Correlation between mRNAseq expression and clinical features

Overview

Introduction

This pipeline uses various statistical tests to identify mRNAs whose log2 expression levels correlated to selected clinical features. The input file "CESC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt" is generated in the pipeline mRNAseq_Preprocess in the stddata run.

Summary

Testing the association between 18187 genes and 39 clinical features across 304 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 23 clinical features related to at least one genes.

30 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

EAF2|55840 , SSBP3|23648 , NCAPH2|29781 , PRSS36|146547 , CXORF42|158801 , ...

30 genes correlated to 'YEARS_TO_BIRTH'.

NXNL2|158046 , LANCL1|10314 , CORO6|84940 , PGR|5241 , RHOF|54509 , ...

30 genes correlated to 'PATHOLOGY_T_STAGE'.

FBXL18|80028 , CYB561D1|284613 , TRIM25|7706 , PPFIA4|8497 , TMEM220|388335 , ...

1 gene correlated to 'PATHOLOGY_M_STAGE'.

ZFAND6|54469

30 genes correlated to 'RADIATION_THERAPY'.

EXOSC9|5393 , HADH|3033 , LHX4|89884 , PAG1|55824 , HNRNPD|3184 , ...

30 genes correlated to 'HISTOLOGICAL_TYPE'.

TP63|8626 , DDAH1|23576 , C3ORF54|389119 , BICD2|23299 , EPCAM|4072 , ...

30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

KLRG2|346689 , FLJ35390|255031 , TMPRSS3|64699 , A2ML1|144568 , APC2|10297 , ...

6 genes correlated to 'RACE'.

XKR9|389668 , LOC90784|90784 , POM121L10P|646074 , RNF112|7732 , DLX3|1747 , ...

30 genes correlated to 'WEIGHT_KG_AT_DIAGNOSIS'.

BLOC1S1|2647 , IL17RA|23765 , NUBP1|4682 , GNRHR2|114814 , IK|3550 , ...

30 genes correlated to 'TUMOR_STATUS'.

S1PR4|8698 , SOCS5|9655 , IFI30|10437 , RHOH|399 , MPND|84954 , ...

30 genes correlated to 'NEOPLASM_HISTOLOGIC_GRADE'.

ABLIM1|3983 , FUT2|2524 , FUT6|2528 , CDS1|1040 , CLINT1|9685 , ...

30 genes correlated to 'TOBACCO_SMOKING_HISTORY'.

GPR15|2838 , LRRC8A|56262 , C1ORF127|148345 , GPBAR1|151306 , HSD3B7|80270 , ...

1 gene correlated to 'AGEBEGANSMOKINGINYEARS'.

GAD1|2571

30 genes correlated to 'PREGNANCIES_COUNT_LIVE_BIRTH'.

ENPP3|5169 , RPL19P12|100129424 , SDCBP|6386 , FLJ44635|392490 , FAM35B2|439965 , ...

30 genes correlated to 'MENOPAUSE_STATUS'.

RIMBP3|85376 , RIMBP3C|150221 , RARB|5915 , RPF1|80135 , C1ORF52|148423 , ...

7 genes correlated to 'LYMPHOVASCULAR_INVOLVEMENT'.

TBCE|6905 , EXOG|9941 , MRPL30|51263 , LOC255167|255167 , SUSD4|55061 , ...

30 genes correlated to 'LYMPH_NODES_EXAMINED_HE_COUNT'.

KLRG2|346689 , FLJ35390|255031 , TMPRSS3|64699 , A2ML1|144568 , APC2|10297 , ...

30 genes correlated to 'KERATINIZATION_SQUAMOUS_CELL'.

QKI|9444 , SYT17|51760 , MAP7D3|79649 , SPG7|6687 , C9ORF30|91283 , ...

30 genes correlated to 'INITIAL_PATHOLOGIC_DX_YEAR'.

?|390284 , RPPH1|85495 , SNAPC5|10302 , C19ORF33|64073 , POM121L8P|29797 , ...

30 genes correlated to 'HEIGHT_CM_AT_DIAGNOSIS'.

RRAD|6236 , C19ORF33|64073 , ZNF107|51427 , ?|390284 , FOSB|2354 , ...

1 gene correlated to 'CERVIX_SUV_RESULTS'.

HDHD1A|8226

30 genes correlated to 'AGE_AT_DIAGNOSIS'.

NXNL2|158046 , PGR|5241 , RHOF|54509 , CORO6|84940 , GPR97|222487 , ...

30 genes correlated to 'CLINICAL_STAGE'.

TRIM25|7706 , FBXL18|80028 , RGS1|5996 , ZC3HAV1|56829 , PPFIA4|8497 , ...

No genes correlated to 'PATHOLOGY_N_STAGE', 'NUMBER_PACK_YEARS_SMOKED', 'ETHNICITY', 'TOBACCO_SMOKING_YEAR_STOPPED', 'TOBACCO_SMOKING_PACK_YEARS_SMOKED', 'RADIATION_THERAPY_STATUS', 'PREGNANCIES_COUNT_TOTAL', 'PREGNANCIES_COUNT_STILLBIRTH', 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT', 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT', 'PREGNANCIES_COUNT_ECTOPIC', 'POS_LYMPH_NODE_LOCATION', 'LYMPH_NODES_EXAMINED', 'HISTORY_HORMONAL_CONTRACEPTIVES_USE', 'CORPUS_INVOLVEMENT', and 'CHEMO_CONCURRENT_TYPE'.

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=30		N=NA		N=NA
YEARS_TO_BIRTH	Spearman correlation test	N=30	older	N=15	younger	N=15
PATHOLOGY_T_STAGE	Spearman correlation test	N=30	higher stage	N=17	lower stage	N=13
PATHOLOGY_N_STAGE	Wilcoxon test	N=0
PATHOLOGY_M_STAGE	Wilcoxon test	N=1	class1	N=1	class0	N=0
RADIATION_THERAPY	Wilcoxon test	N=30	yes	N=30	no	N=0
HISTOLOGICAL_TYPE	Kruskal-Wallis test	N=30
NUMBER_PACK_YEARS_SMOKED	Spearman correlation test	N=0
NUMBER_OF_LYMPH_NODES	Spearman correlation test	N=30	higher number_of_lymph_nodes	N=19	lower number_of_lymph_nodes	N=11
RACE	Kruskal-Wallis test	N=6
ETHNICITY	Wilcoxon test	N=0
WEIGHT_KG_AT_DIAGNOSIS	Spearman correlation test	N=30	higher weight_kg_at_diagnosis	N=22	lower weight_kg_at_diagnosis	N=8
TUMOR_STATUS	Wilcoxon test	N=30	with tumor	N=30	tumor free	N=0
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	Spearman correlation test	N=30	higher tobacco_smoking_history	N=16	lower tobacco_smoking_history	N=14
AGEBEGANSMOKINGINYEARS	Spearman correlation test	N=1	higher agebegansmokinginyears	N=1	lower agebegansmokinginyears	N=0
RADIATION_THERAPY_STATUS	Wilcoxon test	N=0
PREGNANCIES_COUNT_TOTAL	Spearman correlation test	N=0
PREGNANCIES_COUNT_STILLBIRTH	Spearman correlation test	N=0
PREGNANCY_SPONTANEOUS_ABORTION_COUNT	Spearman correlation test	N=0
PREGNANCIES_COUNT_LIVE_BIRTH	Spearman correlation test	N=30	higher pregnancies_count_live_birth	N=5	lower pregnancies_count_live_birth	N=25
PREGNANCY_THERAPEUTIC_ABORTION_COUNT	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=7	present	N=7	absent	N=0
LYMPH_NODES_EXAMINED_HE_COUNT	Spearman correlation test	N=30	higher lymph_nodes_examined_he_count	N=19	lower lymph_nodes_examined_he_count	N=11
LYMPH_NODES_EXAMINED	Spearman correlation test	N=0
KERATINIZATION_SQUAMOUS_CELL	Wilcoxon test	N=30	non-keratinizing squamous cell carcinoma	N=30	keratinizing squamous cell carcinoma	N=0
INITIAL_PATHOLOGIC_DX_YEAR	Spearman correlation test	N=30	higher initial_pathologic_dx_year	N=10	lower initial_pathologic_dx_year	N=20
HISTORY_HORMONAL_CONTRACEPTIVES_USE	Kruskal-Wallis test	N=0
HEIGHT_CM_AT_DIAGNOSIS	Spearman correlation test	N=30	higher height_cm_at_diagnosis	N=20	lower height_cm_at_diagnosis	N=10
CORPUS_INVOLVEMENT	Wilcoxon test	N=0
CHEMO_CONCURRENT_TYPE	Kruskal-Wallis test	N=0
CERVIX_SUV_RESULTS	Spearman correlation test	N=1	higher cervix_suv_results	N=1	lower cervix_suv_results	N=0
AGE_AT_DIAGNOSIS	Spearman correlation test	N=30	higher age_at_diagnosis	N=15	lower age_at_diagnosis	N=15
CLINICAL_STAGE	Kruskal-Wallis test	N=30

Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

30 genes 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)	0.1-210.7 (median=23.2)
	censored	N = 231
	death	N = 72

	Significant markers	N = 30
	associated with shorter survival	NA
	associated with longer survival	NA

List of top 10 genes differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2. Get Full Table List of top 10 genes significantly associated with 'Time to Death' by Cox regression test. For the survival curves, it compared quantile intervals at c(0, 0.25, 0.50, 0.75, 1) and did not try survival analysis if there is only one interval.

	logrank_P	Q	C_index
EAF2\|55840	2.42e-06	0.03	0.328
SSBP3\|23648	3.99e-06	0.03	0.313
NCAPH2\|29781	6.79e-06	0.03	0.358
PRSS36\|146547	8.5e-06	0.03	0.304
CXORF42\|158801	9.57e-06	0.03	0.331
TTC16\|158248	1.14e-05	0.03	0.378
P4HA1\|5033	1.19e-05	0.03	0.666
TREX1\|11277	1.41e-05	0.03	0.311
GATS\|352954	1.51e-05	0.03	0.318
ESM1\|11082	2.01e-05	0.037	0.67

Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

Table S3. Basic characteristics of clinical feature: 'YEARS_TO_BIRTH'


YEARS_TO_BIRTH	Mean (SD)	48.16 (14)
	Significant markers	N = 30
	pos. correlated	15
	neg. correlated	15

List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

Table S4. Get Full Table List of top 10 genes significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

	SpearmanCorr	corrP	Q
NXNL2\|158046	-0.3781	7.084e-11	1.29e-06
LANCL1\|10314	0.3204	1.225e-08	0.000111
CORO6\|84940	-0.3165	1.888e-08	0.000114
PGR\|5241	-0.3142	2.534e-08	0.000115
RHOF\|54509	-0.3088	4.299e-08	0.000152
IL24\|11009	-0.3104	5.21e-08	0.000152
CSF3\|1440	-0.3086	6.975e-08	0.000152
GALNT11\|63917	0.3033	7.647e-08	0.000152
DIO2\|1734	-0.3019	8.821e-08	0.000152
GPR97\|222487	-0.3018	8.929e-08	0.000152

Clinical variable #3: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S5. Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'


PATHOLOGY_T_STAGE	Mean (SD)	1.59 (0.81)
		N
	T1	140
	T2	71
	T3	20
	T4	10

	Significant markers	N = 30
	pos. correlated	17
	neg. correlated	13

List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S6. Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
FBXL18\|80028	0.3693	3.346e-09	6.09e-05
CYB561D1\|284613	0.351	2.136e-08	0.00019
TRIM25\|7706	0.3447	3.97e-08	0.00019
PPFIA4\|8497	0.3432	4.577e-08	0.00019
TMEM220\|388335	-0.3418	5.215e-08	0.00019
ZC3HAV1\|56829	0.3293	1.674e-07	0.000507
ZNF487\|642819	-0.3115	8.985e-07	0.00233
CCNF\|899	0.3086	1.033e-06	0.00235
CIR1\|9541	-0.2999	2.134e-06	0.00428
PPIG\|9360	-0.2987	2.352e-06	0.00428

Clinical variable #4: 'PATHOLOGY_N_STAGE'

No gene related to 'PATHOLOGY_N_STAGE'.

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


PATHOLOGY_N_STAGE	Labels	N
	N0	133
	N1	60

	Significant markers	N = 0

Clinical variable #5: 'PATHOLOGY_M_STAGE'

One gene related to 'PATHOLOGY_M_STAGE'.

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


PATHOLOGY_M_STAGE	Labels	N
	class0	116
	class1	10

	Significant markers	N = 1
	Higher in class1	1
	Higher in class0	0

List of one gene differentially expressed by 'PATHOLOGY_M_STAGE'

Table S9. Get Full Table List of one gene differentially expressed by 'PATHOLOGY_M_STAGE'

	W(pos if higher in 'class1')	wilcoxontestP	Q	AUC
ZFAND6\|54469	94	1.177e-05	0.214	0.919

Clinical variable #6: 'RADIATION_THERAPY'

30 genes related to 'RADIATION_THERAPY'.

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


RADIATION_THERAPY	Labels	N
	NO	55
	YES	127

	Significant markers	N = 30
	Higher in YES	30
	Higher in NO	0

List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

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

	W(pos if higher in 'YES')	wilcoxontestP	Q	AUC
EXOSC9\|5393	2007	5.365e-06	0.0651	0.7127
HADH\|3033	2062	1.179e-05	0.0651	0.7048
LHX4\|89884	4536	1.26e-05	0.0651	0.7092
PAG1\|55824	4907	1.475e-05	0.0651	0.7025
HNRNPD\|3184	2092	1.791e-05	0.0651	0.7005
H3F3C\|440093	2113	2.387e-05	0.0724	0.6975
ZNFX1\|57169	4842	3.576e-05	0.0786	0.6932
DPH3B\|100132911	4678	4.252e-05	0.0786	0.693
AIMP1\|9255	2157	4.307e-05	0.0786	0.6912
CCDC111\|201973	2167	4.913e-05	0.0786	0.6898

Clinical variable #7: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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


HISTOLOGICAL_TYPE	Labels	N
	ADENOSQUAMOUS	5
	CERVICAL SQUAMOUS CELL CARCINOMA	252
	ENDOCERVICAL ADENOCARCINOMA OF THE USUAL TYPE	6
	ENDOCERVICAL TYPE OF ADENOCARCINOMA	21
	ENDOMETRIOID ADENOCARCINOMA OF ENDOCERVIX	3
	MUCINOUS ADENOCARCINOMA OF ENDOCERVICAL TYPE	17

	Significant markers	N = 30

List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S13. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

	kruskal_wallis_P	Q
TP63\|8626	6.172e-23	1.12e-18
DDAH1\|23576	1.488e-22	1.35e-18
C3ORF54\|389119	2.221e-22	1.35e-18
BICD2\|23299	3.995e-22	1.62e-18
EPCAM\|4072	4.44e-22	1.62e-18
CLCA2\|9635	5.404e-22	1.64e-18
CLDN3\|1365	7.534e-22	1.96e-18
GPR87\|53836	1.292e-21	2.59e-18
KRT6A\|3853	1.344e-21	2.59e-18
CSTA\|1475	1.422e-21	2.59e-18

Clinical variable #8: 'NUMBER_PACK_YEARS_SMOKED'

No gene related to 'NUMBER_PACK_YEARS_SMOKED'.

Table S14. 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 S15. Basic characteristics of clinical feature: 'NUMBER_OF_LYMPH_NODES'


NUMBER_OF_LYMPH_NODES	Mean (SD)	1.04 (2.4)
	Significant markers	N = 30
	pos. correlated	19
	neg. correlated	11

List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S16. Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

	SpearmanCorr	corrP	Q
KLRG2\|346689	0.3296	2.492e-05	0.124
FLJ35390\|255031	0.3219	3.499e-05	0.124
TMPRSS3\|64699	-0.3192	4.115e-05	0.124
A2ML1\|144568	0.3207	4.234e-05	0.124
APC2\|10297	0.3192	4.358e-05	0.124
SERPINB12\|89777	0.3899	4.668e-05	0.124
METTL8\|79828	0.3154	5.133e-05	0.124
NOTCH1\|4851	0.3119	6.274e-05	0.124
NCAM2\|4685	0.3275	7.365e-05	0.124
PHC2\|1912	-0.3089	7.447e-05	0.124

Clinical variable #10: 'RACE'

6 genes related to 'RACE'.

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


RACE	Labels	N
	AMERICAN INDIAN OR ALASKA NATIVE	7
	ASIAN	20
	BLACK OR AFRICAN AMERICAN	30
	NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	2
	WHITE	209

	Significant markers	N = 6

List of 6 genes differentially expressed by 'RACE'

Table S18. Get Full Table List of 6 genes differentially expressed by 'RACE'

	kruskal_wallis_P	Q
XKR9\|389668	1.623e-06	0.0295
LOC90784\|90784	3.317e-06	0.0302
POM121L10P\|646074	8.024e-06	0.0486
RNF112\|7732	1.518e-05	0.069
DLX3\|1747	2.571e-05	0.0935
RPS26\|6231	6.376e-05	0.193

Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S19. 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'

30 genes related to 'WEIGHT_KG_AT_DIAGNOSIS'.

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


WEIGHT_KG_AT_DIAGNOSIS	Mean (SD)	72.85 (22)
	Significant markers	N = 30
	pos. correlated	22
	neg. correlated	8

List of top 10 genes differentially expressed by 'WEIGHT_KG_AT_DIAGNOSIS'

Table S21. Get Full Table List of top 10 genes significantly correlated to 'WEIGHT_KG_AT_DIAGNOSIS' by Spearman correlation test

	SpearmanCorr	corrP	Q
BLOC1S1\|2647	0.3168	7.906e-08	0.00144
IL17RA\|23765	-0.2979	4.828e-07	0.00439
NUBP1\|4682	0.2931	7.486e-07	0.00454
GNRHR2\|114814	0.2873	1.262e-06	0.00574
IK\|3550	0.2846	1.609e-06	0.00585
TTPAL\|79183	-0.2824	1.947e-06	0.0059
ZRSR2\|8233	0.2796	2.478e-06	0.0061
SERINC3\|10955	-0.2787	2.684e-06	0.0061
NASP\|4678	0.2734	4.191e-06	0.00847
NCKAP1\|10787	-0.2704	5.403e-06	0.00983

Clinical variable #13: 'TUMOR_STATUS'

30 genes related to 'TUMOR_STATUS'.

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


TUMOR_STATUS	Labels	N
	TUMOR FREE	198
	WITH TUMOR	80

	Significant markers	N = 30
	Higher in WITH TUMOR	30
	Higher in TUMOR FREE	0

List of top 10 genes differentially expressed by 'TUMOR_STATUS'

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

	W(pos if higher in 'WITH TUMOR')	wilcoxontestP	Q	AUC
S1PR4\|8698	4798	2.694e-07	0.00478	0.6971
SOCS5\|9655	10960	5.484e-07	0.00478	0.6919
IFI30\|10437	4954	1.026e-06	0.00478	0.6872
RHOH\|399	4957	1.052e-06	0.00478	0.6871
MPND\|84954	5027	1.876e-06	0.00682	0.6826
ZBTB32\|27033	4990	4.767e-06	0.00791	0.6769
CD6\|923	5162	5.523e-06	0.00791	0.6741
SELPLG\|6404	5167	5.743e-06	0.00791	0.6738
LCK\|3932	5168	5.788e-06	0.00791	0.6737
CXCR6\|10663	5170	5.879e-06	0.00791	0.6736

Clinical variable #14: 'NEOPLASM_HISTOLOGIC_GRADE'

30 genes related to 'NEOPLASM_HISTOLOGIC_GRADE'.

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


NEOPLASM_HISTOLOGIC_GRADE	Labels	N
	G1	18
	G2	135
	G3	118
	G4	1
	GX	24

	Significant markers	N = 30

List of top 10 genes differentially expressed by 'NEOPLASM_HISTOLOGIC_GRADE'

Table S25. Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM_HISTOLOGIC_GRADE'

	kruskal_wallis_P	Q
ABLIM1\|3983	2.427e-07	0.00437
FUT2\|2524	6.054e-07	0.00437
FUT6\|2528	7.207e-07	0.00437
CDS1\|1040	3.937e-06	0.0179
CLINT1\|9685	7.02e-06	0.0205
ARHGEF37\|389337	7.164e-06	0.0205
WDR70\|55100	7.898e-06	0.0205
SOHLH2\|54937	1.135e-05	0.0236
FAHD2B\|151313	1.168e-05	0.0236
SCARNA2\|677766	1.69e-05	0.0307

Clinical variable #15: 'TOBACCO_SMOKING_YEAR_STOPPED'

No gene related to 'TOBACCO_SMOKING_YEAR_STOPPED'.

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


TOBACCO_SMOKING_YEAR_STOPPED	Mean (SD)	1999.7 (14)
	Significant markers	N = 0

Clinical variable #16: 'TOBACCO_SMOKING_PACK_YEARS_SMOKED'

No gene related to 'TOBACCO_SMOKING_PACK_YEARS_SMOKED'.

Table S27. 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 #17: 'TOBACCO_SMOKING_HISTORY'

30 genes related to 'TOBACCO_SMOKING_HISTORY'.

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


TOBACCO_SMOKING_HISTORY	Mean (SD)	1.84 (1.1)
	Value	N
	1	144
	2	64
	3	9
	4	40
	5	4

	Significant markers	N = 30
	pos. correlated	16
	neg. correlated	14

List of top 10 genes differentially expressed by 'TOBACCO_SMOKING_HISTORY'

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

	SpearmanCorr	corrP	Q
GPR15\|2838	0.3318	2.293e-06	0.0417
LRRC8A\|56262	0.2734	7.422e-06	0.0675
C1ORF127\|148345	-0.2467	6.198e-05	0.293
GPBAR1\|151306	-0.2425	7.551e-05	0.293
HSD3B7\|80270	-0.2396	9.282e-05	0.293
RLF\|6018	0.2309	0.0001674	0.293
REV1\|51455	0.2305	0.0001722	0.293
SPEN\|23013	0.2297	0.0001813	0.293
ZNF69\|7620	-0.2298	0.0001858	0.293
SERPINB5\|5268	0.2293	0.0001868	0.293

Clinical variable #18: 'AGEBEGANSMOKINGINYEARS'

One gene related to 'AGEBEGANSMOKINGINYEARS'.

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


AGEBEGANSMOKINGINYEARS	Mean (SD)	21.14 (7.7)
	Significant markers	N = 1
	pos. correlated	1
	neg. correlated	0

List of one gene differentially expressed by 'AGEBEGANSMOKINGINYEARS'

Table S31. Get Full Table List of one gene significantly correlated to 'AGEBEGANSMOKINGINYEARS' by Spearman correlation test

	SpearmanCorr	corrP	Q
GAD1\|2571	0.469	5.977e-06	0.109

Clinical variable #19: '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 #20: 'PREGNANCIES_COUNT_TOTAL'

No gene related to 'PREGNANCIES_COUNT_TOTAL'.

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


PREGNANCIES_COUNT_TOTAL	Mean (SD)	3.64 (2.6)
	Significant markers	N = 0

Clinical variable #21: 'PREGNANCIES_COUNT_STILLBIRTH'

No gene related to 'PREGNANCIES_COUNT_STILLBIRTH'.

Table S34. Basic characteristics of clinical feature: 'PREGNANCIES_COUNT_STILLBIRTH'


PREGNANCIES_COUNT_STILLBIRTH	Mean (SD)	0.07 (0.35)
	Value	N
	0	106
	1	5
	3	1

	Significant markers	N = 0

Clinical variable #22: 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT'

No gene related to 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT'.

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


PREGNANCY_SPONTANEOUS_ABORTION_COUNT	Mean (SD)	0.54 (0.95)
	Significant markers	N = 0

Clinical variable #23: 'PREGNANCIES_COUNT_LIVE_BIRTH'

30 genes related to 'PREGNANCIES_COUNT_LIVE_BIRTH'.

Table S36. 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	5
	neg. correlated	25

List of top 10 genes differentially expressed by 'PREGNANCIES_COUNT_LIVE_BIRTH'

Table S37. Get Full Table List of top 10 genes significantly correlated to 'PREGNANCIES_COUNT_LIVE_BIRTH' by Spearman correlation test

	SpearmanCorr	corrP	Q
ENPP3\|5169	-0.2737	2.894e-05	0.195
RPL19P12\|100129424	-0.255	3.178e-05	0.195
SDCBP\|6386	-0.2473	5.564e-05	0.195
FLJ44635\|392490	-0.2452	6.442e-05	0.195
FAM35B2\|439965	-0.2438	7.129e-05	0.195
POU2F1\|5451	-0.2435	7.247e-05	0.195
HSP90B3P\|343477	-0.2373	0.0001118	0.195
SLC43A1\|8501	-0.2346	0.0001344	0.195
C10ORF79\|80217	-0.2368	0.0001347	0.195
FANCG\|2189	0.2339	0.0001414	0.195

Clinical variable #24: 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT'

No gene related to 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT'.

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


PREGNANCY_THERAPEUTIC_ABORTION_COUNT	Mean (SD)	0.85 (1.8)
	Significant markers	N = 0

Clinical variable #25: 'PREGNANCIES_COUNT_ECTOPIC'

No gene related to 'PREGNANCIES_COUNT_ECTOPIC'.

Table S39. Basic characteristics of clinical feature: 'PREGNANCIES_COUNT_ECTOPIC'


PREGNANCIES_COUNT_ECTOPIC	Mean (SD)	0.11 (0.34)
	Value	N
	0	104
	1	11
	2	1

	Significant markers	N = 0

Clinical variable #26: 'POS_LYMPH_NODE_LOCATION'

No gene related to 'POS_LYMPH_NODE_LOCATION'.

Table S40. 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	40
	POSITIVE BLADDER MARGIN	1
	POSITIVE VAGINAL MARGIN	12

	Significant markers	N = 0

Clinical variable #27: 'MENOPAUSE_STATUS'

30 genes related to 'MENOPAUSE_STATUS'.

Table S41. Basic characteristics of clinical feature: 'MENOPAUSE_STATUS'


MENOPAUSE_STATUS	Labels	N
	INDETERMINATE (NEITHER PRE OR POSTMENOPAUSAL)	3
	PERI (6-12 MONTHS SINCE LAST MENSTRUAL PERIOD)	25
	POST (PRIOR BILATERAL OVARIECTOMY OR >12 MO SINCE LMP WITH NO PRIOR HYSTERECTOMY)	82
	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 S42. Get Full Table List of top 10 genes differentially expressed by 'MENOPAUSE_STATUS'

	kruskal_wallis_P	Q
RIMBP3\|85376	1.115e-07	0.00203
RIMBP3C\|150221	2.869e-06	0.0219
RARB\|5915	3.608e-06	0.0219
RPF1\|80135	1.121e-05	0.0492
C1ORF52\|148423	1.352e-05	0.0492
DIO2\|1734	1.756e-05	0.0532
PGR\|5241	3.059e-05	0.0795
HSFX2\|100130086	3.773e-05	0.0858
PPIH\|10465	4.843e-05	0.0886
PHGDH\|26227	4.873e-05	0.0886

Clinical variable #28: 'LYMPHOVASCULAR_INVOLVEMENT'

7 genes related to 'LYMPHOVASCULAR_INVOLVEMENT'.

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


LYMPHOVASCULAR_INVOLVEMENT	Labels	N
	ABSENT	71
	PRESENT	79

	Significant markers	N = 7
	Higher in PRESENT	7
	Higher in ABSENT	0

List of 7 genes differentially expressed by 'LYMPHOVASCULAR_INVOLVEMENT'

Table S44. Get Full Table List of 7 genes differentially expressed by 'LYMPHOVASCULAR_INVOLVEMENT'

	W(pos if higher in 'PRESENT')	wilcoxontestP	Q	AUC
TBCE\|6905	c("3980", "9.743e-06")	c("3980", "9.743e-06")	0.177	0.7096
EXOG\|9941	c("1673", "2.07e-05")	c("1673", "2.07e-05")	0.188	0.7017
MRPL30\|51263	c("3859", "7.268e-05")	c("3859", "7.268e-05")	0.297	0.688
LOC255167\|255167	c("2907", "7.819e-05")	c("2907", "7.819e-05")	0.297	0.7022
SUSD4\|55061	c("3838", "0.0001009")	c("3838", "0.0001009")	0.297	0.6843
LIMD1\|8994	c("1776", "0.0001091")	c("1776", "0.0001091")	0.297	0.6834
PHLDB3\|653583	c("3830", "0.0001142")	c("3830", "0.0001142")	0.297	0.6828

Clinical variable #29: 'LYMPH_NODES_EXAMINED_HE_COUNT'

30 genes related to 'LYMPH_NODES_EXAMINED_HE_COUNT'.

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


LYMPH_NODES_EXAMINED_HE_COUNT	Mean (SD)	1.04 (2.4)
	Significant markers	N = 30
	pos. correlated	19
	neg. correlated	11

List of top 10 genes differentially expressed by 'LYMPH_NODES_EXAMINED_HE_COUNT'

Table S46. Get Full Table List of top 10 genes significantly correlated to 'LYMPH_NODES_EXAMINED_HE_COUNT' by Spearman correlation test

	SpearmanCorr	corrP	Q
KLRG2\|346689	0.3296	2.492e-05	0.124
FLJ35390\|255031	0.3219	3.499e-05	0.124
TMPRSS3\|64699	-0.3192	4.115e-05	0.124
A2ML1\|144568	0.3207	4.234e-05	0.124
APC2\|10297	0.3192	4.358e-05	0.124
SERPINB12\|89777	0.3899	4.668e-05	0.124
METTL8\|79828	0.3154	5.133e-05	0.124
NOTCH1\|4851	0.3119	6.274e-05	0.124
NCAM2\|4685	0.3275	7.365e-05	0.124
PHC2\|1912	-0.3089	7.447e-05	0.124

Clinical variable #30: 'LYMPH_NODES_EXAMINED'

No gene related to 'LYMPH_NODES_EXAMINED'.

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


LYMPH_NODES_EXAMINED	Mean (SD)	22.35 (13)
	Significant markers	N = 0

Clinical variable #31: 'KERATINIZATION_SQUAMOUS_CELL'

30 genes related to 'KERATINIZATION_SQUAMOUS_CELL'.

Table S48. Basic characteristics of clinical feature: 'KERATINIZATION_SQUAMOUS_CELL'


KERATINIZATION_SQUAMOUS_CELL	Labels	N
	KERATINIZING SQUAMOUS CELL CARCINOMA	55
	NON-KERATINIZING SQUAMOUS CELL CARCINOMA	119

	Significant markers	N = 30
	Higher in NON-KERATINIZING SQUAMOUS CELL CARCINOMA	30
	Higher in KERATINIZING SQUAMOUS CELL CARCINOMA	0

List of top 10 genes differentially expressed by 'KERATINIZATION_SQUAMOUS_CELL'

Table S49. Get Full Table List of top 10 genes differentially expressed by 'KERATINIZATION_SQUAMOUS_CELL'

	W(pos if higher in 'NON-KERATINIZING SQUAMOUS CELL CARCINOMA')	wilcoxontestP	Q	AUC
QKI\|9444	1788	1.56e-06	0.0284	0.7268
SYT17\|51760	4616	1.38e-05	0.125	0.7053
MAP7D3\|79649	1975	2.691e-05	0.139	0.6982
SPG7\|6687	4561	3.059e-05	0.139	0.6969
C9ORF30\|91283	2029	5.738e-05	0.166	0.69
SFXN2\|118980	4512	6.062e-05	0.166	0.6894
FRAT2\|23401	4508	6.403e-05	0.166	0.6888
BCL2L2\|599	2088	0.0001269	0.194	0.681
JAZF1\|221895	2090	0.0001303	0.194	0.6807
TMEM180\|79847	4455	0.0001303	0.194	0.6807

Clinical variable #32: 'INITIAL_PATHOLOGIC_DX_YEAR'

30 genes related to 'INITIAL_PATHOLOGIC_DX_YEAR'.

Table S50. 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	10
	neg. correlated	20

List of top 10 genes differentially expressed by 'INITIAL_PATHOLOGIC_DX_YEAR'

Table S51. Get Full Table List of top 10 genes significantly correlated to 'INITIAL_PATHOLOGIC_DX_YEAR' by Spearman correlation test

	SpearmanCorr	corrP	Q
?\|390284	-0.2917	2.943e-07	0.00535
RPPH1\|85495	-0.2596	4.866e-06	0.037
SNAPC5\|10302	-0.2565	6.338e-06	0.037
C19ORF33\|64073	-0.2536	8.146e-06	0.037
POM121L8P\|29797	0.3038	4.159e-05	0.111
RCL1\|10171	-0.2332	4.272e-05	0.111
RPL36A\|6173	-0.2332	4.273e-05	0.111
LIMD1\|8994	0.2302	5.392e-05	0.113
C9ORF171\|389799	0.3228	5.602e-05	0.113
RPL13AP6\|644511	-0.2235	8.958e-05	0.15

Clinical variable #33: 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'

No gene related to 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'.

Table S52. 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 #34: 'HEIGHT_CM_AT_DIAGNOSIS'

30 genes related to 'HEIGHT_CM_AT_DIAGNOSIS'.

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


HEIGHT_CM_AT_DIAGNOSIS	Mean (SD)	161.01 (7.1)
	Significant markers	N = 30
	pos. correlated	20
	neg. correlated	10

List of top 10 genes differentially expressed by 'HEIGHT_CM_AT_DIAGNOSIS'

Table S54. Get Full Table List of top 10 genes significantly correlated to 'HEIGHT_CM_AT_DIAGNOSIS' by Spearman correlation test

	SpearmanCorr	corrP	Q
RRAD\|6236	0.2705	9.32e-06	0.0658
C19ORF33\|64073	0.2693	1.024e-05	0.0658
ZNF107\|51427	-0.265	1.437e-05	0.0658
?\|390284	0.2659	1.448e-05	0.0658
FOSB\|2354	0.2575	2.545e-05	0.0752
LOC541471\|541471	0.256	2.84e-05	0.0752
ANP32C\|23520	0.2582	3.113e-05	0.0752
DUSP1\|1843	0.254	3.306e-05	0.0752
SPAG7\|9552	0.2501	4.372e-05	0.0884
PLK3\|1263	0.2468	5.555e-05	0.101

Clinical variable #35: 'CORPUS_INVOLVEMENT'

No gene related to 'CORPUS_INVOLVEMENT'.

Table S55. Basic characteristics of clinical feature: 'CORPUS_INVOLVEMENT'


CORPUS_INVOLVEMENT	Labels	N
	ABSENT	99
	PRESENT	19

	Significant markers	N = 0

Clinical variable #36: 'CHEMO_CONCURRENT_TYPE'

No gene related to 'CHEMO_CONCURRENT_TYPE'.

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


CHEMO_CONCURRENT_TYPE	Labels	N
	CARBOPLATIN	7
	CISPLATIN	102
	OTHER	2

	Significant markers	N = 0

Clinical variable #37: 'CERVIX_SUV_RESULTS'

One gene related to 'CERVIX_SUV_RESULTS'.

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


CERVIX_SUV_RESULTS	Mean (SD)	13.22 (7.2)
	Significant markers	N = 1
	pos. correlated	1
	neg. correlated	0

List of one gene differentially expressed by 'CERVIX_SUV_RESULTS'

Table S58. Get Full Table List of one gene significantly correlated to 'CERVIX_SUV_RESULTS' by Spearman correlation test

	SpearmanCorr	corrP	Q
HDHD1A\|8226	0.848	0	0

Clinical variable #38: 'AGE_AT_DIAGNOSIS'

30 genes related to 'AGE_AT_DIAGNOSIS'.

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


AGE_AT_DIAGNOSIS	Mean (SD)	48.24 (14)
	Significant markers	N = 30
	pos. correlated	15
	neg. correlated	15

List of top 10 genes differentially expressed by 'AGE_AT_DIAGNOSIS'

Table S60. Get Full Table List of top 10 genes significantly correlated to 'AGE_AT_DIAGNOSIS' by Spearman correlation test

	SpearmanCorr	corrP	Q
NXNL2\|158046	-0.3808	4.636e-11	8.43e-07
PGR\|5241	-0.3177	1.569e-08	0.00012
RHOF\|54509	-0.3075	4.421e-08	0.00012
CORO6\|84940	-0.3074	4.461e-08	0.00012
GPR97\|222487	-0.3074	4.496e-08	0.00012
IL24\|11009	-0.3106	4.61e-08	0.00012
LANCL1\|10314	0.3071	4.634e-08	0.00012
CSF3\|1440	-0.3101	5.367e-08	0.000122
DIO2\|1734	-0.3032	6.946e-08	0.00014
RRAGD\|58528	0.2975	1.25e-07	0.000227

Clinical variable #39: 'CLINICAL_STAGE'

30 genes related to 'CLINICAL_STAGE'.

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


CLINICAL_STAGE	Labels	N
	STAGE I	5
	STAGE IA	1
	STAGE IA1	1
	STAGE IA2	1
	STAGE IB	38
	STAGE IB1	77
	STAGE IB2	39
	STAGE II	5
	STAGE IIA	9
	STAGE IIA1	5
	STAGE IIA2	7
	STAGE IIB	43
	STAGE III	1
	STAGE IIIA	2
	STAGE IIIB	42
	STAGE IVA	9
	STAGE IVB	12

	Significant markers	N = 30

List of top 10 genes differentially expressed by 'CLINICAL_STAGE'

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

	kruskal_wallis_P	Q
TRIM25\|7706	4.555e-09	8.28e-05
FBXL18\|80028	1.058e-07	9e-04
RGS1\|5996	1.875e-07	9e-04
ZC3HAV1\|56829	1.979e-07	9e-04
PPFIA4\|8497	6.372e-07	0.00232
CYB561D1\|284613	1.342e-05	0.0407
ZBTB3\|79842	1.719e-05	0.0447
TSC22D3\|1831	2.85e-05	0.0648
DNAJC5\|80331	3.861e-05	0.0771
APLN\|8862	4.241e-05	0.0771

Methods & Data

Input

Expresson data file = CESC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Clinical data file = CESC-TP.merged_data.txt
Number of patients = 304
Number of genes = 18187
Number of clinical features = 39

Selected clinical features

Further details on clinical features selected for this analysis, please find a documentation on selected CDEs (Clinical Data Elements). The first column of the file is a formula to convert values and the second column is a clinical parameter name.

There are also useful links about clinical features.

CDE Browser

Data dictionary for clinical data

NCI wiki - Biospecimen and Clinical XSD Files Specification

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, logrank test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values comparing quantile intervals using the 'coxph' function in R. Kaplan-Meier survival curves were plotted using quantile intervals at c(0, 0.25, 0.50, 0.75, 1). If there is only one interval group, it will not try survival analysis.

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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