMO_CONCURRENT_TYPE Kruskal-Wallis test   N=0        
CERVIX_SUV_RESULTS Spearman correlation test   N=0        
AJCC_TUMOR_PATHOLOGIC_PT Kruskal-Wallis test N=30        
AGE_AT_DIAGNOSIS Spearman correlation test N=30 higher age_at_diagnosis N=12 lower age_at_diagnosis N=18
STAGE_EVENT CLINICAL_STAGE Kruskal-Wallis test N=30        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

No gene related to 'DAYS_TO_DEATH_OR_LAST_FUP'.

Table S1.  Basic characteristics of clinical feature: 'DAYS_TO_DEATH_OR_LAST_FUP'

DAYS_TO_DEATH_OR_LAST_FUP Duration (Months) 0-210.7 (median=20.1)
  censored N = 234
  death N = 69
     
  Significant markers N = 0
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

Table S2.  Basic characteristics of clinical feature: 'YEARS_TO_BIRTH'

YEARS_TO_BIRTH Mean (SD) 48.11 (14)
  Significant markers N = 30
  pos. correlated 11
  neg. correlated 19
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S3.  Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
C21ORF34 -0.3153 2.375e-08 0.000158
MIR99A -0.3153 2.375e-08 0.000158
MIRLET7C -0.3153 2.375e-08 0.000158
GLDC 0.3116 3.534e-08 0.000169
CHRNB1 0.3094 4.454e-08 0.000169
SP4 -0.3082 5.077e-08 0.000169
MDFI 0.3054 6.791e-08 0.000194
RARB -0.3037 8.039e-08 0.000201
C10ORF67 0.2962 1.726e-07 0.000371
CCDC23 -0.2938 2.195e-07 0.000371
Clinical variable #3: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S4.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 1.59 (0.82)
  N
  T1 140
  T2 70
  T3 21
  T4 10
     
  Significant markers N = 30
  pos. correlated 3
  neg. correlated 27
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S5.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
PMCH -0.3497 2.432e-08 0.000182
MPP7 -0.349 2.609e-08 0.000182
CLCA3P -0.3486 2.723e-08 0.000182
NUP35 0.3425 4.9e-08 0.000191
ATP6AP1L -0.3381 7.391e-08 0.000191
DKFZP586I1420 -0.3384 7.701e-08 0.000191
TANC2 -0.3365 8.651e-08 0.000191
TMEM86B -0.336 8.991e-08 0.000191
MIR155 -0.3345 1.037e-07 0.000191
MIR155HG -0.3345 1.037e-07 0.000191
Clinical variable #4: 'PATHOLOGY_N_STAGE'

No gene related to 'PATHOLOGY_N_STAGE'.

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Labels N
  N0 133
  N1 59
     
  Significant markers N = 0
Clinical variable #5: 'PATHOLOGY_M_STAGE'

No gene related to 'PATHOLOGY_M_STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY_M_STAGE'

PATHOLOGY_M_STAGE Labels N
  class0 115
  class1 10
     
  Significant markers N = 0
Clinical variable #6: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

Table S8.  Basic characteristics of clinical feature: 'HISTOLOGICAL_TYPE'

HISTOLOGICAL_TYPE Labels N
  ADENOSQUAMOUS 5
  CERVICAL SQUAMOUS CELL CARCINOMA 253
  ENDOCERVICAL ADENOCARCINOMA OF THE USUAL TYPE 6
  ENDOCERVICAL TYPE OF ADENOCARCINOMA 22
  ENDOMETRIOID ADENOCARCINOMA OF ENDOCERVIX 3
  MUCINOUS ADENOCARCINOMA OF ENDOCERVICAL TYPE 15
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S9.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
ATP10D 1.175e-21 2.35e-17
C10ORF108 1.609e-20 8.28e-17
DIP2C 1.609e-20 8.28e-17
TMEM117 1.657e-20 8.28e-17
RGS12 2.718e-20 1.01e-16
CLDN3 3.032e-20 1.01e-16
HR 4.697e-20 1.27e-16
GPR87 5.7e-20 1.27e-16
MED12L__5 5.7e-20 1.27e-16
BICD2 1.063e-19 2.13e-16
Clinical variable #7: 'RADIATIONS_RADIATION_REGIMENINDICATION'

30 genes related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

Table S10.  Basic characteristics of clinical feature: 'RADIATIONS_RADIATION_REGIMENINDICATION'

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 35
  YES 269
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS_RADIATION_REGIMENINDICATION'

W(pos if higher in 'YES') wilcoxontestP Q AUC
HIST1H1E 8130 2.646e-12 3.92e-08 0.8635
CLEC2L 1312 3.916e-12 3.92e-08 0.8606
C22ORF30 1418 1.774e-11 1.18e-07 0.8494
RSPH3 1467 3.512e-11 1.51e-07 0.8442
AGPAT3 1472 3.764e-11 1.51e-07 0.8437
UNC13B 1519 7.172e-11 2.39e-07 0.8387
PRPF6 1586 1.77e-10 4.56e-07 0.8315
PLEKHA8 1592 1.918e-10 4.56e-07 0.8309
BTBD7__1 1605 2.28e-10 4.56e-07 0.8295
KIAA1409 1605 2.28e-10 4.56e-07 0.8295
Clinical variable #8: 'NUMBER_PACK_YEARS_SMOKED'

No gene related to 'NUMBER_PACK_YEARS_SMOKED'.

Table S12.  Basic characteristics of clinical feature: 'NUMBER_PACK_YEARS_SMOKED'

NUMBER_PACK_YEARS_SMOKED Mean (SD) 17.38 (14)
  Significant markers N = 0
Clinical variable #9: 'NUMBER_OF_LYMPH_NODES'

30 genes related to 'NUMBER_OF_LYMPH_NODES'.

Table S13.  Basic characteristics of clinical feature: 'NUMBER_OF_LYMPH_NODES'

NUMBER_OF_LYMPH_NODES Mean (SD) 1.05 (2.4)
  Significant markers N = 30
  pos. correlated 24
  neg. correlated 6
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S14.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
RCAN1 0.4083 1.108e-07 0.00222
NUAK1 0.3711 1.708e-06 0.0171
BCL9 0.3563 4.655e-06 0.031
PPARGC1A 0.3284 2.677e-05 0.0888
RNF20 -0.327 2.918e-05 0.0888
ARIH2__1 0.3255 3.181e-05 0.0888
C3ORF71__1 0.3255 3.181e-05 0.0888
GAL3ST3 -0.3201 4.383e-05 0.0888
TXNDC6 0.3188 4.72e-05 0.0888
DRAM1 0.3159 5.557e-05 0.0888
Clinical variable #10: 'RACE'

30 genes related to 'RACE'.

Table S15.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 8
  ASIAN 19
  BLACK OR AFRICAN AMERICAN 30
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 2
  WHITE 210
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S16.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
SNX16 1.344e-06 0.0269
IFNGR2 4.161e-06 0.0302
PDXDC1 8.336e-06 0.0302
RNF151 9.056e-06 0.0302
RPS2__3 9.056e-06 0.0302
SNHG9__2 9.056e-06 0.0302
HSD17B4 1.166e-05 0.0333
TLE1 1.827e-05 0.0457
NDUFS5 2.678e-05 0.0595
GPBAR1 3.178e-05 0.0631
Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S17.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 24
  NOT HISPANIC OR LATINO 169
     
  Significant markers N = 0
Clinical variable #12: 'WEIGHT_KG_AT_DIAGNOSIS'

No gene related to 'WEIGHT_KG_AT_DIAGNOSIS'.

Table S18.  Basic characteristics of clinical feature: 'WEIGHT_KG_AT_DIAGNOSIS'

WEIGHT_KG_AT_DIAGNOSIS Mean (SD) 73.26 (21)
  Significant markers N = 0
Clinical variable #13: 'TUMOR_STATUS'

No gene related to 'TUMOR_STATUS'.

Table S19.  Basic characteristics of clinical feature: 'TUMOR_STATUS'

TUMOR_STATUS Labels N
  TUMOR FREE 139
  WITH TUMOR 44
     
  Significant markers N = 0
Clinical variable #14: 'TUMOR_SAMPLE_PROCUREMENT_COUNTRY'

30 genes related to 'TUMOR_SAMPLE_PROCUREMENT_COUNTRY'.

Table S20.  Basic characteristics of clinical feature: 'TUMOR_SAMPLE_PROCUREMENT_COUNTRY'

TUMOR_SAMPLE_PROCUREMENT_COUNTRY Labels N
  BRAZIL 54
  CANADA 5
  NIGERIA 1
  RUSSIA 12
  UKRAINE 7
  UNITED STATES 211
  VIETNAM 14
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'TUMOR_SAMPLE_PROCUREMENT_COUNTRY'

Table S21.  Get Full Table List of top 10 genes differentially expressed by 'TUMOR_SAMPLE_PROCUREMENT_COUNTRY'

kruskal_wallis_P Q
C8ORF77 1.27e-16 1.27e-12
ZNF252 1.27e-16 1.27e-12
GPRIN1 1.072e-15 7.15e-12
HAX1 1.941e-15 9.7e-12
C3ORF47 3.667e-15 1.22e-11
H1FX 3.667e-15 1.22e-11
KIAA0100 1.818e-14 4.82e-11
CTSA__1 2.17e-14 4.82e-11
NEURL2__1 2.17e-14 4.82e-11
C20ORF11 5.357e-14 9.74e-11
Clinical variable #15: 'NEOPLASM_HISTOLOGIC_GRADE'

30 genes related to 'NEOPLASM_HISTOLOGIC_GRADE'.

Table S22.  Basic characteristics of clinical feature: 'NEOPLASM_HISTOLOGIC_GRADE'

NEOPLASM_HISTOLOGIC_GRADE Labels N
  G1 18
  G2 136
  G3 118
  G4 1
  GX 24
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'NEOPLASM_HISTOLOGIC_GRADE'

Table S23.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM_HISTOLOGIC_GRADE'

kruskal_wallis_P Q
GMNN 2.534e-08 0.000452
MTF2 4.519e-08 0.000452
MRPS9 3.784e-07 0.00176
BRIX1__1 4.406e-07 0.00176
RAD1__1 4.406e-07 0.00176
PASK 7.384e-07 0.00211
PPP1R7 7.384e-07 0.00211
MYL6 9.43e-07 0.00236
PAIP1 1.185e-06 0.00263
C9ORF40 1.526e-06 0.00305
Clinical variable #16: 'TOBACCO_SMOKING_YEAR_STOPPED'

No gene related to 'TOBACCO_SMOKING_YEAR_STOPPED'.

Table S24.  Basic characteristics of clinical feature: 'TOBACCO_SMOKING_YEAR_STOPPED'

TOBACCO_SMOKING_YEAR_STOPPED Mean (SD) 1999.69 (14)
  Significant markers N = 0
Clinical variable #17: 'TOBACCO_SMOKING_PACK_YEARS_SMOKED'

No gene related to 'TOBACCO_SMOKING_PACK_YEARS_SMOKED'.

Table S25.  Basic characteristics of clinical feature: 'TOBACCO_SMOKING_PACK_YEARS_SMOKED'

TOBACCO_SMOKING_PACK_YEARS_SMOKED Mean (SD) 17.38 (14)
  Significant markers N = 0
Clinical variable #18: 'TOBACCO_SMOKING_HISTORY'

No gene related to 'TOBACCO_SMOKING_HISTORY'.

Table S26.  Basic characteristics of clinical feature: 'TOBACCO_SMOKING_HISTORY'

TOBACCO_SMOKING_HISTORY Labels N
  CURRENT REFORMED SMOKER FOR < OR = 15 YEARS 39
  CURRENT REFORMED SMOKER FOR > 15 YEARS 9
  CURRENT REFORMED SMOKER, DURATION NOT SPECIFIED 4
  CURRENT SMOKER 64
  LIFELONG NON-SMOKER 145
     
  Significant markers N = 0
Clinical variable #19: 'PATIENT.AGEBEGANSMOKINGINYEARS'

No gene related to 'PATIENT.AGEBEGANSMOKINGINYEARS'.

Table S27.  Basic characteristics of clinical feature: 'PATIENT.AGEBEGANSMOKINGINYEARS'

PATIENT.AGEBEGANSMOKINGINYEARS Mean (SD) 21.14 (7.7)
  Significant markers N = 0
Clinical variable #20: 'RADIATION_TOTAL_DOSE'

30 genes related to 'RADIATION_TOTAL_DOSE'.

Table S28.  Basic characteristics of clinical feature: 'RADIATION_TOTAL_DOSE'

RADIATION_TOTAL_DOSE Mean (SD) 3635.38 (1700)
  Significant markers N = 30
  pos. correlated 25
  neg. correlated 5
List of top 10 genes differentially expressed by 'RADIATION_TOTAL_DOSE'

Table S29.  Get Full Table List of top 10 genes significantly correlated to 'RADIATION_TOTAL_DOSE' by Spearman correlation test

SpearmanCorr corrP Q
HNRNPH3 0.3548 9.031e-06 0.0396
PBLD 0.3548 9.031e-06 0.0396
HIST2H2AB 0.3491 1.281e-05 0.0396
GNRHR2__1 0.3488 1.304e-05 0.0396
PEX11B__1 0.3488 1.304e-05 0.0396
MTHFS 0.3482 1.354e-05 0.0396
SPINK6 0.3478 1.386e-05 0.0396
COL10A1 0.3361 2.78e-05 0.0618
NT5DC1 0.3361 2.78e-05 0.0618
RHOT2 0.3318 3.563e-05 0.0664
Clinical variable #21: 'RADIATION_THERAPY_TYPE'

30 genes related to 'RADIATION_THERAPY_TYPE'.

Table S30.  Basic characteristics of clinical feature: 'RADIATION_THERAPY_TYPE'

RADIATION_THERAPY_TYPE Labels N
  COMBINATION 20
  EXTERNAL 104
  EXTERNAL BEAM 15
  IMPLANTS 1
  INTERNAL 25
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RADIATION_THERAPY_TYPE'

Table S31.  Get Full Table List of top 10 genes differentially expressed by 'RADIATION_THERAPY_TYPE'

kruskal_wallis_P Q
CLEC2L 1.425e-12 2.85e-08
HIST1H1E 2.895e-12 2.89e-08
RSPH3 5.512e-12 3.67e-08
PRPF6 1.344e-11 6.72e-08
C22ORF30 2.177e-11 8.71e-08
ATP6V1F 5.307e-11 1.77e-07
BTBD7__1 7.705e-11 1.93e-07
KIAA1409 7.705e-11 1.93e-07
LOC729156 2.039e-10 4.53e-07
KLHL9 3.9e-10 7.8e-07
Clinical variable #22: 'RADIATION_THERAPY_STATUS'

No gene related to 'RADIATION_THERAPY_STATUS'.

Table S32.  Basic characteristics of clinical feature: 'RADIATION_THERAPY_STATUS'

RADIATION_THERAPY_STATUS Labels N
  COMPLETED AS PLANNED 29
  TREATMENT NOT COMPLETED 3
     
  Significant markers N = 0
Clinical variable #23: 'RADIATION_THERAPY_SITE'

6 genes related to 'RADIATION_THERAPY_SITE'.

Table S33.  Basic characteristics of clinical feature: 'RADIATION_THERAPY_SITE'

RADIATION_THERAPY_SITE Labels N
  DISTANT RECURRENCE 2
  LOCAL RECURRENCE 2
  PRIMARY TUMOR FIELD 38
  REGIONAL SITE 33
     
  Significant markers N = 6
List of 6 genes differentially expressed by 'RADIATION_THERAPY_SITE'

Table S34.  Get Full Table List of 6 genes differentially expressed by 'RADIATION_THERAPY_SITE'

kruskal_wallis_P Q
PRH1__8 2.2e-05 0.147
PRR4__8 2.2e-05 0.147
TAS2R20 2.2e-05 0.147
MYL6B 4.059e-05 0.203
MAPK6 8.265e-05 0.298
DLG1 8.957e-05 0.298
Clinical variable #24: 'RADIATION_ADJUVANT_UNITS'

No gene related to 'RADIATION_ADJUVANT_UNITS'.

Table S35.  Basic characteristics of clinical feature: 'RADIATION_ADJUVANT_UNITS'

RADIATION_ADJUVANT_UNITS Labels N
  CGY 58
  GY 5
     
  Significant markers N = 0
Clinical variable #25: 'PREGNANCIES_COUNT_TOTAL'

No gene related to 'PREGNANCIES_COUNT_TOTAL'.

Table S36.  Basic characteristics of clinical feature: 'PREGNANCIES_COUNT_TOTAL'

PREGNANCIES_COUNT_TOTAL Mean (SD) 3.62 (2.6)
  Significant markers N = 0
Clinical variable #26: 'PREGNANCIES_COUNT_STILLBIRTH'

No gene related to 'PREGNANCIES_COUNT_STILLBIRTH'.

Table S37.  Basic characteristics of clinical feature: 'PREGNANCIES_COUNT_STILLBIRTH'

PREGNANCIES_COUNT_STILLBIRTH Mean (SD) 0.07 (0.35)
  Value N
  0 105
  1 5
  3 1
     
  Significant markers N = 0
Clinical variable #27: 'PATIENT_PATIENTPREGNANCYSPONTANEOUSABORTIONCOUNT'

30 genes related to 'PATIENT_PATIENTPREGNANCYSPONTANEOUSABORTIONCOUNT'.

Table S38.  Basic characteristics of clinical feature: 'PATIENT_PATIENTPREGNANCYSPONTANEOUSABORTIONCOUNT'

PATIENT_PATIENTPREGNANCYSPONTANEOUSABORTIONCOUNT Mean (SD) 0.55 (0.95)
  Significant markers N = 30
  pos. correlated 14
  neg. correlated 16
List of top 10 genes differentially expressed by 'PATIENT_PATIENTPREGNANCYSPONTANEOUSABORTIONCOUNT'

Table S39.  Get Full Table List of top 10 genes significantly correlated to 'PATIENT_PATIENTPREGNANCYSPONTANEOUSABORTIONCOUNT' by Spearman correlation test

SpearmanCorr corrP Q
GPRIN1 -0.457 6.691e-09 0.000134
TAF3 0.4457 1.728e-08 0.000173
POLR2D 0.4365 3.65e-08 0.000243
ZBTB1 -0.4147 1.955e-07 0.00057
ZBTB25 -0.4147 1.955e-07 0.00057
C8ORF77 -0.4127 2.262e-07 0.00057
ZNF252 -0.4127 2.262e-07 0.00057
ZNF592 -0.4126 2.281e-07 0.00057
TRIM56 -0.406 3.696e-07 0.000764
ATL3 -0.4045 4.126e-07 0.000764
Clinical variable #28: 'PREGNANCIES_COUNT_LIVE_BIRTH'

30 genes related to 'PREGNANCIES_COUNT_LIVE_BIRTH'.

Table S40.  Basic characteristics of clinical feature: 'PREGNANCIES_COUNT_LIVE_BIRTH'

PREGNANCIES_COUNT_LIVE_BIRTH Mean (SD) 2.85 (2.1)
  Significant markers N = 30
  pos. correlated 13
  neg. correlated 17
List of top 10 genes differentially expressed by 'PREGNANCIES_COUNT_LIVE_BIRTH'

Table S41.  Get Full Table List of top 10 genes significantly correlated to 'PREGNANCIES_COUNT_LIVE_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
POLE -0.3362 2.724e-08 0.000272
PXMP2 -0.3362 2.724e-08 0.000272
PALM3 -0.3202 1.382e-07 0.000921
ZNF488 -0.3154 2.064e-07 0.00103
PGF -0.3026 6.57e-07 0.00263
ZNF713 -0.3038 1.087e-06 0.00362
PDP2 -0.2952 1.268e-06 0.00362
LHX4 -0.2927 1.569e-06 0.00362
GPRIN1 -0.2922 1.632e-06 0.00362
LOC100144604 -0.2807 4.285e-06 0.00729
Clinical variable #29: 'PATIENT_PATIENTPREGNANCYTHERAPEUTICABORTIONCOUNT'

No gene related to 'PATIENT_PATIENTPREGNANCYTHERAPEUTICABORTIONCOUNT'.

Table S42.  Basic characteristics of clinical feature: 'PATIENT_PATIENTPREGNANCYTHERAPEUTICABORTIONCOUNT'

PATIENT_PATIENTPREGNANCYTHERAPEUTICABORTIONCOUNT Mean (SD) 0.86 (1.8)
  Significant markers N = 0
Clinical variable #30: 'PREGNANCIES_COUNT_ECTOPIC'

No gene related to 'PREGNANCIES_COUNT_ECTOPIC'.

Table S43.  Basic characteristics of clinical feature: 'PREGNANCIES_COUNT_ECTOPIC'

PREGNANCIES_COUNT_ECTOPIC Mean (SD) 0.11 (0.34)
  Value N
  0 103
  1 11
  2 1
     
  Significant markers N = 0
Clinical variable #31: 'POS_LYMPH_NODE_LOCATION'

No gene related to 'POS_LYMPH_NODE_LOCATION'.

Table S44.  Basic characteristics of clinical feature: 'POS_LYMPH_NODE_LOCATION'

POS_LYMPH_NODE_LOCATION Labels N
  MACROSCOPIC PARAMETRIAL INVOLVEMENT 2
  MICROSCOPIC PARAMETRIAL INVOLVEMENT 8
  OTHER LOCATION, SPECIFY 39
  POSITIVE BLADDER MARGIN 1
  POSITIVE VAGINAL MARGIN 10
     
  Significant markers N = 0
Clinical variable #32: 'MENOPAUSE_STATUS'

30 genes related to 'MENOPAUSE_STATUS'.

Table S45.  Basic characteristics of clinical feature: 'MENOPAUSE_STATUS'

MENOPAUSE_STATUS Labels N
  INDETERMINATE (NEITHER PRE OR POSTMENOPAUSAL) 2
  PERI (6-12 MONTHS SINCE LAST MENSTRUAL PERIOD) 25
  POST (PRIOR BILATERAL OVARIECTOMY OR >12 MO SINCE LMP WITH NO PRIOR HYSTERECTOMY) 83
  PRE (<6 MONTHS SINCE LMP AND NO PRIOR BILATERAL OVARIECTOMY AND NOT ON ESTROGEN REPLACEMENT) 124
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'MENOPAUSE_STATUS'

Table S46.  Get Full Table List of top 10 genes differentially expressed by 'MENOPAUSE_STATUS'

kruskal_wallis_P Q
C21ORF34 1.566e-06 0.0104
MIR99A 1.566e-06 0.0104
MIRLET7C 1.566e-06 0.0104
RARB 3.597e-06 0.018
FBXW11 7.593e-06 0.0304
CMTM7 1.586e-05 0.0528
KCNC4 2.018e-05 0.0576
SMARCB1 2.729e-05 0.0678
CD9 3.64e-05 0.0678
F3 3.699e-05 0.0678
Clinical variable #33: 'LYMPHOVASCULAR_INVOLVEMENT'

30 genes related to 'LYMPHOVASCULAR_INVOLVEMENT'.

Table S47.  Basic characteristics of clinical feature: 'LYMPHOVASCULAR_INVOLVEMENT'

LYMPHOVASCULAR_INVOLVEMENT Labels N
  ABSENT 71
  PRESENT 79
     
  Significant markers N = 30
  Higher in PRESENT 30
  Higher in ABSENT 0
List of top 10 genes differentially expressed by 'LYMPHOVASCULAR_INVOLVEMENT'

Clinical variable #34: 'LYMPH_NODES_EXAMINED_HE_COUNT'

30 genes related to 'LYMPH_NODES_EXAMINED_HE_COUNT'.

Table S49.  Basic characteristics of clinical feature: 'LYMPH_NODES_EXAMINED_HE_COUNT'

LYMPH_NODES_EXAMINED_HE_COUNT Mean (SD) 1.05 (2.4)
  Significant markers N = 30
  pos. correlated 24
  neg. correlated 6
List of top 10 genes differentially expressed by 'LYMPH_NODES_EXAMINED_HE_COUNT'

Table S50.  Get Full Table List of top 10 genes significantly correlated to 'LYMPH_NODES_EXAMINED_HE_COUNT' by Spearman correlation test

SpearmanCorr corrP Q
RCAN1 0.4083 1.108e-07 0.00222
NUAK1 0.3711 1.708e-06 0.0171
BCL9 0.3563 4.655e-06 0.031
PPARGC1A 0.3284 2.677e-05 0.0888
RNF20 -0.327 2.918e-05 0.0888
ARIH2__1 0.3255 3.181e-05 0.0888
C3ORF71__1 0.3255 3.181e-05 0.0888
GAL3ST3 -0.3201 4.383e-05 0.0888
TXNDC6 0.3188 4.72e-05 0.0888
DRAM1 0.3159 5.557e-05 0.0888
Clinical variable #35: 'LYMPH_NODES_EXAMINED'

24 genes related to 'LYMPH_NODES_EXAMINED'.

Table S51.  Basic characteristics of clinical feature: 'LYMPH_NODES_EXAMINED'

LYMPH_NODES_EXAMINED Mean (SD) 22.35 (13)
  Significant markers N = 24
  pos. correlated 24
  neg. correlated 0
List of top 10 genes differentially expressed by 'LYMPH_NODES_EXAMINED'

Table S52.  Get Full Table List of top 10 genes significantly correlated to 'LYMPH_NODES_EXAMINED' by Spearman correlation test

SpearmanCorr corrP Q
LOC643837 0.3119 2.253e-05 0.284
GAR1 0.2966 6.096e-05 0.284
HDAC1 0.2951 6.384e-05 0.284
NIPA1 0.2938 6.867e-05 0.284
TTLL10 0.2853 0.0001133 0.284
DPH5 0.2852 0.0001138 0.284
CCDC134 0.2835 0.0001259 0.284
MPP2 0.2838 0.0001295 0.284
ULK1 0.2829 0.00013 0.284
HM13 0.2806 0.0001482 0.284
Clinical variable #36: 'KERATINIZATION_SQUAMOUS_CELL'

No gene related to 'KERATINIZATION_SQUAMOUS_CELL'.

Table S53.  Basic characteristics of clinical feature: 'KERATINIZATION_SQUAMOUS_CELL'

KERATINIZATION_SQUAMOUS_CELL Labels N
  KERATINIZING SQUAMOUS CELL CARCINOMA 54
  NON-KERATINIZING SQUAMOUS CELL CARCINOMA 119
     
  Significant markers N = 0
Clinical variable #37: 'INITIAL_PATHOLOGIC_DX_YEAR'

30 genes related to 'INITIAL_PATHOLOGIC_DX_YEAR'.

Table S54.  Basic characteristics of clinical feature: 'INITIAL_PATHOLOGIC_DX_YEAR'

INITIAL_PATHOLOGIC_DX_YEAR Mean (SD) 2008.29 (4.8)
  Significant markers N = 30
  pos. correlated 2
  neg. correlated 28
List of top 10 genes differentially expressed by 'INITIAL_PATHOLOGIC_DX_YEAR'

Table S55.  Get Full Table List of top 10 genes significantly correlated to 'INITIAL_PATHOLOGIC_DX_YEAR' by Spearman correlation test

SpearmanCorr corrP Q
KLHL9 0.3673 4.438e-11 8.24e-07
RHOT2 -0.3597 1.176e-10 8.24e-07
MMD -0.3555 2.004e-10 8.24e-07
DCDC1 -0.3548 2.172e-10 8.24e-07
DNAJC24 -0.3548 2.172e-10 8.24e-07
HIST1H1E 0.3538 2.474e-10 8.24e-07
LOC285456 -0.3461 6.338e-10 1.42e-06
RPL34 -0.3461 6.338e-10 1.42e-06
MYLPF -0.3461 6.378e-10 1.42e-06
C9ORF44 -0.3448 7.395e-10 1.48e-06
Clinical variable #38: 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'

No gene related to 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'.

Table S56.  Basic characteristics of clinical feature: 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'

HISTORY_HORMONAL_CONTRACEPTIVES_USE Labels N
  CURRENT USER 15
  FORMER USER 53
  NEVER USED 89
     
  Significant markers N = 0
Clinical variable #39: 'HEIGHT_CM_AT_DIAGNOSIS'

No gene related to 'HEIGHT_CM_AT_DIAGNOSIS'.

Table S57.  Basic characteristics of clinical feature: 'HEIGHT_CM_AT_DIAGNOSIS'

HEIGHT_CM_AT_DIAGNOSIS Mean (SD) 161.02 (7.3)
  Significant markers N = 0
Clinical variable #40: 'CORPUS_INVOLVEMENT'

No gene related to 'CORPUS_INVOLVEMENT'.

Table S58.  Basic characteristics of clinical feature: 'CORPUS_INVOLVEMENT'

CORPUS_INVOLVEMENT Labels N
  ABSENT 99
  PRESENT 18
     
  Significant markers N = 0
Clinical variable #41: 'CHEMO_CONCURRENT_TYPE'

No gene related to 'CHEMO_CONCURRENT_TYPE'.

Table S59.  Basic characteristics of clinical feature: 'CHEMO_CONCURRENT_TYPE'

CHEMO_CONCURRENT_TYPE Labels N
  CARBOPLATIN 3
  CISPLATIN 18
  OTHER 1
     
  Significant markers N = 0
Clinical variable #42: 'CERVIX_SUV_RESULTS'

No gene related to 'CERVIX_SUV_RESULTS'.

Table S60.  Basic characteristics of clinical feature: 'CERVIX_SUV_RESULTS'

CERVIX_SUV_RESULTS Mean (SD) 13.22 (7.2)
  Significant markers N = 0
Clinical variable #43: 'AJCC_TUMOR_PATHOLOGIC_PT'

30 genes related to 'AJCC_TUMOR_PATHOLOGIC_PT'.

Table S61.  Basic characteristics of clinical feature: 'AJCC_TUMOR_PATHOLOGIC_PT'

AJCC_TUMOR_PATHOLOGIC_PT Labels N
  T1A1 1
  T1B 36
  T1B1 72
  T1B2 31
  T2 6
  T2A 10
  T2A1 7
  T2A2 10
  T2B 37
  T3 2
  T3A 2
  T3B 17
  T4 10
  TIS 1
  TX 17
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'AJCC_TUMOR_PATHOLOGIC_PT'

Table S62.  Get Full Table List of top 10 genes differentially expressed by 'AJCC_TUMOR_PATHOLOGIC_PT'

kruskal_wallis_P Q
CATSPERB 4.173e-07 0.0016
AP4E1__1 5.356e-07 0.0016
LOC100132724 5.356e-07 0.0016
C8ORF77 5.446e-07 0.0016
ZNF252 5.446e-07 0.0016
DKFZP586I1420 6.509e-07 0.0016
LOC389791 6.904e-07 0.0016
PTGES2 6.904e-07 0.0016
LOC441208 8.086e-07 0.0016
C10ORF75 8.474e-07 0.0016
Clinical variable #44: 'AGE_AT_DIAGNOSIS'

30 genes related to 'AGE_AT_DIAGNOSIS'.

Table S63.  Basic characteristics of clinical feature: 'AGE_AT_DIAGNOSIS'

AGE_AT_DIAGNOSIS Mean (SD) 48.21 (14)
  Significant markers N = 30
  pos. correlated 12
  neg. correlated 18
List of top 10 genes differentially expressed by 'AGE_AT_DIAGNOSIS'

Table S64.  Get Full Table List of top 10 genes significantly correlated to 'AGE_AT_DIAGNOSIS' by Spearman correlation test

SpearmanCorr corrP Q
C21ORF34 -0.3115 2.902e-08 0.000193
MIR99A -0.3115 2.902e-08 0.000193
MIRLET7C -0.3115 2.902e-08 0.000193
GLDC 0.3074 4.492e-08 0.000196
MDFI 0.3053 5.582e-08 0.000196
CHRNB1 0.3048 5.889e-08 0.000196
C10ORF67 0.3016 8.181e-08 0.000208
SP4 -0.3015 8.342e-08 0.000208
RARB -0.295 1.605e-07 0.000356
CCDC23 -0.2882 3.159e-07 0.000565
Clinical variable #45: 'STAGE_EVENT.CLINICAL_STAGE'

30 genes related to 'STAGE_EVENT.CLINICAL_STAGE'.

Table S65.  Basic characteristics of clinical feature: 'STAGE_EVENT.CLINICAL_STAGE'

STAGE_EVENT.CLINICAL_STAGE Labels N
  STAGE I 5
  STAGE IA 1
  STAGE IA1 1
  STAGE IA2 1
  STAGE IB 37
  STAGE IB1 78
  STAGE IB2 38
  STAGE II 5
  STAGE IIA 9
  STAGE IIA1 5
  STAGE IIA2 7
  STAGE IIB 43
  STAGE III 1
  STAGE IIIA 3
  STAGE IIIB 42
  STAGE IVA 9
  STAGE IVB 12
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'STAGE_EVENT.CLINICAL_STAGE'

Table S66.  Get Full Table List of top 10 genes differentially expressed by 'STAGE_EVENT.CLINICAL_STAGE'

kruskal_wallis_P Q
ARF4 8.88e-06 0.0366
DPY30 1.103e-05 0.0366
TMEM50A 1.16e-05 0.0366
C3ORF48 1.193e-05 0.0366
RAB5A 1.193e-05 0.0366
ZNF322B 1.304e-05 0.0366
WDR55 1.531e-05 0.0366
POU2F1 1.654e-05 0.0366
PSMA3 1.794e-05 0.0366
PDE1B 2.114e-05 0.0366
Methods & Data
Input

  • Expresson data file = CESC-TP.meth.by_min_clin_corr.data.txt

  • Clinical data file = CESC-TP.merged_data.txt

  • Number of patients = 304

  • Number of genes = 19994

  • Number of clinical features = 45

Selected clinical features

  • For clinical features selected for this analysis and their value conozzle.versions, please find a documentation on selected CDEs .

  • Survival time data

    • Survival time data is a combined value of days_to_death and days_to_last_followup. For each patient, it creates a combined value 'days_to_death_or_last_fup' using conversion process below.

      • if 'vital_status'==1(dead), 'days_to_last_followup' is always NA. Thus, uses 'days_to_death' value for 'days_to_death_or_fup'

      • if 'vital_status'==0(alive),

        • if 'days_to_death'==NA & 'days_to_last_followup'!=NA, uses 'days_to_last_followup' value for 'days_to_death_or_fup'

        • if 'days_to_death'!=NA, excludes this case in survival analysis and report the case.

      • if 'vital_status'==NA,excludes this case in survival analysis and report the case.

    • cf. In certain diesase types such as SKCM, days_to_death parameter is replaced with time_from_specimen_dx or time_from_specimen_procurement_to_death .

  • This analysis excluded clinical variables that has only NA values.

Survival analysis

For survival clinical features, Wald's test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values using the 'coxph' function in R. Kaplan-Meier survival curves were plot using the four quartile subgroups of patients based on expression levels

Correlation analysis

For continuous numerical clinical features, Spearman's rank correlation coefficients (Spearman 1904) and two-tailed P values were estimated using 'cor.test' function in R

Wilcoxon rank sum test (Mann-Whitney U test)

For two groups (mutant or wild-type) of continuous type of clinical data, wilcoxon rank sum test (Mann and Whitney, 1947) was applied to compare their mean difference using 'wilcox.test(continuous.clinical ~ as.factor(group), exact=FALSE)' function in R. This test is equivalent to the Mann-Whitney test.

Q value calculation

For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.

References
[1] Andersen and Gill, Cox's regression model for counting processes, a large sample study, Annals of Statistics 10(4):1100-1120 (1982)
[2] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[3] Mann and Whitney, On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other, Annals of Mathematical Statistics 18 (1), 50-60 (1947)
[4] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)
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