Correlation between copy number variation genes (focal events) and selected clinical features

Thyroid Adenocarcinoma (Primary solid tumor)

16 April 2014 | analyses__2014_04_16

Maintainer Information

Citation Information

Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)

Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between copy number variation genes (focal events) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1BP01GR

Overview

Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and selected clinical features.

Summary

Testing the association between copy number variation 30 focal events and 15 clinical features across 484 patients, 12 significant findings detected with Q value < 0.25.

del_2p23.1 cnv correlated to 'NUMBER.OF.LYMPH.NODES'.
del_2q35 cnv correlated to 'NUMBER.OF.LYMPH.NODES'.
del_8p23.2 cnv correlated to 'NUMBER.OF.LYMPH.NODES'.
del_8p22 cnv correlated to 'NUMBER.OF.LYMPH.NODES'.
del_8p12 cnv correlated to 'NUMBER.OF.LYMPH.NODES'.
del_8q24.22 cnv correlated to 'NUMBER.OF.LYMPH.NODES'.
del_9q21.13 cnv correlated to 'NEOPLASM.DISEASESTAGE'.
del_11p15.1 cnv correlated to 'AGE' and 'NEOPLASM.DISEASESTAGE'.
del_18q22.2 cnv correlated to 'NUMBER.OF.LYMPH.NODES'.
del_xq22.3 cnv correlated to 'NEOPLASM.DISEASESTAGE' and 'NUMBER.OF.LYMPH.NODES'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 30 focal events and 15 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 12 significant findings detected.


		Clinical Features	Time to Death	AGE	NEOPLASM DISEASESTAGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	PATHOLOGY M STAGE	GENDER	HISTOLOGICAL TYPE	RADIATIONS RADIATION REGIMENINDICATION	RADIATIONEXPOSURE	EXTRATHYROIDAL EXTENSION	COMPLETENESS OF RESECTION	NUMBER OF LYMPH NODES	MULTIFOCALITY	TUMOR SIZE
	nCNV (%)	nWild-Type	logrank test	t-test	Chi-square 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	Fisher's exact test	Fisher's exact test	t-test	Fisher's exact test	t-test
del 11p15 1	7 (1%)	477	0.00126 (0.544)	0.000522 (0.228)	1.47e-07 (6.47e-05)	0.228 (1.00)	0.449 (1.00)	0.0964 (1.00)	0.0164 (1.00)	0.822 (1.00)	0.187 (1.00)	1 (1.00)	0.545 (1.00)	0.526 (1.00)	0.0813 (1.00)	0.709 (1.00)	0.0356 (1.00)
del xq22 3	4 (1%)	480	0.753 (1.00)	0.084 (1.00)	1.61e-06 (0.000708)	0.0583 (1.00)	0.123 (1.00)	0.107 (1.00)	0.0598 (1.00)	1 (1.00)	1 (1.00)	0.116 (1.00)	0.639 (1.00)	0.313 (1.00)	1.35e-25 (6.01e-23)	1 (1.00)	0.887 (1.00)
del 2p23 1	12 (2%)	472	0.694 (1.00)	0.677 (1.00)	0.015 (1.00)	0.892 (1.00)	0.0201 (1.00)	0.0247 (1.00)	0.529 (1.00)	0.00397 (1.00)	1 (1.00)	1 (1.00)	0.0824 (1.00)	0.536 (1.00)	2.7e-09 (1.19e-06)	1 (1.00)	0.859 (1.00)
del 2q35	12 (2%)	472	0.259 (1.00)	0.135 (1.00)	0.000707 (0.307)	0.647 (1.00)	0.00732 (1.00)	0.0247 (1.00)	0.529 (1.00)	0.0229 (1.00)	1 (1.00)	0.365 (1.00)	0.292 (1.00)	0.271 (1.00)	1.23e-25 (5.51e-23)	0.779 (1.00)	0.117 (1.00)
del 8p23 2	4 (1%)	480	0.872 (1.00)	0.981 (1.00)	0.189 (1.00)	1 (1.00)	0.248 (1.00)	0.374 (1.00)	0.0598 (1.00)	0.463 (1.00)	1 (1.00)	1 (1.00)	0.639 (1.00)	1 (1.00)	1.35e-25 (6.01e-23)	1 (1.00)	0.89 (1.00)
del 8p22	4 (1%)	480	0.872 (1.00)	0.981 (1.00)	0.189 (1.00)	1 (1.00)	0.248 (1.00)	0.374 (1.00)	0.0598 (1.00)	0.463 (1.00)	1 (1.00)	1 (1.00)	0.639 (1.00)	1 (1.00)	1.35e-25 (6.01e-23)	1 (1.00)	0.89 (1.00)
del 8p12	4 (1%)	480	0.872 (1.00)	0.981 (1.00)	0.189 (1.00)	1 (1.00)	0.248 (1.00)	0.374 (1.00)	0.0598 (1.00)	0.463 (1.00)	1 (1.00)	1 (1.00)	0.639 (1.00)	1 (1.00)	1.35e-25 (6.01e-23)	1 (1.00)	0.89 (1.00)
del 8q24 22	7 (1%)	477	0.843 (1.00)	0.39 (1.00)	0.104 (1.00)	0.79 (1.00)	0.0611 (1.00)	0.741 (1.00)	0.0164 (1.00)	0.154 (1.00)	1 (1.00)	1 (1.00)	0.753 (1.00)	0.526 (1.00)	1.32e-25 (5.89e-23)	1 (1.00)	0.342 (1.00)
del 9q21 13	22 (5%)	462	0.0288 (1.00)	0.0221 (1.00)	1.28e-09 (5.64e-07)	0.191 (1.00)	0.64 (1.00)	0.0151 (1.00)	0.324 (1.00)	0.711 (1.00)	0.483 (1.00)	0.585 (1.00)	0.0671 (1.00)	0.572 (1.00)	0.239 (1.00)	0.666 (1.00)	0.113 (1.00)
del 18q22 2	5 (1%)	479	0.708 (1.00)	0.27 (1.00)	0.312 (1.00)	0.187 (1.00)	0.623 (1.00)	0.689 (1.00)	1 (1.00)	0.569 (1.00)	1 (1.00)	1 (1.00)	0.442 (1.00)	1 (1.00)	7.2e-05 (0.0315)	0.38 (1.00)	0.305 (1.00)
amp xq22 3	15 (3%)	469	0.121 (1.00)	0.339 (1.00)	0.0101 (1.00)	0.566 (1.00)	0.416 (1.00)	0.699 (1.00)	0.0147 (1.00)	0.534 (1.00)	1 (1.00)	1 (1.00)	0.0132 (1.00)	0.791 (1.00)	0.948 (1.00)	0.303 (1.00)	0.668 (1.00)
del 1q24 2	3 (1%)	481	0.605 (1.00)	0.872 (1.00)	0.802 (1.00)	0.806 (1.00)	0.499 (1.00)	0.135 (1.00)	0.568 (1.00)	0.233 (1.00)	1 (1.00)	1 (1.00)	0.608 (1.00)	1 (1.00)		1 (1.00)	0.177 (1.00)
del 5p15 2	4 (1%)	480	0.894 (1.00)	0.243 (1.00)	0.739 (1.00)	0.629 (1.00)	0.372 (1.00)	0.197 (1.00)	0.578 (1.00)	0.0297 (1.00)	1 (1.00)	1 (1.00)	0.411 (1.00)	0.0694 (1.00)	0.184 (1.00)	0.34 (1.00)	0.278 (1.00)
del 6q22 31	7 (1%)	477	0.00817 (1.00)	0.123 (1.00)	0.365 (1.00)	0.79 (1.00)	0.372 (1.00)	0.0097 (1.00)	0.39 (1.00)	0.822 (1.00)	0.187 (1.00)	0.218 (1.00)	0.383 (1.00)	0.755 (1.00)	0.00208 (0.894)	0.459 (1.00)	0.0166 (1.00)
del 7q34	4 (1%)	480	0.747 (1.00)	0.82 (1.00)	0.793 (1.00)	0.554 (1.00)	0.623 (1.00)	1 (1.00)	1 (1.00)	0.124 (1.00)	1 (1.00)	1 (1.00)	0.639 (1.00)	1 (1.00)	0.231 (1.00)	0.628 (1.00)	0.189 (1.00)
del 10q21 2	12 (2%)	472	0.512 (1.00)	0.782 (1.00)	0.975 (1.00)	0.733 (1.00)	0.338 (1.00)	0.509 (1.00)	0.529 (1.00)	0.558 (1.00)	0.3 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.492 (1.00)	0.761 (1.00)	0.081 (1.00)
del 10q23 31	12 (2%)	472	0.508 (1.00)	0.123 (1.00)	0.0217 (1.00)	0.78 (1.00)	0.0201 (1.00)	0.0717 (1.00)	0.318 (1.00)	0.341 (1.00)	1 (1.00)	1 (1.00)	0.696 (1.00)	0.624 (1.00)	0.00131 (0.563)	1 (1.00)	0.00954 (1.00)
del 13q12 3	16 (3%)	468	0.625 (1.00)	0.00257 (1.00)	0.22 (1.00)	0.569 (1.00)	0.0875 (1.00)	0.129 (1.00)	0.148 (1.00)	0.53 (1.00)	0.379 (1.00)	0.00184 (0.791)	0.767 (1.00)	0.791 (1.00)	0.0629 (1.00)	0.803 (1.00)	0.308 (1.00)
del 13q21 31	18 (4%)	466	0.637 (1.00)	0.0753 (1.00)	0.886 (1.00)	0.782 (1.00)	0.0321 (1.00)	0.305 (1.00)	0.276 (1.00)	0.611 (1.00)	0.0913 (1.00)	0.00239 (1.00)	0.567 (1.00)	0.655 (1.00)	0.000607 (0.264)	0.475 (1.00)	0.498 (1.00)
del 15q25 3	9 (2%)	475	0.557 (1.00)	0.804 (1.00)	0.316 (1.00)	0.529 (1.00)	0.0678 (1.00)	0.0423 (1.00)	0.456 (1.00)	0.0907 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.251 (1.00)	1 (1.00)	0.195 (1.00)
del 16q23 3	6 (1%)	478	0.0862 (1.00)	0.03 (1.00)	0.000576 (0.251)	0.0148 (1.00)	0.449 (1.00)	0.14 (1.00)	1 (1.00)	0.17 (1.00)	1 (1.00)	0.218 (1.00)	0.0582 (1.00)	0.0721 (1.00)	0.46 (1.00)	1 (1.00)	0.469 (1.00)
del 17p13 1	7 (1%)	477	0.589 (1.00)	0.68 (1.00)	0.527 (1.00)	0.14 (1.00)	0.449 (1.00)	0.342 (1.00)	0.681 (1.00)	0.154 (1.00)	0.015 (1.00)	0.25 (1.00)	0.183 (1.00)	0.755 (1.00)	0.932 (1.00)	1 (1.00)	0.0926 (1.00)
del 18p11 21	4 (1%)	480	0.759 (1.00)	0.543 (1.00)	0.189 (1.00)	0.344 (1.00)	1 (1.00)	0.374 (1.00)	1 (1.00)	0.463 (1.00)	1 (1.00)	1 (1.00)	0.639 (1.00)	1 (1.00)	0.00208 (0.894)	0.628 (1.00)	0.233 (1.00)
del 19p13 2	7 (1%)	477	0.135 (1.00)	0.175 (1.00)	0.665 (1.00)	1 (1.00)	1 (1.00)	0.741 (1.00)	0.39 (1.00)	1 (1.00)	1 (1.00)	0.0281 (1.00)	1 (1.00)	0.19 (1.00)		0.459 (1.00)	0.00215 (0.919)
del 21q21 1	9 (2%)	475	0.839 (1.00)	0.0708 (1.00)	0.00838 (1.00)	0.267 (1.00)	1 (1.00)	0.592 (1.00)	0.706 (1.00)	0.661 (1.00)	1 (1.00)	1 (1.00)	0.611 (1.00)	0.396 (1.00)	0.899 (1.00)	0.314 (1.00)	0.655 (1.00)
del 22q13 1	84 (17%)	400	0.499 (1.00)	0.899 (1.00)	0.698 (1.00)	0.525 (1.00)	0.315 (1.00)	0.578 (1.00)	0.498 (1.00)	0.27 (1.00)	0.481 (1.00)	0.332 (1.00)	0.305 (1.00)	0.474 (1.00)	0.315 (1.00)	0.225 (1.00)	0.863 (1.00)
del 22q13 2	84 (17%)	400	0.499 (1.00)	0.899 (1.00)	0.698 (1.00)	0.525 (1.00)	0.315 (1.00)	0.578 (1.00)	0.498 (1.00)	0.27 (1.00)	0.481 (1.00)	0.332 (1.00)	0.305 (1.00)	0.474 (1.00)	0.315 (1.00)	0.225 (1.00)	0.863 (1.00)
del 22q13 31	84 (17%)	400	0.499 (1.00)	0.899 (1.00)	0.698 (1.00)	0.525 (1.00)	0.315 (1.00)	0.578 (1.00)	0.498 (1.00)	0.27 (1.00)	0.481 (1.00)	0.332 (1.00)	0.305 (1.00)	0.474 (1.00)	0.315 (1.00)	0.225 (1.00)	0.863 (1.00)
del 22q13 32	85 (18%)	399	0.497 (1.00)	0.942 (1.00)	0.699 (1.00)	0.512 (1.00)	0.261 (1.00)	0.6 (1.00)	0.589 (1.00)	0.193 (1.00)	0.481 (1.00)	0.218 (1.00)	0.271 (1.00)	0.474 (1.00)	0.275 (1.00)	0.184 (1.00)	0.863 (1.00)
del xq22 1	6 (1%)	478	0.729 (1.00)	0.209 (1.00)	0.000803 (0.348)	0.214 (1.00)	0.685 (1.00)	0.189 (1.00)	0.0459 (1.00)	1 (1.00)	1 (1.00)	0.185 (1.00)	0.353 (1.00)	0.317 (1.00)	0.811 (1.00)	0.422 (1.00)	0.473 (1.00)

'del_2p23.1' versus 'NUMBER.OF.LYMPH.NODES'

P value = 2.7e-09 (t-test), Q value = 1.2e-06

Table S1. Gene #3: 'del_2p23.1' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	385	3.6 (6.2)
DEL PEAK 2(2P23.1) MUTATED	10	0.3 (0.9)
DEL PEAK 2(2P23.1) WILD-TYPE	375	3.6 (6.3)

Figure S1. Get High-res Image Gene #3: 'del_2p23.1' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

'del_2q35' versus 'NUMBER.OF.LYMPH.NODES'

P value = 1.23e-25 (t-test), Q value = 5.5e-23

Table S2. Gene #4: 'del_2q35' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	385	3.6 (6.2)
DEL PEAK 3(2Q35) MUTATED	8	0.0 (0.0)
DEL PEAK 3(2Q35) WILD-TYPE	377	3.6 (6.2)

Figure S2. Get High-res Image Gene #4: 'del_2q35' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

'del_8p23.2' versus 'NUMBER.OF.LYMPH.NODES'

P value = 1.35e-25 (t-test), Q value = 6e-23

Table S3. Gene #8: 'del_8p23.2' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	385	3.6 (6.2)
DEL PEAK 9(8P23.2) MUTATED	4	0.0 (0.0)
DEL PEAK 9(8P23.2) WILD-TYPE	381	3.6 (6.2)

Figure S3. Get High-res Image Gene #8: 'del_8p23.2' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

'del_8p22' versus 'NUMBER.OF.LYMPH.NODES'

P value = 1.35e-25 (t-test), Q value = 6e-23

Table S4. Gene #9: 'del_8p22' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	385	3.6 (6.2)
DEL PEAK 10(8P22) MUTATED	4	0.0 (0.0)
DEL PEAK 10(8P22) WILD-TYPE	381	3.6 (6.2)

Figure S4. Get High-res Image Gene #9: 'del_8p22' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

'del_8p12' versus 'NUMBER.OF.LYMPH.NODES'

P value = 1.35e-25 (t-test), Q value = 6e-23

Table S5. Gene #10: 'del_8p12' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	385	3.6 (6.2)
DEL PEAK 11(8P12) MUTATED	4	0.0 (0.0)
DEL PEAK 11(8P12) WILD-TYPE	381	3.6 (6.2)

Figure S5. Get High-res Image Gene #10: 'del_8p12' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

'del_8q24.22' versus 'NUMBER.OF.LYMPH.NODES'

P value = 1.32e-25 (t-test), Q value = 5.9e-23

Table S6. Gene #11: 'del_8q24.22' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	385	3.6 (6.2)
DEL PEAK 12(8Q24.22) MUTATED	5	0.0 (0.0)
DEL PEAK 12(8Q24.22) WILD-TYPE	380	3.6 (6.2)

Figure S6. Get High-res Image Gene #11: 'del_8q24.22' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

'del_9q21.13' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.28e-09 (Chi-square test), Q value = 5.6e-07

Table S7. Gene #12: 'del_9q21.13' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV	STAGE IVA	STAGE IVC
ALL	274	50	106	2	44	6
DEL PEAK 13(9Q21.13) MUTATED	8	5	3	2	3	1
DEL PEAK 13(9Q21.13) WILD-TYPE	266	45	103	0	41	5

Figure S7. Get High-res Image Gene #12: 'del_9q21.13' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

'del_11p15.1' versus 'AGE'

P value = 0.000522 (t-test), Q value = 0.23

Table S8. Gene #15: 'del_11p15.1' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	484	47.1 (15.6)
DEL PEAK 16(11P15.1) MUTATED	7	68.1 (8.7)
DEL PEAK 16(11P15.1) WILD-TYPE	477	46.8 (15.4)

Figure S8. Get High-res Image Gene #15: 'del_11p15.1' versus Clinical Feature #2: 'AGE'

'del_11p15.1' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.47e-07 (Chi-square test), Q value = 6.5e-05

Table S9. Gene #15: 'del_11p15.1' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV	STAGE IVA	STAGE IVC
ALL	274	50	106	2	44	6
DEL PEAK 16(11P15.1) MUTATED	1	1	4	1	0	0
DEL PEAK 16(11P15.1) WILD-TYPE	273	49	102	1	44	6

Figure S9. Get High-res Image Gene #15: 'del_11p15.1' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

'del_18q22.2' versus 'NUMBER.OF.LYMPH.NODES'

P value = 7.2e-05 (t-test), Q value = 0.032

Table S10. Gene #22: 'del_18q22.2' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	385	3.6 (6.2)
DEL PEAK 24(18Q22.2) MUTATED	5	0.4 (0.9)
DEL PEAK 24(18Q22.2) WILD-TYPE	380	3.6 (6.2)

Figure S10. Get High-res Image Gene #22: 'del_18q22.2' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

'del_xq22.3' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.61e-06 (Chi-square test), Q value = 0.00071

Table S11. Gene #30: 'del_xq22.3' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IV	STAGE IVA	STAGE IVC
ALL	274	50	106	2	44	6
DEL PEAK 34(XQ22.3) MUTATED	0	4	0	0	0	0
DEL PEAK 34(XQ22.3) WILD-TYPE	274	46	106	2	44	6

Figure S11. Get High-res Image Gene #30: 'del_xq22.3' versus Clinical Feature #3: 'NEOPLASM.DISEASESTAGE'

'del_xq22.3' versus 'NUMBER.OF.LYMPH.NODES'

P value = 1.35e-25 (t-test), Q value = 6e-23

Table S12. Gene #30: 'del_xq22.3' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	385	3.6 (6.2)
DEL PEAK 34(XQ22.3) MUTATED	4	0.0 (0.0)
DEL PEAK 34(XQ22.3) WILD-TYPE	381	3.6 (6.2)

Figure S12. Get High-res Image Gene #30: 'del_xq22.3' versus Clinical Feature #13: 'NUMBER.OF.LYMPH.NODES'

Methods & Data

Input

Copy number data file = transformed.cor.cli.txt
Clinical data file = THCA-TP.merged_data.txt
Number of patients = 484
Number of significantly focal cnvs = 30
Number of selected clinical features = 15
Exclude genes that fewer than K tumors have mutations, K = 3

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene mutations were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R

Student's t-test analysis

For continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between tumors with and without gene mutations using 't.test' function in R

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.test' function in R

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.

Download Results

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References

[1] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)

[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)

[3] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)

[4] 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)

[5] 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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