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

Overview

Introduction

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

Summary

Testing the association between subtypes identified by 30 different clustering approaches and 8 clinical features across 493 patients, 26 significant findings detected with Q value < 0.25.

2 subtypes identified in current cancer cohort by 'Amp Peak 1(1q24.1) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Amp Peak 2(1q32.1) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Amp Peak 3(3q26.32) mutation analysis'. These subtypes correlate to 'PATHOLOGY.T', 'PATHOLOGICSPREAD(M)', and 'TUMOR.STAGE'.
2 subtypes identified in current cancer cohort by 'Amp Peak 4(4q32.1) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Amp Peak 5(5q35.1) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Amp Peak 6(7q36.3) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Amp Peak 7(8q24.22) mutation analysis'. These subtypes correlate to 'PATHOLOGY.T'.
2 subtypes identified in current cancer cohort by 'Amp Peak 8(10p14) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Amp Peak 9(17q24.3) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Amp Peak 10(Xp22.2) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Amp Peak 11(Xp11.4) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Amp Peak 12(Xq11.2) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 1(1p36.23) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 2(1p31.1) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 3(1q43) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 4(2q37.3) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 5(3p25.3) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 6(3p21.32) mutation analysis'. These subtypes correlate to 'PATHOLOGY.T' and 'TUMOR.STAGE'.
2 subtypes identified in current cancer cohort by 'Del Peak 7(3p12.2) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 8(3q11.2) mutation analysis'. These subtypes correlate to 'GENDER'.
2 subtypes identified in current cancer cohort by 'Del Peak 9(4q34.3) mutation analysis'. These subtypes correlate to 'Time to Death', 'PATHOLOGY.T', and 'TUMOR.STAGE'.
2 subtypes identified in current cancer cohort by 'Del Peak 10(6q26) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 11(6q26) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 12(8p23.2) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 13(9p23) mutation analysis'. These subtypes correlate to 'Time to Death', 'PATHOLOGY.T', 'PATHOLOGICSPREAD(M)', and 'TUMOR.STAGE'.
2 subtypes identified in current cancer cohort by 'Del Peak 14(9p21.3) mutation analysis'. These subtypes correlate to 'Time to Death', 'PATHOLOGY.T', 'PATHOLOGICSPREAD(M)', and 'TUMOR.STAGE'.
2 subtypes identified in current cancer cohort by 'Del Peak 15(10q23.31) mutation analysis'. These subtypes correlate to 'PATHOLOGY.T'.
2 subtypes identified in current cancer cohort by 'Del Peak 16(13q13.3) mutation analysis'. These subtypes correlate to 'Time to Death', 'PATHOLOGY.T', and 'TUMOR.STAGE'.
2 subtypes identified in current cancer cohort by 'Del Peak 17(14q31.1) mutation analysis'. These subtypes correlate to 'PATHOLOGY.T', 'PATHOLOGY.N', 'PATHOLOGICSPREAD(M)', and 'TUMOR.STAGE'.
2 subtypes identified in current cancer cohort by 'Del Peak 18(Xq23) mutation analysis'. These subtypes do not correlate to any clinical features.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between subtypes identified by 30 different clustering approaches and 8 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 26 significant findings detected.


Clinical Features	Time to Death	AGE	GENDER	KARNOFSKY PERFORMANCE SCORE	PATHOLOGY T	PATHOLOGY N	PATHOLOGICSPREAD(M)	TUMOR STAGE
Statistical Tests	logrank test	t-test	Fisher's exact test	t-test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test
Amp Peak 1(1q24 1)	0.2 (1.00)	0.164 (1.00)	0.666 (1.00)	0.499 (1.00)	0.157 (1.00)	0.0751 (1.00)	0.339 (1.00)	0.298 (1.00)
Amp Peak 2(1q32 1)	0.437 (1.00)	0.0725 (1.00)	0.771 (1.00)	0.499 (1.00)	0.164 (1.00)	0.482 (1.00)	0.703 (1.00)	0.24 (1.00)
Amp Peak 3(3q26 32)	0.156 (1.00)	0.903 (1.00)	0.442 (1.00)	0.152 (1.00)	0.000107 (0.0238)	0.0593 (1.00)	7.09e-05 (0.0159)	2.55e-05 (0.00579)
Amp Peak 4(4q32 1)	0.0584 (1.00)	0.416 (1.00)	0.258 (1.00)	0.411 (1.00)	0.265 (1.00)	0.574 (1.00)	0.462 (1.00)	0.415 (1.00)
Amp Peak 5(5q35 1)	0.0454 (1.00)	0.0923 (1.00)	0.141 (1.00)	0.944 (1.00)	0.295 (1.00)	0.31 (1.00)	0.366 (1.00)	0.629 (1.00)
Amp Peak 6(7q36 3)	0.724 (1.00)	0.806 (1.00)	0.0352 (1.00)	0.57 (1.00)	0.0563 (1.00)	0.443 (1.00)	0.00523 (1.00)	0.0202 (1.00)
Amp Peak 7(8q24 22)	0.0527 (1.00)	0.0214 (1.00)	0.11 (1.00)	0.297 (1.00)	0.00112 (0.237)	0.74 (1.00)	0.053 (1.00)	0.00241 (0.5)
Amp Peak 8(10p14)	0.234 (1.00)	0.423 (1.00)	0.594 (1.00)	0.887 (1.00)	0.013 (1.00)	0.188 (1.00)	0.288 (1.00)	0.0494 (1.00)
Amp Peak 9(17q24 3)	0.0512 (1.00)	0.0662 (1.00)	0.858 (1.00)	0.471 (1.00)	0.482 (1.00)	0.359 (1.00)	0.244 (1.00)	0.857 (1.00)
Amp Peak 10(Xp22 2)	0.468 (1.00)	0.676 (1.00)	0.854 (1.00)	0.726 (1.00)	0.0837 (1.00)	0.668 (1.00)	0.0897 (1.00)	0.0108 (1.00)
Amp Peak 11(Xp11 4)	0.759 (1.00)	0.712 (1.00)	0.857 (1.00)	0.726 (1.00)	0.0695 (1.00)	0.668 (1.00)	0.0509 (1.00)	0.00533 (1.00)
Amp Peak 12(Xq11 2)	0.803 (1.00)	0.145 (1.00)	0.706 (1.00)	0.726 (1.00)	0.179 (1.00)	0.647 (1.00)	0.31 (1.00)	0.0584 (1.00)
Del Peak 1(1p36 23)	0.0495 (1.00)	0.123 (1.00)	0.123 (1.00)	0.284 (1.00)	0.111 (1.00)	1 (1.00)	0.0844 (1.00)	0.168 (1.00)
Del Peak 2(1p31 1)	0.219 (1.00)	0.0726 (1.00)	0.016 (1.00)	0.284 (1.00)	0.0536 (1.00)	0.722 (1.00)	0.294 (1.00)	0.181 (1.00)
Del Peak 3(1q43)	0.704 (1.00)	0.335 (1.00)	1 (1.00)		0.0712 (1.00)	0.374 (1.00)	1 (1.00)	0.749 (1.00)
Del Peak 4(2q37 3)	0.673 (1.00)	0.63 (1.00)	0.153 (1.00)		0.822 (1.00)	1 (1.00)	0.402 (1.00)	0.556 (1.00)
Del Peak 5(3p25 3)	0.783 (1.00)	0.788 (1.00)	0.569 (1.00)	0.0817 (1.00)	0.00144 (0.303)	1 (1.00)	0.707 (1.00)	0.0129 (1.00)
Del Peak 6(3p21 32)	0.498 (1.00)	0.704 (1.00)	0.772 (1.00)	0.0817 (1.00)	3.34e-05 (0.00756)	1 (1.00)	0.333 (1.00)	0.00053 (0.115)
Del Peak 7(3p12 2)	0.614 (1.00)	0.761 (1.00)	0.00221 (0.461)	0.741 (1.00)	0.217 (1.00)	0.626 (1.00)	0.53 (1.00)	0.231 (1.00)
Del Peak 8(3q11 2)	0.635 (1.00)	0.0111 (1.00)	1.32e-07 (3.1e-05)	0.749 (1.00)	0.134 (1.00)	0.787 (1.00)	0.591 (1.00)	0.45 (1.00)
Del Peak 9(4q34 3)	0.000557 (0.12)	0.568 (1.00)	0.433 (1.00)	0.0261 (1.00)	4.27e-07 (9.98e-05)	1 (1.00)	0.00862 (1.00)	2.7e-06 (0.000626)
Del Peak 10(6q26)	0.565 (1.00)	0.287 (1.00)	0.012 (1.00)	0.256 (1.00)	0.621 (1.00)	0.0195 (1.00)	0.41 (1.00)	0.32 (1.00)
Del Peak 11(6q26)	0.589 (1.00)	0.226 (1.00)	0.00648 (1.00)	0.256 (1.00)	0.621 (1.00)	0.0195 (1.00)	0.41 (1.00)	0.32 (1.00)
Del Peak 12(8p23 2)	0.0385 (1.00)	0.139 (1.00)	0.256 (1.00)	0.893 (1.00)	0.176 (1.00)	0.786 (1.00)	0.055 (1.00)	0.14 (1.00)
Del Peak 13(9p23)	0.000138 (0.0304)	0.0136 (1.00)	0.00361 (0.744)	0.656 (1.00)	1.39e-05 (0.0032)	0.262 (1.00)	0.000876 (0.187)	5.62e-06 (0.0013)
Del Peak 14(9p21 3)	2.03e-06 (0.000473)	0.0261 (1.00)	0.00144 (0.303)	0.656 (1.00)	1.01e-07 (2.4e-05)	0.0589 (1.00)	6.93e-05 (0.0156)	3.39e-08 (8.03e-06)
Del Peak 15(10q23 31)	0.217 (1.00)	0.209 (1.00)	0.0272 (1.00)	0.764 (1.00)	0.000477 (0.104)	1 (1.00)	0.333 (1.00)	0.0177 (1.00)
Del Peak 16(13q13 3)	0.000848 (0.182)	0.884 (1.00)	0.794 (1.00)	0.748 (1.00)	1.48e-05 (0.0034)	0.325 (1.00)	0.0377 (1.00)	0.000348 (0.0762)
Del Peak 17(14q31 1)	0.00179 (0.374)	0.055 (1.00)	0.393 (1.00)	0.0872 (1.00)	0.000107 (0.0238)	0.000113 (0.0249)	0.00101 (0.216)	2.42e-05 (0.00553)
Del Peak 18(Xq23)	0.287 (1.00)	0.669 (1.00)	0.234 (1.00)		0.297 (1.00)	0.657 (1.00)	0.168 (1.00)	0.142 (1.00)

Clustering Approach #1: 'Amp Peak 1(1q24.1) mutation analysis'

Table S1. Description of clustering approach #1: 'Amp Peak 1(1q24.1) mutation analysis'

Cluster Labels	AMP PEAK 1(1Q24.1) MUTATED	AMP PEAK 1(1Q24.1) WILD-TYPE
Number of samples	60	433

Clustering Approach #2: 'Amp Peak 2(1q32.1) mutation analysis'

Table S2. Description of clustering approach #2: 'Amp Peak 2(1q32.1) mutation analysis'

Cluster Labels	AMP PEAK 2(1Q32.1) MUTATED	AMP PEAK 2(1Q32.1) WILD-TYPE
Number of samples	59	434

Clustering Approach #3: 'Amp Peak 3(3q26.32) mutation analysis'

Table S3. Description of clustering approach #3: 'Amp Peak 3(3q26.32) mutation analysis'

Cluster Labels	AMP PEAK 3(3Q26.32) MUTATED	AMP PEAK 3(3Q26.32) WILD-TYPE
Number of samples	80	413

'Amp Peak 3(3q26.32) mutation analysis' versus 'PATHOLOGY.T'

P value = 0.000107 (Fisher's exact test), Q value = 0.024

Table S4. Clustering Approach #3: 'Amp Peak 3(3q26.32) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

nPatients	T1	T2	T3	T4
ALL	242	64	176	11
AMP PEAK 3(3Q26.32) MUTATED	24	8	44	4
AMP PEAK 3(3Q26.32) WILD-TYPE	218	56	132	7

Figure S1. Get High-res Image Clustering Approach #3: 'Amp Peak 3(3q26.32) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

'Amp Peak 3(3q26.32) mutation analysis' versus 'PATHOLOGICSPREAD(M)'

P value = 7.09e-05 (Fisher's exact test), Q value = 0.016

Table S5. Clustering Approach #3: 'Amp Peak 3(3q26.32) mutation analysis' versus Clinical Feature #7: 'PATHOLOGICSPREAD(M)'

nPatients	M0	M1
ALL	417	76
AMP PEAK 3(3Q26.32) MUTATED	55	25
AMP PEAK 3(3Q26.32) WILD-TYPE	362	51

Figure S2. Get High-res Image Clustering Approach #3: 'Amp Peak 3(3q26.32) mutation analysis' versus Clinical Feature #7: 'PATHOLOGICSPREAD(M)'

'Amp Peak 3(3q26.32) mutation analysis' versus 'TUMOR.STAGE'

P value = 2.55e-05 (Fisher's exact test), Q value = 0.0058

Table S6. Clustering Approach #3: 'Amp Peak 3(3q26.32) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

nPatients	I	II	III	IV
ALL	238	52	123	80
AMP PEAK 3(3Q26.32) MUTATED	23	6	25	26
AMP PEAK 3(3Q26.32) WILD-TYPE	215	46	98	54

Figure S3. Get High-res Image Clustering Approach #3: 'Amp Peak 3(3q26.32) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

Clustering Approach #4: 'Amp Peak 4(4q32.1) mutation analysis'

Table S7. Description of clustering approach #4: 'Amp Peak 4(4q32.1) mutation analysis'

Cluster Labels	AMP PEAK 4(4Q32.1) MUTATED	AMP PEAK 4(4Q32.1) WILD-TYPE
Number of samples	14	479

Clustering Approach #5: 'Amp Peak 5(5q35.1) mutation analysis'

Table S8. Description of clustering approach #5: 'Amp Peak 5(5q35.1) mutation analysis'

Cluster Labels	AMP PEAK 5(5Q35.1) MUTATED	AMP PEAK 5(5Q35.1) WILD-TYPE
Number of samples	311	182

Clustering Approach #6: 'Amp Peak 6(7q36.3) mutation analysis'

Table S9. Description of clustering approach #6: 'Amp Peak 6(7q36.3) mutation analysis'

Cluster Labels	AMP PEAK 6(7Q36.3) MUTATED	AMP PEAK 6(7Q36.3) WILD-TYPE
Number of samples	163	330

Clustering Approach #7: 'Amp Peak 7(8q24.22) mutation analysis'

Table S10. Description of clustering approach #7: 'Amp Peak 7(8q24.22) mutation analysis'

Cluster Labels	AMP PEAK 7(8Q24.22) MUTATED	AMP PEAK 7(8Q24.22) WILD-TYPE
Number of samples	73	420

'Amp Peak 7(8q24.22) mutation analysis' versus 'PATHOLOGY.T'

P value = 0.00112 (Fisher's exact test), Q value = 0.24

Table S11. Clustering Approach #7: 'Amp Peak 7(8q24.22) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

nPatients	T1	T2	T3	T4
ALL	242	64	176	11
AMP PEAK 7(8Q24.22) MUTATED	21	11	39	2
AMP PEAK 7(8Q24.22) WILD-TYPE	221	53	137	9

Figure S4. Get High-res Image Clustering Approach #7: 'Amp Peak 7(8q24.22) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

Clustering Approach #8: 'Amp Peak 8(10p14) mutation analysis'

Table S12. Description of clustering approach #8: 'Amp Peak 8(10p14) mutation analysis'

Cluster Labels	AMP PEAK 8(10P14) MUTATED	AMP PEAK 8(10P14) WILD-TYPE
Number of samples	16	477

Clustering Approach #9: 'Amp Peak 9(17q24.3) mutation analysis'

Table S13. Description of clustering approach #9: 'Amp Peak 9(17q24.3) mutation analysis'

Cluster Labels	AMP PEAK 9(17Q24.3) MUTATED	AMP PEAK 9(17Q24.3) WILD-TYPE
Number of samples	37	456

Clustering Approach #10: 'Amp Peak 10(Xp22.2) mutation analysis'

Table S14. Description of clustering approach #10: 'Amp Peak 10(Xp22.2) mutation analysis'

Cluster Labels	AMP PEAK 10(XP22.2) MUTATED	AMP PEAK 10(XP22.2) WILD-TYPE
Number of samples	35	458

Clustering Approach #11: 'Amp Peak 11(Xp11.4) mutation analysis'

Table S15. Description of clustering approach #11: 'Amp Peak 11(Xp11.4) mutation analysis'

Cluster Labels	AMP PEAK 11(XP11.4) MUTATED	AMP PEAK 11(XP11.4) WILD-TYPE
Number of samples	36	457

Clustering Approach #12: 'Amp Peak 12(Xq11.2) mutation analysis'

Table S16. Description of clustering approach #12: 'Amp Peak 12(Xq11.2) mutation analysis'

Cluster Labels	AMP PEAK 12(XQ11.2) MUTATED	AMP PEAK 12(XQ11.2) WILD-TYPE
Number of samples	32	461

Clustering Approach #13: 'Del Peak 1(1p36.23) mutation analysis'

Table S17. Description of clustering approach #13: 'Del Peak 1(1p36.23) mutation analysis'

Cluster Labels	DEL PEAK 1(1P36.23) MUTATED	DEL PEAK 1(1P36.23) WILD-TYPE
Number of samples	98	395

Clustering Approach #14: 'Del Peak 2(1p31.1) mutation analysis'

Table S18. Description of clustering approach #14: 'Del Peak 2(1p31.1) mutation analysis'

Cluster Labels	DEL PEAK 2(1P31.1) MUTATED	DEL PEAK 2(1P31.1) WILD-TYPE
Number of samples	72	421

Clustering Approach #15: 'Del Peak 3(1q43) mutation analysis'

Table S19. Description of clustering approach #15: 'Del Peak 3(1q43) mutation analysis'

Cluster Labels	DEL PEAK 3(1Q43) MUTATED	DEL PEAK 3(1Q43) WILD-TYPE
Number of samples	38	455

Clustering Approach #16: 'Del Peak 4(2q37.3) mutation analysis'

Table S20. Description of clustering approach #16: 'Del Peak 4(2q37.3) mutation analysis'

Cluster Labels	DEL PEAK 4(2Q37.3) MUTATED	DEL PEAK 4(2Q37.3) WILD-TYPE
Number of samples	48	445

Clustering Approach #17: 'Del Peak 5(3p25.3) mutation analysis'

Table S21. Description of clustering approach #17: 'Del Peak 5(3p25.3) mutation analysis'

Cluster Labels	DEL PEAK 5(3P25.3) MUTATED	DEL PEAK 5(3P25.3) WILD-TYPE
Number of samples	432	61

Clustering Approach #18: 'Del Peak 6(3p21.32) mutation analysis'

Table S22. Description of clustering approach #18: 'Del Peak 6(3p21.32) mutation analysis'

Cluster Labels	DEL PEAK 6(3P21.32) MUTATED	DEL PEAK 6(3P21.32) WILD-TYPE
Number of samples	435	58

'Del Peak 6(3p21.32) mutation analysis' versus 'PATHOLOGY.T'

P value = 3.34e-05 (Fisher's exact test), Q value = 0.0076

Table S23. Clustering Approach #18: 'Del Peak 6(3p21.32) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

nPatients	T1	T2	T3	T4
ALL	242	64	176	11
DEL PEAK 6(3P21.32) MUTATED	209	52	168	6
DEL PEAK 6(3P21.32) WILD-TYPE	33	12	8	5

Figure S5. Get High-res Image Clustering Approach #18: 'Del Peak 6(3p21.32) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

'Del Peak 6(3p21.32) mutation analysis' versus 'TUMOR.STAGE'

P value = 0.00053 (Fisher's exact test), Q value = 0.12

Table S24. Clustering Approach #18: 'Del Peak 6(3p21.32) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

nPatients	I	II	III	IV
ALL	238	52	123	80
DEL PEAK 6(3P21.32) MUTATED	205	40	119	71
DEL PEAK 6(3P21.32) WILD-TYPE	33	12	4	9

Figure S6. Get High-res Image Clustering Approach #18: 'Del Peak 6(3p21.32) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

Clustering Approach #19: 'Del Peak 7(3p12.2) mutation analysis'

Table S25. Description of clustering approach #19: 'Del Peak 7(3p12.2) mutation analysis'

Cluster Labels	DEL PEAK 7(3P12.2) MUTATED	DEL PEAK 7(3P12.2) WILD-TYPE
Number of samples	283	210

Clustering Approach #20: 'Del Peak 8(3q11.2) mutation analysis'

Table S26. Description of clustering approach #20: 'Del Peak 8(3q11.2) mutation analysis'

Cluster Labels	DEL PEAK 8(3Q11.2) MUTATED	DEL PEAK 8(3Q11.2) WILD-TYPE
Number of samples	150	343

'Del Peak 8(3q11.2) mutation analysis' versus 'GENDER'

P value = 1.32e-07 (Fisher's exact test), Q value = 3.1e-05

Table S27. Clustering Approach #20: 'Del Peak 8(3q11.2) mutation analysis' versus Clinical Feature #3: 'GENDER'

nPatients	FEMALE	MALE
ALL	171	322
DEL PEAK 8(3Q11.2) MUTATED	27	123
DEL PEAK 8(3Q11.2) WILD-TYPE	144	199

Figure S7. Get High-res Image Clustering Approach #20: 'Del Peak 8(3q11.2) mutation analysis' versus Clinical Feature #3: 'GENDER'

Clustering Approach #21: 'Del Peak 9(4q34.3) mutation analysis'

Table S28. Description of clustering approach #21: 'Del Peak 9(4q34.3) mutation analysis'

Cluster Labels	DEL PEAK 9(4Q34.3) MUTATED	DEL PEAK 9(4Q34.3) WILD-TYPE
Number of samples	76	417

'Del Peak 9(4q34.3) mutation analysis' versus 'Time to Death'

P value = 0.000557 (logrank test), Q value = 0.12

Table S29. Clustering Approach #21: 'Del Peak 9(4q34.3) mutation analysis' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	490	158	0.1 - 111.0 (35.2)
DEL PEAK 9(4Q34.3) MUTATED	76	38	0.2 - 91.4 (35.1)
DEL PEAK 9(4Q34.3) WILD-TYPE	414	120	0.1 - 111.0 (35.2)

Figure S8. Get High-res Image Clustering Approach #21: 'Del Peak 9(4q34.3) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Del Peak 9(4q34.3) mutation analysis' versus 'PATHOLOGY.T'

P value = 4.27e-07 (Fisher's exact test), Q value = 1e-04

Table S30. Clustering Approach #21: 'Del Peak 9(4q34.3) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

nPatients	T1	T2	T3	T4
ALL	242	64	176	11
DEL PEAK 9(4Q34.3) MUTATED	19	8	43	6
DEL PEAK 9(4Q34.3) WILD-TYPE	223	56	133	5

Figure S9. Get High-res Image Clustering Approach #21: 'Del Peak 9(4q34.3) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

'Del Peak 9(4q34.3) mutation analysis' versus 'TUMOR.STAGE'

P value = 2.7e-06 (Fisher's exact test), Q value = 0.00063

Table S31. Clustering Approach #21: 'Del Peak 9(4q34.3) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

nPatients	I	II	III	IV
ALL	238	52	123	80
DEL PEAK 9(4Q34.3) MUTATED	18	6	30	22
DEL PEAK 9(4Q34.3) WILD-TYPE	220	46	93	58

Figure S10. Get High-res Image Clustering Approach #21: 'Del Peak 9(4q34.3) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

Clustering Approach #22: 'Del Peak 10(6q26) mutation analysis'

Table S32. Description of clustering approach #22: 'Del Peak 10(6q26) mutation analysis'

Cluster Labels	DEL PEAK 10(6Q26) MUTATED	DEL PEAK 10(6Q26) WILD-TYPE
Number of samples	142	351

Clustering Approach #23: 'Del Peak 11(6q26) mutation analysis'

Table S33. Description of clustering approach #23: 'Del Peak 11(6q26) mutation analysis'

Cluster Labels	DEL PEAK 11(6Q26) MUTATED	DEL PEAK 11(6Q26) WILD-TYPE
Number of samples	142	351

Clustering Approach #24: 'Del Peak 12(8p23.2) mutation analysis'

Table S34. Description of clustering approach #24: 'Del Peak 12(8p23.2) mutation analysis'

Cluster Labels	DEL PEAK 12(8P23.2) MUTATED	DEL PEAK 12(8P23.2) WILD-TYPE
Number of samples	146	347

Clustering Approach #25: 'Del Peak 13(9p23) mutation analysis'

Table S35. Description of clustering approach #25: 'Del Peak 13(9p23) mutation analysis'

Cluster Labels	DEL PEAK 13(9P23) MUTATED	DEL PEAK 13(9P23) WILD-TYPE
Number of samples	144	349

'Del Peak 13(9p23) mutation analysis' versus 'Time to Death'

P value = 0.000138 (logrank test), Q value = 0.03

Table S36. Clustering Approach #25: 'Del Peak 13(9p23) mutation analysis' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	490	158	0.1 - 111.0 (35.2)
DEL PEAK 13(9P23) MUTATED	143	65	0.2 - 109.9 (36.1)
DEL PEAK 13(9P23) WILD-TYPE	347	93	0.1 - 111.0 (34.6)

Figure S11. Get High-res Image Clustering Approach #25: 'Del Peak 13(9p23) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Del Peak 13(9p23) mutation analysis' versus 'PATHOLOGY.T'

P value = 1.39e-05 (Fisher's exact test), Q value = 0.0032

Table S37. Clustering Approach #25: 'Del Peak 13(9p23) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

nPatients	T1	T2	T3	T4
ALL	242	64	176	11
DEL PEAK 13(9P23) MUTATED	50	15	74	5
DEL PEAK 13(9P23) WILD-TYPE	192	49	102	6

Figure S12. Get High-res Image Clustering Approach #25: 'Del Peak 13(9p23) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

'Del Peak 13(9p23) mutation analysis' versus 'PATHOLOGICSPREAD(M)'

P value = 0.000876 (Fisher's exact test), Q value = 0.19

Table S38. Clustering Approach #25: 'Del Peak 13(9p23) mutation analysis' versus Clinical Feature #7: 'PATHOLOGICSPREAD(M)'

nPatients	M0	M1
ALL	417	76
DEL PEAK 13(9P23) MUTATED	109	35
DEL PEAK 13(9P23) WILD-TYPE	308	41

Figure S13. Get High-res Image Clustering Approach #25: 'Del Peak 13(9p23) mutation analysis' versus Clinical Feature #7: 'PATHOLOGICSPREAD(M)'

'Del Peak 13(9p23) mutation analysis' versus 'TUMOR.STAGE'

P value = 5.62e-06 (Fisher's exact test), Q value = 0.0013

Table S39. Clustering Approach #25: 'Del Peak 13(9p23) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

nPatients	I	II	III	IV
ALL	238	52	123	80
DEL PEAK 13(9P23) MUTATED	48	11	49	36
DEL PEAK 13(9P23) WILD-TYPE	190	41	74	44

Figure S14. Get High-res Image Clustering Approach #25: 'Del Peak 13(9p23) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

Clustering Approach #26: 'Del Peak 14(9p21.3) mutation analysis'

Table S40. Description of clustering approach #26: 'Del Peak 14(9p21.3) mutation analysis'

Cluster Labels	DEL PEAK 14(9P21.3) MUTATED	DEL PEAK 14(9P21.3) WILD-TYPE
Number of samples	152	341

'Del Peak 14(9p21.3) mutation analysis' versus 'Time to Death'

P value = 2.03e-06 (logrank test), Q value = 0.00047

Table S41. Clustering Approach #26: 'Del Peak 14(9p21.3) mutation analysis' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	490	158	0.1 - 111.0 (35.2)
DEL PEAK 14(9P21.3) MUTATED	152	72	0.2 - 109.9 (31.5)
DEL PEAK 14(9P21.3) WILD-TYPE	338	86	0.1 - 111.0 (36.2)

Figure S15. Get High-res Image Clustering Approach #26: 'Del Peak 14(9p21.3) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Del Peak 14(9p21.3) mutation analysis' versus 'PATHOLOGY.T'

P value = 1.01e-07 (Fisher's exact test), Q value = 2.4e-05

Table S42. Clustering Approach #26: 'Del Peak 14(9p21.3) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

nPatients	T1	T2	T3	T4
ALL	242	64	176	11
DEL PEAK 14(9P21.3) MUTATED	51	14	81	6
DEL PEAK 14(9P21.3) WILD-TYPE	191	50	95	5

Figure S16. Get High-res Image Clustering Approach #26: 'Del Peak 14(9p21.3) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

'Del Peak 14(9p21.3) mutation analysis' versus 'PATHOLOGICSPREAD(M)'

P value = 6.93e-05 (Fisher's exact test), Q value = 0.016

Table S43. Clustering Approach #26: 'Del Peak 14(9p21.3) mutation analysis' versus Clinical Feature #7: 'PATHOLOGICSPREAD(M)'

nPatients	M0	M1
ALL	417	76
DEL PEAK 14(9P21.3) MUTATED	113	39
DEL PEAK 14(9P21.3) WILD-TYPE	304	37

Figure S17. Get High-res Image Clustering Approach #26: 'Del Peak 14(9p21.3) mutation analysis' versus Clinical Feature #7: 'PATHOLOGICSPREAD(M)'

'Del Peak 14(9p21.3) mutation analysis' versus 'TUMOR.STAGE'

P value = 3.39e-08 (Fisher's exact test), Q value = 8e-06

Table S44. Clustering Approach #26: 'Del Peak 14(9p21.3) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

nPatients	I	II	III	IV
ALL	238	52	123	80
DEL PEAK 14(9P21.3) MUTATED	49	10	52	41
DEL PEAK 14(9P21.3) WILD-TYPE	189	42	71	39

Figure S18. Get High-res Image Clustering Approach #26: 'Del Peak 14(9p21.3) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

Clustering Approach #27: 'Del Peak 15(10q23.31) mutation analysis'

Table S45. Description of clustering approach #27: 'Del Peak 15(10q23.31) mutation analysis'

Cluster Labels	DEL PEAK 15(10Q23.31) MUTATED	DEL PEAK 15(10Q23.31) WILD-TYPE
Number of samples	90	403

'Del Peak 15(10q23.31) mutation analysis' versus 'PATHOLOGY.T'

P value = 0.000477 (Fisher's exact test), Q value = 0.1

Table S46. Clustering Approach #27: 'Del Peak 15(10q23.31) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

nPatients	T1	T2	T3	T4
ALL	242	64	176	11
DEL PEAK 15(10Q23.31) MUTATED	31	10	43	6
DEL PEAK 15(10Q23.31) WILD-TYPE	211	54	133	5

Figure S19. Get High-res Image Clustering Approach #27: 'Del Peak 15(10q23.31) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

Clustering Approach #28: 'Del Peak 16(13q13.3) mutation analysis'

Table S47. Description of clustering approach #28: 'Del Peak 16(13q13.3) mutation analysis'

Cluster Labels	DEL PEAK 16(13Q13.3) MUTATED	DEL PEAK 16(13Q13.3) WILD-TYPE
Number of samples	76	417

'Del Peak 16(13q13.3) mutation analysis' versus 'Time to Death'

P value = 0.000848 (logrank test), Q value = 0.18

Table S48. Clustering Approach #28: 'Del Peak 16(13q13.3) mutation analysis' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	490	158	0.1 - 111.0 (35.2)
DEL PEAK 16(13Q13.3) MUTATED	75	34	0.1 - 89.4 (28.5)
DEL PEAK 16(13Q13.3) WILD-TYPE	415	124	0.1 - 111.0 (36.3)

Figure S20. Get High-res Image Clustering Approach #28: 'Del Peak 16(13q13.3) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Del Peak 16(13q13.3) mutation analysis' versus 'PATHOLOGY.T'

P value = 1.48e-05 (Fisher's exact test), Q value = 0.0034

Table S49. Clustering Approach #28: 'Del Peak 16(13q13.3) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

nPatients	T1	T2	T3	T4
ALL	242	64	176	11
DEL PEAK 16(13Q13.3) MUTATED	28	3	39	6
DEL PEAK 16(13Q13.3) WILD-TYPE	214	61	137	5

Figure S21. Get High-res Image Clustering Approach #28: 'Del Peak 16(13q13.3) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

'Del Peak 16(13q13.3) mutation analysis' versus 'TUMOR.STAGE'

P value = 0.000348 (Fisher's exact test), Q value = 0.076

Table S50. Clustering Approach #28: 'Del Peak 16(13q13.3) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

nPatients	I	II	III	IV
ALL	238	52	123	80
DEL PEAK 16(13Q13.3) MUTATED	27	2	27	20
DEL PEAK 16(13Q13.3) WILD-TYPE	211	50	96	60

Figure S22. Get High-res Image Clustering Approach #28: 'Del Peak 16(13q13.3) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

Clustering Approach #29: 'Del Peak 17(14q31.1) mutation analysis'

Table S51. Description of clustering approach #29: 'Del Peak 17(14q31.1) mutation analysis'

Cluster Labels	DEL PEAK 17(14Q31.1) MUTATED	DEL PEAK 17(14Q31.1) WILD-TYPE
Number of samples	218	275

'Del Peak 17(14q31.1) mutation analysis' versus 'PATHOLOGY.T'

P value = 0.000107 (Fisher's exact test), Q value = 0.024

Table S52. Clustering Approach #29: 'Del Peak 17(14q31.1) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

nPatients	T1	T2	T3	T4
ALL	242	64	176	11
DEL PEAK 17(14Q31.1) MUTATED	83	35	96	4
DEL PEAK 17(14Q31.1) WILD-TYPE	159	29	80	7

Figure S23. Get High-res Image Clustering Approach #29: 'Del Peak 17(14q31.1) mutation analysis' versus Clinical Feature #5: 'PATHOLOGY.T'

'Del Peak 17(14q31.1) mutation analysis' versus 'PATHOLOGY.N'

P value = 0.000113 (Fisher's exact test), Q value = 0.025

Table S53. Clustering Approach #29: 'Del Peak 17(14q31.1) mutation analysis' versus Clinical Feature #6: 'PATHOLOGY.N'

nPatients	0	1
ALL	228	18
DEL PEAK 17(14Q31.1) MUTATED	96	16
DEL PEAK 17(14Q31.1) WILD-TYPE	132	2

Figure S24. Get High-res Image Clustering Approach #29: 'Del Peak 17(14q31.1) mutation analysis' versus Clinical Feature #6: 'PATHOLOGY.N'

'Del Peak 17(14q31.1) mutation analysis' versus 'PATHOLOGICSPREAD(M)'

P value = 0.00101 (Fisher's exact test), Q value = 0.22

Table S54. Clustering Approach #29: 'Del Peak 17(14q31.1) mutation analysis' versus Clinical Feature #7: 'PATHOLOGICSPREAD(M)'

nPatients	M0	M1
ALL	417	76
DEL PEAK 17(14Q31.1) MUTATED	171	47
DEL PEAK 17(14Q31.1) WILD-TYPE	246	29

Figure S25. Get High-res Image Clustering Approach #29: 'Del Peak 17(14q31.1) mutation analysis' versus Clinical Feature #7: 'PATHOLOGICSPREAD(M)'

'Del Peak 17(14q31.1) mutation analysis' versus 'TUMOR.STAGE'

P value = 2.42e-05 (Fisher's exact test), Q value = 0.0055

Table S55. Clustering Approach #29: 'Del Peak 17(14q31.1) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

nPatients	I	II	III	IV
ALL	238	52	123	80
DEL PEAK 17(14Q31.1) MUTATED	79	25	68	46
DEL PEAK 17(14Q31.1) WILD-TYPE	159	27	55	34

Figure S26. Get High-res Image Clustering Approach #29: 'Del Peak 17(14q31.1) mutation analysis' versus Clinical Feature #8: 'TUMOR.STAGE'

Clustering Approach #30: 'Del Peak 18(Xq23) mutation analysis'

Table S56. Description of clustering approach #30: 'Del Peak 18(Xq23) mutation analysis'

Cluster Labels	DEL PEAK 18(XQ23) MUTATED	DEL PEAK 18(XQ23) WILD-TYPE
Number of samples	55	438

Methods & Data

Input

Cluster data file = all_lesions.conf_99.cnv.cluster.txt
Clinical data file = KIRC-TP.clin.merged.picked.txt
Number of patients = 493
Number of clustering approaches = 30
Number of selected clinical features = 8
Exclude small clusters that include fewer than K patients, 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 two tumor subtypes using 't.test' function in R

Fisher's exact test

For binary clinical features, 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] 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] 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)

[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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