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 24 different clustering approaches and 15 clinical features across 284 patients, 15 significant findings detected with Q value < 0.25.

2 subtypes identified in current cancer cohort by 'Del Peak 2(2p22.3) mutation analysis'. These subtypes correlate to 'NUMBER.OF.LYMPH.NODES'.
2 subtypes identified in current cancer cohort by 'Del Peak 3(2q35) mutation analysis'. These subtypes correlate to 'HISTOLOGICAL.TYPE', 'NUMBER.OF.LYMPH.NODES', and 'NEOPLASM.DISEASESTAGE'.
2 subtypes identified in current cancer cohort by 'Del Peak 5(6q22.31) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 6(6q27) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 8(7q34) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 10(8q24.22) mutation analysis'. These subtypes correlate to 'NUMBER.OF.LYMPH.NODES'.
2 subtypes identified in current cancer cohort by 'Del Peak 11(9p21.3) mutation analysis'. These subtypes correlate to 'NEOPLASM.DISEASESTAGE'.
2 subtypes identified in current cancer cohort by 'Del Peak 12(9q22.32) mutation analysis'. These subtypes correlate to 'NEOPLASM.DISEASESTAGE'.
2 subtypes identified in current cancer cohort by 'Del Peak 13(10q21.2) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 14(10q23.31) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 15(11p15.1) mutation analysis'. These subtypes correlate to 'NUMBER.OF.LYMPH.NODES'.
2 subtypes identified in current cancer cohort by 'Del Peak 16(13q12.3) mutation analysis'. These subtypes correlate to 'RADIATIONEXPOSURE'.
2 subtypes identified in current cancer cohort by 'Del Peak 17(13q14.3) mutation analysis'. These subtypes correlate to 'RADIATIONEXPOSURE'.
2 subtypes identified in current cancer cohort by 'Del Peak 18(15q25.3) mutation analysis'. These subtypes correlate to 'NUMBER.OF.LYMPH.NODES'.
2 subtypes identified in current cancer cohort by 'Del Peak 20(16q23.3) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 21(17p13.1) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 22(18p11.21) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 23(19p13.2) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 26(21q21.1) mutation analysis'. These subtypes correlate to 'NEOPLASM.DISEASESTAGE'.
2 subtypes identified in current cancer cohort by 'Del Peak 27(22q13.31) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 28(22q13.2) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 29(22q13.32) mutation analysis'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'Del Peak 30(Xq22.1) mutation analysis'. These subtypes correlate to 'NEOPLASM.DISEASESTAGE'.
2 subtypes identified in current cancer cohort by 'Del Peak 31(Xq22.3) mutation analysis'. These subtypes correlate to 'NUMBER.OF.LYMPH.NODES' and 'NEOPLASM.DISEASESTAGE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between subtypes identified by 24 different clustering approaches and 15 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 15 significant findings detected.


Clinical Features	Time to Death	AGE	GENDER	HISTOLOGICAL TYPE	RADIATIONS RADIATION REGIMENINDICATION	RADIATIONEXPOSURE	DISTANT METASTASIS	EXTRATHYROIDAL EXTENSION	LYMPH NODE METASTASIS	COMPLETENESS OF RESECTION	NUMBER OF LYMPH NODES	TUMOR STAGECODE	NEOPLASM DISEASESTAGE	MULTIFOCALITY	TUMOR SIZE
Statistical Tests	logrank test	t-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	Chi-square test	Fisher's exact test	t-test	t-test	Chi-square test	Fisher's exact test	t-test
Del Peak 2(2p22 3)	1 (1.00)	0.157 (1.00)	0.455 (1.00)	0.019 (1.00)	1 (1.00)	1 (1.00)	0.391 (1.00)	0.258 (1.00)	0.135 (1.00)	0.788 (1.00)	2.86e-14 (9.52e-12)		0.00102 (0.325)	0.749 (1.00)	0.688 (1.00)
Del Peak 3(2q35)	1 (1.00)	0.0123 (1.00)	0.684 (1.00)	0.000323 (0.104)	1 (1.00)	1 (1.00)	0.382 (1.00)	0.729 (1.00)	0.182 (1.00)	0.25 (1.00)	2.91e-14 (9.67e-12)		0.00014 (0.0453)	1 (1.00)	0.185 (1.00)
Del Peak 5(6q22 31)	0.00468 (1.00)	0.197 (1.00)	1 (1.00)	0.802 (1.00)	0.184 (1.00)	1 (1.00)	0.18 (1.00)	0.606 (1.00)	0.769 (1.00)	1 (1.00)	0.00663 (1.00)		0.0718 (1.00)	0.37 (1.00)	0.033 (1.00)
Del Peak 6(6q27)	0.00468 (1.00)	0.197 (1.00)	1 (1.00)	0.802 (1.00)	0.184 (1.00)	1 (1.00)	0.18 (1.00)	0.606 (1.00)	0.769 (1.00)	1 (1.00)	0.00663 (1.00)		0.0718 (1.00)	0.37 (1.00)	0.033 (1.00)
Del Peak 8(7q34)	1 (1.00)	0.759 (1.00)	1 (1.00)	0.251 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.606 (1.00)	0.769 (1.00)	1 (1.00)	0.374 (1.00)		0.7 (1.00)	0.37 (1.00)	0.23 (1.00)
Del Peak 10(8q24 22)	1 (1.00)	0.0567 (1.00)	0.109 (1.00)	0.0294 (1.00)	1 (1.00)	1 (1.00)	0.682 (1.00)	1 (1.00)	0.464 (1.00)	0.575 (1.00)	3.08e-14 (1.01e-11)		0.00506 (1.00)	0.684 (1.00)	0.185 (1.00)
Del Peak 11(9p21 3)	1 (1.00)	0.0401 (1.00)	0.682 (1.00)	0.627 (1.00)	1 (1.00)	1 (1.00)	0.519 (1.00)	0.3 (1.00)	0.309 (1.00)	0.309 (1.00)	0.00238 (0.755)		1.88e-05 (0.00612)	0.282 (1.00)	0.124 (1.00)
Del Peak 12(9q22 32)	1 (1.00)	0.124 (1.00)	1 (1.00)	0.239 (1.00)	0.402 (1.00)	0.34 (1.00)	0.302 (1.00)	0.553 (1.00)	0.101 (1.00)	0.822 (1.00)	0.373 (1.00)		8.59e-05 (0.0279)	1 (1.00)	0.833 (1.00)
Del Peak 13(10q21 2)	1 (1.00)	0.565 (1.00)	1 (1.00)	0.0672 (1.00)	0.301 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.585 (1.00)	0.699 (1.00)	0.293 (1.00)		0.618 (1.00)	1 (1.00)	0.0236 (1.00)
Del Peak 14(10q23 31)	1 (1.00)	0.0207 (1.00)	0.428 (1.00)	0.0242 (1.00)	1 (1.00)	1 (1.00)	0.765 (1.00)	0.729 (1.00)	0.219 (1.00)	1 (1.00)	0.0584 (1.00)		0.0117 (1.00)	0.723 (1.00)	0.0374 (1.00)
Del Peak 15(11p15 1)	0.00468 (1.00)	0.031 (1.00)	0.273 (1.00)	0.145 (1.00)	0.184 (1.00)	1 (1.00)	0.18 (1.00)	0.606 (1.00)	0.36 (1.00)	0.494 (1.00)	3.02e-14 (1e-11)		0.515 (1.00)	0.622 (1.00)	0.238 (1.00)
Del Peak 16(13q12 3)	0.00468 (1.00)	0.0131 (1.00)	0.131 (1.00)	0.108 (1.00)	0.402 (1.00)	0.000241 (0.0777)	0.302 (1.00)	0.553 (1.00)	0.277 (1.00)	0.488 (1.00)	0.0311 (1.00)		0.118 (1.00)	0.749 (1.00)	0.137 (1.00)
Del Peak 17(13q14 3)	0.00468 (1.00)	0.177 (1.00)	0.33 (1.00)	0.162 (1.00)	0.129 (1.00)	0.000601 (0.192)	0.441 (1.00)	0.446 (1.00)	0.0996 (1.00)	1 (1.00)	0.0358 (1.00)		0.535 (1.00)	0.377 (1.00)	0.353 (1.00)
Del Peak 18(15q25 3)	1 (1.00)	0.247 (1.00)	0.575 (1.00)	0.145 (1.00)	1 (1.00)	1 (1.00)	0.18 (1.00)	1 (1.00)	0.36 (1.00)	0.494 (1.00)	3.02e-14 (1e-11)		0.0489 (1.00)	0.622 (1.00)	0.626 (1.00)
Del Peak 20(16q23 3)	1 (1.00)	0.323 (1.00)	0.572 (1.00)	0.0221 (1.00)	1 (1.00)	0.128 (1.00)	1 (1.00)	0.192 (1.00)	0.708 (1.00)	0.4 (1.00)	0.0561 (1.00)		0.139 (1.00)	1 (1.00)
Del Peak 21(17p13 1)	1 (1.00)	0.944 (1.00)	0.333 (1.00)	0.367 (1.00)	0.0208 (1.00)	1 (1.00)	0.429 (1.00)	0.102 (1.00)	0.215 (1.00)	1 (1.00)	0.293 (1.00)		0.211 (1.00)	0.214 (1.00)	0.306 (1.00)
Del Peak 22(18p11 21)	1 (1.00)	0.958 (1.00)	0.572 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.865 (1.00)	1 (1.00)	0.0561 (1.00)		0.0502 (1.00)	0.622 (1.00)	0.976 (1.00)
Del Peak 23(19p13 2)	1 (1.00)	0.0248 (1.00)	1 (1.00)	0.145 (1.00)	1 (1.00)	1 (1.00)	0.604 (1.00)	1 (1.00)	0.105 (1.00)	0.4 (1.00)			0.722 (1.00)	0.37 (1.00)
Del Peak 26(21q21 1)	1 (1.00)	0.0042 (1.00)	1 (1.00)	0.447 (1.00)	1 (1.00)	1 (1.00)	0.519 (1.00)	1 (1.00)	0.334 (1.00)	0.201 (1.00)	0.946 (1.00)		0.000339 (0.109)	1 (1.00)	0.73 (1.00)
Del Peak 27(22q13 31)	0.724 (1.00)	0.748 (1.00)	0.719 (1.00)	0.0552 (1.00)	0.477 (1.00)	0.695 (1.00)	0.63 (1.00)	0.509 (1.00)	0.644 (1.00)	0.4 (1.00)	0.684 (1.00)		0.854 (1.00)	0.109 (1.00)	0.305 (1.00)
Del Peak 28(22q13 2)	0.724 (1.00)	0.748 (1.00)	0.719 (1.00)	0.0552 (1.00)	0.477 (1.00)	0.695 (1.00)	0.63 (1.00)	0.509 (1.00)	0.644 (1.00)	0.4 (1.00)	0.684 (1.00)		0.854 (1.00)	0.109 (1.00)	0.305 (1.00)
Del Peak 29(22q13 32)	0.724 (1.00)	0.798 (1.00)	0.595 (1.00)	0.0314 (1.00)	0.476 (1.00)	0.695 (1.00)	0.722 (1.00)	0.509 (1.00)	0.587 (1.00)	0.4 (1.00)	0.607 (1.00)		0.882 (1.00)	0.0799 (1.00)	0.305 (1.00)
Del Peak 30(Xq22 1)	1 (1.00)	0.177 (1.00)	0.0397 (1.00)	0.135 (1.00)	1 (1.00)	0.204 (1.00)	0.295 (1.00)	0.411 (1.00)	0.382 (1.00)	0.246 (1.00)	0.691 (1.00)		0.000772 (0.246)	0.684 (1.00)	0.682 (1.00)
Del Peak 31(Xq22 3)	1 (1.00)	0.0642 (1.00)	0.0536 (1.00)	0.206 (1.00)	1 (1.00)	0.128 (1.00)	0.18 (1.00)	0.606 (1.00)	0.36 (1.00)	0.494 (1.00)	3.02e-14 (1e-11)		2.08e-06 (0.000679)	1 (1.00)	0.515 (1.00)

Clustering Approach #1: 'Del Peak 2(2p22.3) mutation analysis'

Table S1. Description of clustering approach #1: 'Del Peak 2(2p22.3) mutation analysis'

Cluster Labels	DEL PEAK 2(2P22.3) MUTATED	DEL PEAK 2(2P22.3) WILD-TYPE
Number of samples	9	275

'Del Peak 2(2p22.3) mutation analysis' versus 'NUMBER.OF.LYMPH.NODES'

P value = 2.86e-14 (t-test), Q value = 9.5e-12

Table S2. Clustering Approach #1: 'Del Peak 2(2p22.3) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	225	2.8 (5.2)
DEL PEAK 2(2P22.3) MUTATED	7	0.0 (0.0)
DEL PEAK 2(2P22.3) WILD-TYPE	218	2.9 (5.3)

Figure S1. Get High-res Image Clustering Approach #1: 'Del Peak 2(2p22.3) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

Clustering Approach #2: 'Del Peak 3(2q35) mutation analysis'

Table S3. Description of clustering approach #2: 'Del Peak 3(2q35) mutation analysis'

Cluster Labels	DEL PEAK 3(2Q35) MUTATED	DEL PEAK 3(2Q35) WILD-TYPE
Number of samples	8	276

'Del Peak 3(2q35) mutation analysis' versus 'HISTOLOGICAL.TYPE'

P value = 0.000323 (Fisher's exact test), Q value = 0.1

Table S4. Clustering Approach #2: 'Del Peak 3(2q35) mutation analysis' versus Clinical Feature #4: 'HISTOLOGICAL.TYPE'

nPatients	OTHER	THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL	THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED)	THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES)
ALL	18	167	69	30
DEL PEAK 3(2Q35) MUTATED	4	1	3	0
DEL PEAK 3(2Q35) WILD-TYPE	14	166	66	30

Figure S2. Get High-res Image Clustering Approach #2: 'Del Peak 3(2q35) mutation analysis' versus Clinical Feature #4: 'HISTOLOGICAL.TYPE'

'Del Peak 3(2q35) mutation analysis' versus 'NUMBER.OF.LYMPH.NODES'

P value = 2.91e-14 (t-test), Q value = 9.7e-12

Table S5. Clustering Approach #2: 'Del Peak 3(2q35) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	225	2.8 (5.2)
DEL PEAK 3(2Q35) MUTATED	6	0.0 (0.0)
DEL PEAK 3(2Q35) WILD-TYPE	219	2.9 (5.3)

Figure S3. Get High-res Image Clustering Approach #2: 'Del Peak 3(2q35) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

'Del Peak 3(2q35) mutation analysis' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.00014 (Chi-square test), Q value = 0.045

Table S6. Clustering Approach #2: 'Del Peak 3(2q35) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IVA	STAGE IVC
ALL	161	32	62	25	3
DEL PEAK 3(2Q35) MUTATED	1	5	2	0	0
DEL PEAK 3(2Q35) WILD-TYPE	160	27	60	25	3

Figure S4. Get High-res Image Clustering Approach #2: 'Del Peak 3(2q35) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #3: 'Del Peak 5(6q22.31) mutation analysis'

Table S7. Description of clustering approach #3: 'Del Peak 5(6q22.31) mutation analysis'

Cluster Labels	DEL PEAK 5(6Q22.31) MUTATED	DEL PEAK 5(6Q22.31) WILD-TYPE
Number of samples	4	280

Clustering Approach #4: 'Del Peak 6(6q27) mutation analysis'

Table S8. Description of clustering approach #4: 'Del Peak 6(6q27) mutation analysis'

Cluster Labels	DEL PEAK 6(6Q27) MUTATED	DEL PEAK 6(6Q27) WILD-TYPE
Number of samples	4	280

Clustering Approach #5: 'Del Peak 8(7q34) mutation analysis'

Table S9. Description of clustering approach #5: 'Del Peak 8(7q34) mutation analysis'

Cluster Labels	DEL PEAK 8(7Q34) MUTATED	DEL PEAK 8(7Q34) WILD-TYPE
Number of samples	4	280

Clustering Approach #6: 'Del Peak 10(8q24.22) mutation analysis'

Table S10. Description of clustering approach #6: 'Del Peak 10(8q24.22) mutation analysis'

Cluster Labels	DEL PEAK 10(8Q24.22) MUTATED	DEL PEAK 10(8Q24.22) WILD-TYPE
Number of samples	5	279

'Del Peak 10(8q24.22) mutation analysis' versus 'NUMBER.OF.LYMPH.NODES'

P value = 3.08e-14 (t-test), Q value = 1e-11

Table S11. Clustering Approach #6: 'Del Peak 10(8q24.22) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	225	2.8 (5.2)
DEL PEAK 10(8Q24.22) MUTATED	3	0.0 (0.0)
DEL PEAK 10(8Q24.22) WILD-TYPE	222	2.9 (5.3)

Figure S5. Get High-res Image Clustering Approach #6: 'Del Peak 10(8q24.22) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

Clustering Approach #7: 'Del Peak 11(9p21.3) mutation analysis'

Table S12. Description of clustering approach #7: 'Del Peak 11(9p21.3) mutation analysis'

Cluster Labels	DEL PEAK 11(9P21.3) MUTATED	DEL PEAK 11(9P21.3) WILD-TYPE
Number of samples	7	277

'Del Peak 11(9p21.3) mutation analysis' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.88e-05 (Chi-square test), Q value = 0.0061

Table S13. Clustering Approach #7: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IVA	STAGE IVC
ALL	161	32	62	25	3
DEL PEAK 11(9P21.3) MUTATED	1	5	0	1	0
DEL PEAK 11(9P21.3) WILD-TYPE	160	27	62	24	3

Figure S6. Get High-res Image Clustering Approach #7: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #8: 'Del Peak 12(9q22.32) mutation analysis'

Table S14. Description of clustering approach #8: 'Del Peak 12(9q22.32) mutation analysis'

Cluster Labels	DEL PEAK 12(9Q22.32) MUTATED	DEL PEAK 12(9Q22.32) WILD-TYPE
Number of samples	10	274

'Del Peak 12(9q22.32) mutation analysis' versus 'NEOPLASM.DISEASESTAGE'

P value = 8.59e-05 (Chi-square test), Q value = 0.028

Table S15. Clustering Approach #8: 'Del Peak 12(9q22.32) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IVA	STAGE IVC
ALL	161	32	62	25	3
DEL PEAK 12(9Q22.32) MUTATED	2	5	0	3	0
DEL PEAK 12(9Q22.32) WILD-TYPE	159	27	62	22	3

Figure S7. Get High-res Image Clustering Approach #8: 'Del Peak 12(9q22.32) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #9: 'Del Peak 13(10q21.2) mutation analysis'

Table S16. Description of clustering approach #9: 'Del Peak 13(10q21.2) mutation analysis'

Cluster Labels	DEL PEAK 13(10Q21.2) MUTATED	DEL PEAK 13(10Q21.2) WILD-TYPE
Number of samples	7	277

Clustering Approach #10: 'Del Peak 14(10q23.31) mutation analysis'

Table S17. Description of clustering approach #10: 'Del Peak 14(10q23.31) mutation analysis'

Cluster Labels	DEL PEAK 14(10Q23.31) MUTATED	DEL PEAK 14(10Q23.31) WILD-TYPE
Number of samples	8	276

Clustering Approach #11: 'Del Peak 15(11p15.1) mutation analysis'

Table S18. Description of clustering approach #11: 'Del Peak 15(11p15.1) mutation analysis'

Cluster Labels	DEL PEAK 15(11P15.1) MUTATED	DEL PEAK 15(11P15.1) WILD-TYPE
Number of samples	4	280

'Del Peak 15(11p15.1) mutation analysis' versus 'NUMBER.OF.LYMPH.NODES'

P value = 3.02e-14 (t-test), Q value = 1e-11

Table S19. Clustering Approach #11: 'Del Peak 15(11p15.1) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	225	2.8 (5.2)
DEL PEAK 15(11P15.1) MUTATED	4	0.0 (0.0)
DEL PEAK 15(11P15.1) WILD-TYPE	221	2.9 (5.3)

Figure S8. Get High-res Image Clustering Approach #11: 'Del Peak 15(11p15.1) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

Clustering Approach #12: 'Del Peak 16(13q12.3) mutation analysis'

Table S20. Description of clustering approach #12: 'Del Peak 16(13q12.3) mutation analysis'

Cluster Labels	DEL PEAK 16(13Q12.3) MUTATED	DEL PEAK 16(13Q12.3) WILD-TYPE
Number of samples	10	274

'Del Peak 16(13q12.3) mutation analysis' versus 'RADIATIONEXPOSURE'

P value = 0.000241 (Fisher's exact test), Q value = 0.078

Table S21. Clustering Approach #12: 'Del Peak 16(13q12.3) mutation analysis' versus Clinical Feature #6: 'RADIATIONEXPOSURE'

nPatients	NO	YES
ALL	237	11
DEL PEAK 16(13Q12.3) MUTATED	5	4
DEL PEAK 16(13Q12.3) WILD-TYPE	232	7

Figure S9. Get High-res Image Clustering Approach #12: 'Del Peak 16(13q12.3) mutation analysis' versus Clinical Feature #6: 'RADIATIONEXPOSURE'

Clustering Approach #13: 'Del Peak 17(13q14.3) mutation analysis'

Table S22. Description of clustering approach #13: 'Del Peak 17(13q14.3) mutation analysis'

Cluster Labels	DEL PEAK 17(13Q14.3) MUTATED	DEL PEAK 17(13Q14.3) WILD-TYPE
Number of samples	13	271

'Del Peak 17(13q14.3) mutation analysis' versus 'RADIATIONEXPOSURE'

P value = 0.000601 (Fisher's exact test), Q value = 0.19

Table S23. Clustering Approach #13: 'Del Peak 17(13q14.3) mutation analysis' versus Clinical Feature #6: 'RADIATIONEXPOSURE'

nPatients	NO	YES
ALL	237	11
DEL PEAK 17(13Q14.3) MUTATED	7	4
DEL PEAK 17(13Q14.3) WILD-TYPE	230	7

Figure S10. Get High-res Image Clustering Approach #13: 'Del Peak 17(13q14.3) mutation analysis' versus Clinical Feature #6: 'RADIATIONEXPOSURE'

Clustering Approach #14: 'Del Peak 18(15q25.3) mutation analysis'

Table S24. Description of clustering approach #14: 'Del Peak 18(15q25.3) mutation analysis'

Cluster Labels	DEL PEAK 18(15Q25.3) MUTATED	DEL PEAK 18(15Q25.3) WILD-TYPE
Number of samples	4	280

'Del Peak 18(15q25.3) mutation analysis' versus 'NUMBER.OF.LYMPH.NODES'

P value = 3.02e-14 (t-test), Q value = 1e-11

Table S25. Clustering Approach #14: 'Del Peak 18(15q25.3) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	225	2.8 (5.2)
DEL PEAK 18(15Q25.3) MUTATED	4	0.0 (0.0)
DEL PEAK 18(15Q25.3) WILD-TYPE	221	2.9 (5.3)

Figure S11. Get High-res Image Clustering Approach #14: 'Del Peak 18(15q25.3) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

Clustering Approach #15: 'Del Peak 20(16q23.3) mutation analysis'

Table S26. Description of clustering approach #15: 'Del Peak 20(16q23.3) mutation analysis'

Cluster Labels	DEL PEAK 20(16Q23.3) MUTATED	DEL PEAK 20(16Q23.3) WILD-TYPE
Number of samples	3	281

Clustering Approach #16: 'Del Peak 21(17p13.1) mutation analysis'

Table S27. Description of clustering approach #16: 'Del Peak 21(17p13.1) mutation analysis'

Cluster Labels	DEL PEAK 21(17P13.1) MUTATED	DEL PEAK 21(17P13.1) WILD-TYPE
Number of samples	5	279

Clustering Approach #17: 'Del Peak 22(18p11.21) mutation analysis'

Table S28. Description of clustering approach #17: 'Del Peak 22(18p11.21) mutation analysis'

Cluster Labels	DEL PEAK 22(18P11.21) MUTATED	DEL PEAK 22(18P11.21) WILD-TYPE
Number of samples	3	281

Clustering Approach #18: 'Del Peak 23(19p13.2) mutation analysis'

Table S29. Description of clustering approach #18: 'Del Peak 23(19p13.2) mutation analysis'

Cluster Labels	DEL PEAK 23(19P13.2) MUTATED	DEL PEAK 23(19P13.2) WILD-TYPE
Number of samples	4	280

Clustering Approach #19: 'Del Peak 26(21q21.1) mutation analysis'

Table S30. Description of clustering approach #19: 'Del Peak 26(21q21.1) mutation analysis'

Cluster Labels	DEL PEAK 26(21Q21.1) MUTATED	DEL PEAK 26(21Q21.1) WILD-TYPE
Number of samples	7	277

'Del Peak 26(21q21.1) mutation analysis' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.000339 (Chi-square test), Q value = 0.11

Table S31. Clustering Approach #19: 'Del Peak 26(21q21.1) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IVA	STAGE IVC
ALL	161	32	62	25	3
DEL PEAK 26(21Q21.1) MUTATED	0	4	1	2	0
DEL PEAK 26(21Q21.1) WILD-TYPE	161	28	61	23	3

Figure S12. Get High-res Image Clustering Approach #19: 'Del Peak 26(21q21.1) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #20: 'Del Peak 27(22q13.31) mutation analysis'

Table S32. Description of clustering approach #20: 'Del Peak 27(22q13.31) mutation analysis'

Cluster Labels	DEL PEAK 27(22Q13.31) MUTATED	DEL PEAK 27(22Q13.31) WILD-TYPE
Number of samples	49	235

Clustering Approach #21: 'Del Peak 28(22q13.2) mutation analysis'

Table S33. Description of clustering approach #21: 'Del Peak 28(22q13.2) mutation analysis'

Cluster Labels	DEL PEAK 28(22Q13.2) MUTATED	DEL PEAK 28(22Q13.2) WILD-TYPE
Number of samples	49	235

Clustering Approach #22: 'Del Peak 29(22q13.32) mutation analysis'

Table S34. Description of clustering approach #22: 'Del Peak 29(22q13.32) mutation analysis'

Cluster Labels	DEL PEAK 29(22Q13.32) MUTATED	DEL PEAK 29(22Q13.32) WILD-TYPE
Number of samples	50	234

Clustering Approach #23: 'Del Peak 30(Xq22.1) mutation analysis'

Table S35. Description of clustering approach #23: 'Del Peak 30(Xq22.1) mutation analysis'

Cluster Labels	DEL PEAK 30(XQ22.1) MUTATED	DEL PEAK 30(XQ22.1) WILD-TYPE
Number of samples	6	278

'Del Peak 30(Xq22.1) mutation analysis' versus 'NEOPLASM.DISEASESTAGE'

P value = 0.000772 (Chi-square test), Q value = 0.25

Table S36. Clustering Approach #23: 'Del Peak 30(Xq22.1) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IVA	STAGE IVC
ALL	161	32	62	25	3
DEL PEAK 30(XQ22.1) MUTATED	1	4	1	0	0
DEL PEAK 30(XQ22.1) WILD-TYPE	160	28	61	25	3

Figure S13. Get High-res Image Clustering Approach #23: 'Del Peak 30(Xq22.1) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

Clustering Approach #24: 'Del Peak 31(Xq22.3) mutation analysis'

Table S37. Description of clustering approach #24: 'Del Peak 31(Xq22.3) mutation analysis'

Cluster Labels	DEL PEAK 31(XQ22.3) MUTATED	DEL PEAK 31(XQ22.3) WILD-TYPE
Number of samples	4	280

'Del Peak 31(Xq22.3) mutation analysis' versus 'NUMBER.OF.LYMPH.NODES'

P value = 3.02e-14 (t-test), Q value = 1e-11

Table S38. Clustering Approach #24: 'Del Peak 31(Xq22.3) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	225	2.8 (5.2)
DEL PEAK 31(XQ22.3) MUTATED	4	0.0 (0.0)
DEL PEAK 31(XQ22.3) WILD-TYPE	221	2.9 (5.3)

Figure S14. Get High-res Image Clustering Approach #24: 'Del Peak 31(Xq22.3) mutation analysis' versus Clinical Feature #11: 'NUMBER.OF.LYMPH.NODES'

'Del Peak 31(Xq22.3) mutation analysis' versus 'NEOPLASM.DISEASESTAGE'

P value = 2.08e-06 (Chi-square test), Q value = 0.00068

Table S39. Clustering Approach #24: 'Del Peak 31(Xq22.3) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE III	STAGE IVA	STAGE IVC
ALL	161	32	62	25	3
DEL PEAK 31(XQ22.3) MUTATED	0	4	0	0	0
DEL PEAK 31(XQ22.3) WILD-TYPE	161	28	62	25	3

Figure S15. Get High-res Image Clustering Approach #24: 'Del Peak 31(Xq22.3) mutation analysis' versus Clinical Feature #13: 'NEOPLASM.DISEASESTAGE'

Methods & Data

Input

Cluster data file = all_lesions.conf_99.cnv.cluster.txt
Clinical data file = THCA-TP.clin.merged.picked.txt
Number of patients = 284
Number of clustering approaches = 24
Number of selected clinical features = 15
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

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

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

[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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