Correlation between copy number variation genes (focal events) and molecular subtypes

Overview

Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and molecular subtypes.

Summary

Testing the association between copy number variation 12 focal events and 8 molecular subtypes across 123 patients, 28 significant findings detected with P value < 0.05 and Q value < 0.25.

del_3p22.2 cnv correlated to 'CN_CNMF', 'METHLYATION_CNMF', and 'MIRSEQ_MATURE_CNMF'.
del_6p25.2 cnv correlated to 'CN_CNMF', 'METHLYATION_CNMF', 'MRNASEQ_CNMF', 'MRNASEQ_CHIERARCHICAL', 'MIRSEQ_CNMF', and 'MIRSEQ_MATURE_CNMF'.
del_6q21 cnv correlated to 'CN_CNMF', 'METHLYATION_CNMF', 'MRNASEQ_CNMF', 'MRNASEQ_CHIERARCHICAL', 'MIRSEQ_CNMF', 'MIRSEQ_CHIERARCHICAL', 'MIRSEQ_MATURE_CNMF', and 'MIRSEQ_MATURE_CHIERARCHICAL'.
del_7q36.3 cnv correlated to 'MRNASEQ_CNMF'.
del_9p21.3 cnv correlated to 'MRNASEQ_CNMF', 'MRNASEQ_CHIERARCHICAL', and 'MIRSEQ_CHIERARCHICAL'.
del_11q22.1 cnv correlated to 'CN_CNMF', 'METHLYATION_CNMF', and 'MIRSEQ_MATURE_CNMF'.
del_19p13.11 cnv correlated to 'MRNASEQ_CNMF' and 'MRNASEQ_CHIERARCHICAL'.
del_22q12.1 cnv correlated to 'CN_CNMF'.
del_22q13.32 cnv correlated to 'CN_CNMF'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 12 focal events and 8 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 28 significant findings detected.


		Clinical Features	CN CNMF	METHLYATION CNMF	MRNASEQ CNMF	MRNASEQ CHIERARCHICAL	MIRSEQ CNMF	MIRSEQ CHIERARCHICAL	MIRSEQ MATURE CNMF	MIRSEQ MATURE CHIERARCHICAL
	nCNV (%)	nWild-Type	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test
del 6q21	20 (16%)	103	1e-05 (0.00096)	1e-05 (0.00096)	1e-05 (0.00096)	1e-05 (0.00096)	4e-05 (0.00332)	0.00015 (0.0115)	1e-05 (0.00096)	5e-05 (0.004)
del 6p25 2	26 (21%)	97	1e-05 (0.00096)	1e-05 (0.00096)	0.00149 (0.106)	6e-05 (0.00474)	0.0011 (0.0792)	0.00666 (0.426)	1e-05 (0.00096)	0.00515 (0.34)
del 3p22 2	14 (11%)	109	4e-05 (0.00332)	1e-05 (0.00096)	0.025 (1.00)	0.013 (0.779)	0.0237 (1.00)	0.065 (1.00)	0.00056 (0.0414)	0.0287 (1.00)
del 9p21 3	11 (9%)	112	0.0155 (0.913)	0.00427 (0.286)	4e-05 (0.00332)	1e-05 (0.00096)	0.56 (1.00)	0.00018 (0.0137)	0.142 (1.00)	0.0164 (0.95)
del 11q22 1	7 (6%)	116	6e-05 (0.00474)	1e-05 (0.00096)	0.0252 (1.00)	0.00847 (0.534)	0.0329 (1.00)	0.114 (1.00)	0.00236 (0.165)	0.0088 (0.546)
del 19p13 11	5 (4%)	118	0.259 (1.00)	0.045 (1.00)	0.00296 (0.204)	0.0004 (0.03)	0.725 (1.00)	0.00528 (0.343)	0.575 (1.00)	0.17 (1.00)
del 7q36 3	3 (2%)	120	0.0608 (1.00)	0.176 (1.00)	0.00101 (0.0737)	0.00412 (0.28)	0.651 (1.00)	0.117 (1.00)	0.104 (1.00)	0.621 (1.00)
del 22q12 1	19 (15%)	104	1e-05 (0.00096)	0.0127 (0.774)	0.0199 (1.00)	0.13 (1.00)	0.248 (1.00)	0.457 (1.00)	0.523 (1.00)	0.428 (1.00)
del 22q13 32	15 (12%)	108	2e-05 (0.00168)	0.0856 (1.00)	0.0676 (1.00)	0.0194 (1.00)	0.209 (1.00)	0.297 (1.00)	0.196 (1.00)	0.899 (1.00)
del 2q37 1	5 (4%)	118	0.258 (1.00)	0.0459 (1.00)	0.67 (1.00)	0.317 (1.00)	1 (1.00)	0.02 (1.00)	1 (1.00)	0.17 (1.00)
del 9q22 33	3 (2%)	120	0.598 (1.00)	0.176 (1.00)	0.0334 (1.00)	0.0325 (1.00)	0.196 (1.00)	0.0657 (1.00)	0.107 (1.00)	0.0596 (1.00)
del 10q26 3	6 (5%)	117	0.627 (1.00)	0.0393 (1.00)	0.0746 (1.00)	0.232 (1.00)	0.737 (1.00)	0.0667 (1.00)	0.858 (1.00)	0.0483 (1.00)

'del_3p22.2' versus 'CN_CNMF'

P value = 4e-05 (Fisher's exact test), Q value = 0.0033

Table S1. Gene #2: 'del_3p22.2' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	65	31	27
DEL PEAK 2(3P22.2) MUTATED	1	10	3
DEL PEAK 2(3P22.2) WILD-TYPE	64	21	24

Figure S1. Get High-res Image Gene #2: 'del_3p22.2' versus Molecular Subtype #1: 'CN_CNMF'

'del_3p22.2' versus 'METHLYATION_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S2. Gene #2: 'del_3p22.2' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	39	36	24	24
DEL PEAK 2(3P22.2) MUTATED	0	3	10	1
DEL PEAK 2(3P22.2) WILD-TYPE	39	33	14	23

Figure S2. Get High-res Image Gene #2: 'del_3p22.2' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'del_3p22.2' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.00056 (Fisher's exact test), Q value = 0.041

Table S3. Gene #2: 'del_3p22.2' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	18	59	46
DEL PEAK 2(3P22.2) MUTATED	0	2	12
DEL PEAK 2(3P22.2) WILD-TYPE	18	57	34

Figure S3. Get High-res Image Gene #2: 'del_3p22.2' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

'del_6p25.2' versus 'CN_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S4. Gene #3: 'del_6p25.2' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	65	31	27
DEL PEAK 3(6P25.2) MUTATED	1	20	5
DEL PEAK 3(6P25.2) WILD-TYPE	64	11	22

Figure S4. Get High-res Image Gene #3: 'del_6p25.2' versus Molecular Subtype #1: 'CN_CNMF'

'del_6p25.2' versus 'METHLYATION_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S5. Gene #3: 'del_6p25.2' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	39	36	24	24
DEL PEAK 3(6P25.2) MUTATED	2	6	15	3
DEL PEAK 3(6P25.2) WILD-TYPE	37	30	9	21

Figure S5. Get High-res Image Gene #3: 'del_6p25.2' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'del_6p25.2' versus 'MRNASEQ_CNMF'

P value = 0.00149 (Fisher's exact test), Q value = 0.11

Table S6. Gene #3: 'del_6p25.2' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	43	30	13	29
DEL PEAK 3(6P25.2) MUTATED	14	4	6	1
DEL PEAK 3(6P25.2) WILD-TYPE	29	26	7	28

Figure S6. Get High-res Image Gene #3: 'del_6p25.2' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

'del_6p25.2' versus 'MRNASEQ_CHIERARCHICAL'

P value = 6e-05 (Fisher's exact test), Q value = 0.0047

Table S7. Gene #3: 'del_6p25.2' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	44	41	20	10
DEL PEAK 3(6P25.2) MUTATED	15	4	0	6
DEL PEAK 3(6P25.2) WILD-TYPE	29	37	20	4

Figure S7. Get High-res Image Gene #3: 'del_6p25.2' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'del_6p25.2' versus 'MIRSEQ_CNMF'

P value = 0.0011 (Fisher's exact test), Q value = 0.079

Table S8. Gene #3: 'del_6p25.2' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5
ALL	58	61	1	2	1
DEL PEAK 3(6P25.2) MUTATED	20	5	0	1	0
DEL PEAK 3(6P25.2) WILD-TYPE	38	56	1	1	1

Figure S8. Get High-res Image Gene #3: 'del_6p25.2' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

'del_6p25.2' versus 'MIRSEQ_MATURE_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S9. Gene #3: 'del_6p25.2' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	18	59	46
DEL PEAK 3(6P25.2) MUTATED	1	5	20
DEL PEAK 3(6P25.2) WILD-TYPE	17	54	26

Figure S9. Get High-res Image Gene #3: 'del_6p25.2' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

'del_6q21' versus 'CN_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S10. Gene #4: 'del_6q21' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	65	31	27
DEL PEAK 4(6Q21) MUTATED	0	18	2
DEL PEAK 4(6Q21) WILD-TYPE	65	13	25

Figure S10. Get High-res Image Gene #4: 'del_6q21' versus Molecular Subtype #1: 'CN_CNMF'

'del_6q21' versus 'METHLYATION_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S11. Gene #4: 'del_6q21' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	39	36	24	24
DEL PEAK 4(6Q21) MUTATED	1	3	16	0
DEL PEAK 4(6Q21) WILD-TYPE	38	33	8	24

Figure S11. Get High-res Image Gene #4: 'del_6q21' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'del_6q21' versus 'MRNASEQ_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S12. Gene #4: 'del_6q21' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	43	30	13	29
DEL PEAK 4(6Q21) MUTATED	13	0	7	0
DEL PEAK 4(6Q21) WILD-TYPE	30	30	6	29

Figure S12. Get High-res Image Gene #4: 'del_6q21' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

'del_6q21' versus 'MRNASEQ_CHIERARCHICAL'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S13. Gene #4: 'del_6q21' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	44	41	20	10
DEL PEAK 4(6Q21) MUTATED	14	0	1	5
DEL PEAK 4(6Q21) WILD-TYPE	30	41	19	5

Figure S13. Get High-res Image Gene #4: 'del_6q21' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'del_6q21' versus 'MIRSEQ_CNMF'

P value = 4e-05 (Fisher's exact test), Q value = 0.0033

Table S14. Gene #4: 'del_6q21' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5
ALL	58	61	1	2	1
DEL PEAK 4(6Q21) MUTATED	18	1	0	1	0
DEL PEAK 4(6Q21) WILD-TYPE	40	60	1	1	1

Figure S14. Get High-res Image Gene #4: 'del_6q21' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

'del_6q21' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.00015 (Fisher's exact test), Q value = 0.012

Table S15. Gene #4: 'del_6q21' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5	CLUS_6
ALL	27	18	28	7	16	27
DEL PEAK 4(6Q21) MUTATED	9	0	7	3	1	0
DEL PEAK 4(6Q21) WILD-TYPE	18	18	21	4	15	27

Figure S15. Get High-res Image Gene #4: 'del_6q21' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

'del_6q21' versus 'MIRSEQ_MATURE_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S16. Gene #4: 'del_6q21' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	18	59	46
DEL PEAK 4(6Q21) MUTATED	0	0	20
DEL PEAK 4(6Q21) WILD-TYPE	18	59	26

Figure S16. Get High-res Image Gene #4: 'del_6q21' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

'del_6q21' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 5e-05 (Fisher's exact test), Q value = 0.004

Table S17. Gene #4: 'del_6q21' versus Molecular Subtype #8: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	29	33	33	28
DEL PEAK 4(6Q21) MUTATED	10	1	9	0
DEL PEAK 4(6Q21) WILD-TYPE	19	32	24	28

Figure S17. Get High-res Image Gene #4: 'del_6q21' versus Molecular Subtype #8: 'MIRSEQ_MATURE_CHIERARCHICAL'

'del_7q36.3' versus 'MRNASEQ_CNMF'

P value = 0.00101 (Fisher's exact test), Q value = 0.074

Table S18. Gene #5: 'del_7q36.3' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	43	30	13	29
DEL PEAK 5(7Q36.3) MUTATED	0	0	3	0
DEL PEAK 5(7Q36.3) WILD-TYPE	43	30	10	29

Figure S18. Get High-res Image Gene #5: 'del_7q36.3' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

'del_9p21.3' versus 'MRNASEQ_CNMF'

P value = 4e-05 (Fisher's exact test), Q value = 0.0033

Table S19. Gene #6: 'del_9p21.3' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	43	30	13	29
DEL PEAK 6(9P21.3) MUTATED	1	3	6	0
DEL PEAK 6(9P21.3) WILD-TYPE	42	27	7	29

Figure S19. Get High-res Image Gene #6: 'del_9p21.3' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

'del_9p21.3' versus 'MRNASEQ_CHIERARCHICAL'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S20. Gene #6: 'del_9p21.3' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	44	41	20	10
DEL PEAK 6(9P21.3) MUTATED	1	0	3	6
DEL PEAK 6(9P21.3) WILD-TYPE	43	41	17	4

Figure S20. Get High-res Image Gene #6: 'del_9p21.3' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'del_9p21.3' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.00018 (Fisher's exact test), Q value = 0.014

Table S21. Gene #6: 'del_9p21.3' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5	CLUS_6
ALL	27	18	28	7	16	27
DEL PEAK 6(9P21.3) MUTATED	0	0	3	4	3	1
DEL PEAK 6(9P21.3) WILD-TYPE	27	18	25	3	13	26

Figure S21. Get High-res Image Gene #6: 'del_9p21.3' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

'del_11q22.1' versus 'CN_CNMF'

P value = 6e-05 (Fisher's exact test), Q value = 0.0047

Table S22. Gene #9: 'del_11q22.1' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	65	31	27
DEL PEAK 9(11Q22.1) MUTATED	0	7	0
DEL PEAK 9(11Q22.1) WILD-TYPE	65	24	27

Figure S22. Get High-res Image Gene #9: 'del_11q22.1' versus Molecular Subtype #1: 'CN_CNMF'

'del_11q22.1' versus 'METHLYATION_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S23. Gene #9: 'del_11q22.1' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	39	36	24	24
DEL PEAK 9(11Q22.1) MUTATED	0	0	7	0
DEL PEAK 9(11Q22.1) WILD-TYPE	39	36	17	24

Figure S23. Get High-res Image Gene #9: 'del_11q22.1' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'del_11q22.1' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.00236 (Fisher's exact test), Q value = 0.17

Table S24. Gene #9: 'del_11q22.1' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	18	59	46
DEL PEAK 9(11Q22.1) MUTATED	0	0	7
DEL PEAK 9(11Q22.1) WILD-TYPE	18	59	39

Figure S24. Get High-res Image Gene #9: 'del_11q22.1' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

'del_19p13.11' versus 'MRNASEQ_CNMF'

P value = 0.00296 (Fisher's exact test), Q value = 0.2

Table S25. Gene #10: 'del_19p13.11' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	43	30	13	29
DEL PEAK 10(19P13.11) MUTATED	0	2	3	0
DEL PEAK 10(19P13.11) WILD-TYPE	43	28	10	29

Figure S25. Get High-res Image Gene #10: 'del_19p13.11' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

'del_19p13.11' versus 'MRNASEQ_CHIERARCHICAL'

P value = 4e-04 (Fisher's exact test), Q value = 0.03

Table S26. Gene #10: 'del_19p13.11' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	44	41	20	10
DEL PEAK 10(19P13.11) MUTATED	0	0	2	3
DEL PEAK 10(19P13.11) WILD-TYPE	44	41	18	7

Figure S26. Get High-res Image Gene #10: 'del_19p13.11' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'del_22q12.1' versus 'CN_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.00096

Table S27. Gene #11: 'del_22q12.1' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	65	31	27
DEL PEAK 11(22Q12.1) MUTATED	0	4	15
DEL PEAK 11(22Q12.1) WILD-TYPE	65	27	12

Figure S27. Get High-res Image Gene #11: 'del_22q12.1' versus Molecular Subtype #1: 'CN_CNMF'

'del_22q13.32' versus 'CN_CNMF'

P value = 2e-05 (Fisher's exact test), Q value = 0.0017

Table S28. Gene #12: 'del_22q13.32' versus Molecular Subtype #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	65	31	27
DEL PEAK 12(22Q13.32) MUTATED	1	4	10
DEL PEAK 12(22Q13.32) WILD-TYPE	64	27	17

Figure S28. Get High-res Image Gene #12: 'del_22q13.32' versus Molecular Subtype #1: 'CN_CNMF'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Molecular subtype file = THYM-TP.transferedmergedcluster.txt
Number of patients = 123
Number of significantly focal cnvs = 12
Number of molecular subtypes = 8
Exclude genes that fewer than K tumors have alterations, K = 3

Fisher's exact test

For binary or multi-class clinical features (nominal or ordinal), two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.test' function in R

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] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)

[2] 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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