This pipeline computes the correlation between significant copy number variation (cnv) genes and molecular subtypes.
Testing the association between copy number variation of 39 peak regions and 8 molecular subtypes across 112 patients, 10 significant findings detected with Q value < 0.25.
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Amp Peak 1(1p12) cnvs correlated to 'CN_CNMF'.
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Amp Peak 10(8q11.21) cnvs correlated to 'CN_CNMF'.
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Amp Peak 11(8q24.21) cnvs correlated to 'CN_CNMF'.
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Del Peak 2(1p21.3) cnvs correlated to 'MRNASEQ_CNMF'.
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Del Peak 7(6q25.3) cnvs correlated to 'CN_CNMF'.
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Del Peak 8(6q26) cnvs correlated to 'CN_CNMF'.
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Del Peak 10(9p23) cnvs correlated to 'CN_CNMF'.
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Del Peak 11(9p21.3) cnvs correlated to 'CN_CNMF' and 'MRNASEQ_CNMF'.
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Del Peak 14(11q23.1) cnvs correlated to 'CN_CNMF'.
Table 1. Get Full Table Overview of the association between significant copy number variation of 39 regions and 8 molecular subtypes. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 10 significant findings detected.
|
Molecular subtypes |
CN CNMF |
METHLYATION CNMF |
RPPA CNMF |
RPPA CHIERARCHICAL |
MRNASEQ CNMF |
MRNASEQ CHIERARCHICAL |
MIRSEQ CNMF |
MIRSEQ CHIERARCHICAL |
||
| nCNV (%) | nWild-Type | Fisher's exact test | Fisher's exact test | Chi-square test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | |
| Del Peak 11(9p21 3) | 86 (77%) | 26 |
0.000155 (0.0475) |
0.0288 (1.00) |
0.0848 (1.00) |
0.811 (1.00) |
2.39e-05 (0.00735) |
0.00169 (0.498) |
0.308 (1.00) |
0.229 (1.00) |
| Amp Peak 1(1p12) | 32 (29%) | 80 |
8.51e-05 (0.0261) |
0.225 (1.00) |
0.812 (1.00) |
0.113 (1.00) |
0.0204 (1.00) |
0.185 (1.00) |
0.297 (1.00) |
0.158 (1.00) |
| Amp Peak 10(8q11 21) | 41 (37%) | 71 |
1.3e-05 (0.00404) |
0.00223 (0.65) |
0.417 (1.00) |
0.218 (1.00) |
0.191 (1.00) |
0.0317 (1.00) |
0.0715 (1.00) |
0.0711 (1.00) |
| Amp Peak 11(8q24 21) | 50 (45%) | 62 |
0.000343 (0.104) |
0.0122 (1.00) |
0.737 (1.00) |
0.399 (1.00) |
0.046 (1.00) |
0.173 (1.00) |
0.317 (1.00) |
0.524 (1.00) |
| Del Peak 2(1p21 3) | 30 (27%) | 82 |
0.14 (1.00) |
0.0165 (1.00) |
0.36 (1.00) |
0.164 (1.00) |
0.000327 (0.0993) |
0.00195 (0.574) |
0.646 (1.00) |
0.891 (1.00) |
| Del Peak 7(6q25 3) | 67 (60%) | 45 |
2.85e-09 (8.89e-07) |
0.00557 (1.00) |
0.145 (1.00) |
0.335 (1.00) |
0.0261 (1.00) |
0.454 (1.00) |
0.102 (1.00) |
0.718 (1.00) |
| Del Peak 8(6q26) | 63 (56%) | 49 |
2.44e-08 (7.59e-06) |
0.0238 (1.00) |
0.269 (1.00) |
0.288 (1.00) |
0.0689 (1.00) |
0.193 (1.00) |
0.356 (1.00) |
0.912 (1.00) |
| Del Peak 10(9p23) | 75 (67%) | 37 |
1.32e-05 (0.00408) |
0.277 (1.00) |
0.662 (1.00) |
0.677 (1.00) |
0.00283 (0.82) |
0.0756 (1.00) |
0.782 (1.00) |
0.377 (1.00) |
| Del Peak 14(11q23 1) | 61 (54%) | 51 |
0.000236 (0.072) |
0.176 (1.00) |
0.516 (1.00) |
0.787 (1.00) |
0.0402 (1.00) |
0.00127 (0.378) |
0.0102 (1.00) |
0.482 (1.00) |
| Amp Peak 2(1q44) | 54 (48%) | 58 |
0.0154 (1.00) |
0.417 (1.00) |
0.643 (1.00) |
0.919 (1.00) |
0.061 (1.00) |
0.278 (1.00) |
0.0568 (1.00) |
0.529 (1.00) |
| Amp Peak 3(3p13) | 24 (21%) | 88 |
0.0168 (1.00) |
0.192 (1.00) |
0.101 (1.00) |
0.0377 (1.00) |
0.229 (1.00) |
0.00754 (1.00) |
0.406 (1.00) |
0.325 (1.00) |
| Amp Peak 4(5p15 33) | 32 (29%) | 80 |
0.0125 (1.00) |
0.0565 (1.00) |
0.78 (1.00) |
0.742 (1.00) |
0.93 (1.00) |
0.584 (1.00) |
0.0304 (1.00) |
0.717 (1.00) |
| Amp Peak 5(5q35 3) | 13 (12%) | 99 |
0.00113 (0.341) |
0.033 (1.00) |
0.215 (1.00) |
0.774 (1.00) |
0.288 (1.00) |
0.422 (1.00) |
0.216 (1.00) |
0.895 (1.00) |
| Amp Peak 6(6p25 1) | 61 (54%) | 51 |
0.00618 (1.00) |
0.00163 (0.483) |
0.286 (1.00) |
0.246 (1.00) |
0.97 (1.00) |
0.336 (1.00) |
0.36 (1.00) |
0.032 (1.00) |
| Amp Peak 7(6q12) | 23 (21%) | 89 |
0.292 (1.00) |
0.545 (1.00) |
0.495 (1.00) |
0.979 (1.00) |
0.0469 (1.00) |
0.18 (1.00) |
0.0573 (1.00) |
0.536 (1.00) |
| Amp Peak 8(7p22 1) | 60 (54%) | 52 |
0.00212 (0.621) |
0.524 (1.00) |
0.971 (1.00) |
0.77 (1.00) |
0.127 (1.00) |
0.703 (1.00) |
0.707 (1.00) |
0.662 (1.00) |
| Amp Peak 9(7q34) | 62 (55%) | 50 |
0.00136 (0.403) |
0.438 (1.00) |
0.34 (1.00) |
0.951 (1.00) |
0.761 (1.00) |
0.295 (1.00) |
0.279 (1.00) |
0.524 (1.00) |
| Amp Peak 12(9p24 1) | 5 (4%) | 107 |
0.116 (1.00) |
0.511 (1.00) |
0.676 (1.00) |
0.536 (1.00) |
0.365 (1.00) |
0.0675 (1.00) |
1 (1.00) |
0.606 (1.00) |
| Amp Peak 13(11q13 3) | 19 (17%) | 93 |
0.146 (1.00) |
0.361 (1.00) |
0.163 (1.00) |
0.971 (1.00) |
0.114 (1.00) |
0.0617 (1.00) |
1 (1.00) |
0.53 (1.00) |
| Amp Peak 14(12q14 1) | 20 (18%) | 92 |
0.00275 (0.801) |
0.123 (1.00) |
0.119 (1.00) |
0.238 (1.00) |
0.157 (1.00) |
0.391 (1.00) |
0.773 (1.00) |
0.366 (1.00) |
| Amp Peak 15(15q26 2) | 43 (38%) | 69 |
0.176 (1.00) |
0.655 (1.00) |
0.752 (1.00) |
0.511 (1.00) |
0.566 (1.00) |
0.0559 (1.00) |
0.585 (1.00) |
0.647 (1.00) |
| Amp Peak 16(17q25 3) | 44 (39%) | 68 |
0.00125 (0.375) |
0.0441 (1.00) |
0.956 (1.00) |
0.554 (1.00) |
0.486 (1.00) |
0.0809 (1.00) |
0.00116 (0.35) |
0.869 (1.00) |
| Amp Peak 17(19p13 2) | 19 (17%) | 93 |
0.056 (1.00) |
0.011 (1.00) |
0.701 (1.00) |
0.096 (1.00) |
0.0444 (1.00) |
0.369 (1.00) |
0.52 (1.00) |
0.238 (1.00) |
| Amp Peak 18(22q13 2) | 48 (43%) | 64 |
0.234 (1.00) |
0.806 (1.00) |
0.85 (1.00) |
1 (1.00) |
0.543 (1.00) |
0.248 (1.00) |
0.543 (1.00) |
0.956 (1.00) |
| Del Peak 1(1p36 31) | 27 (24%) | 85 |
0.0887 (1.00) |
0.102 (1.00) |
0.235 (1.00) |
0.385 (1.00) |
0.00413 (1.00) |
0.0652 (1.00) |
0.378 (1.00) |
0.424 (1.00) |
| Del Peak 3(2q37 3) | 21 (19%) | 91 |
0.531 (1.00) |
0.171 (1.00) |
0.562 (1.00) |
0.413 (1.00) |
0.1 (1.00) |
0.192 (1.00) |
0.348 (1.00) |
0.0508 (1.00) |
| Del Peak 4(3p24 3) | 17 (15%) | 95 |
0.411 (1.00) |
0.423 (1.00) |
0.183 (1.00) |
0.0654 (1.00) |
0.595 (1.00) |
0.146 (1.00) |
0.388 (1.00) |
0.837 (1.00) |
| Del Peak 5(4q34 3) | 23 (21%) | 89 |
0.0542 (1.00) |
0.308 (1.00) |
0.532 (1.00) |
0.797 (1.00) |
0.351 (1.00) |
0.976 (1.00) |
0.47 (1.00) |
0.325 (1.00) |
| Del Peak 6(5q31 3) | 45 (40%) | 67 |
0.0636 (1.00) |
0.0943 (1.00) |
0.646 (1.00) |
0.511 (1.00) |
0.208 (1.00) |
0.761 (1.00) |
0.212 (1.00) |
0.25 (1.00) |
| Del Peak 9(8p23 3) | 29 (26%) | 83 |
0.108 (1.00) |
0.0808 (1.00) |
0.0735 (1.00) |
0.0634 (1.00) |
0.559 (1.00) |
0.451 (1.00) |
0.463 (1.00) |
0.588 (1.00) |
| Del Peak 12(10p15 3) | 55 (49%) | 57 |
0.00118 (0.353) |
0.121 (1.00) |
0.441 (1.00) |
0.233 (1.00) |
0.0614 (1.00) |
0.048 (1.00) |
0.301 (1.00) |
0.695 (1.00) |
| Del Peak 13(10q23 31) | 64 (57%) | 48 |
0.107 (1.00) |
0.157 (1.00) |
0.543 (1.00) |
0.122 (1.00) |
0.0131 (1.00) |
0.00446 (1.00) |
0.00536 (1.00) |
0.165 (1.00) |
| Del Peak 15(12q24 33) | 21 (19%) | 91 |
0.61 (1.00) |
0.197 (1.00) |
0.417 (1.00) |
0.764 (1.00) |
0.616 (1.00) |
0.252 (1.00) |
0.814 (1.00) |
1 (1.00) |
| Del Peak 16(13q34) | 31 (28%) | 81 |
0.306 (1.00) |
0.818 (1.00) |
0.639 (1.00) |
0.965 (1.00) |
0.894 (1.00) |
0.444 (1.00) |
0.0285 (1.00) |
0.265 (1.00) |
| Del Peak 17(15q13 3) | 25 (22%) | 87 |
0.028 (1.00) |
0.496 (1.00) |
0.293 (1.00) |
0.599 (1.00) |
0.311 (1.00) |
0.526 (1.00) |
0.803 (1.00) |
1 (1.00) |
| Del Peak 18(15q15 3) | 26 (23%) | 86 |
0.0933 (1.00) |
0.731 (1.00) |
0.812 (1.00) |
0.837 (1.00) |
0.812 (1.00) |
0.989 (1.00) |
0.438 (1.00) |
0.442 (1.00) |
| Del Peak 19(16p13 3) | 22 (20%) | 90 |
0.21 (1.00) |
0.142 (1.00) |
0.89 (1.00) |
0.63 (1.00) |
0.0375 (1.00) |
0.197 (1.00) |
0.11 (1.00) |
0.81 (1.00) |
| Del Peak 20(16q12 1) | 38 (34%) | 74 |
0.106 (1.00) |
0.154 (1.00) |
0.979 (1.00) |
0.662 (1.00) |
0.158 (1.00) |
0.327 (1.00) |
0.255 (1.00) |
0.158 (1.00) |
| Del Peak 21(16q24 2) | 43 (38%) | 69 |
0.75 (1.00) |
0.253 (1.00) |
0.382 (1.00) |
0.1 (1.00) |
0.0968 (1.00) |
0.252 (1.00) |
0.0818 (1.00) |
0.422 (1.00) |
P value = 8.51e-05 (Fisher's exact test), Q value = 0.026
Table S1. Gene #1: 'Amp Peak 1(1p12) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 |
|---|---|---|---|---|
| ALL | 30 | 18 | 38 | 26 |
| AMP PEAK 1(1P12) MUTATED | 15 | 6 | 11 | 0 |
| AMP PEAK 1(1P12) WILD-TYPE | 15 | 12 | 27 | 26 |
Figure S1. Get High-res Image Gene #1: 'Amp Peak 1(1p12) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
P value = 1.3e-05 (Fisher's exact test), Q value = 0.004
Table S2. Gene #10: 'Amp Peak 10(8q11.21) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 |
|---|---|---|---|---|
| ALL | 30 | 18 | 38 | 26 |
| AMP PEAK 10(8Q11.21) MUTATED | 9 | 16 | 9 | 7 |
| AMP PEAK 10(8Q11.21) WILD-TYPE | 21 | 2 | 29 | 19 |
Figure S2. Get High-res Image Gene #10: 'Amp Peak 10(8q11.21) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
P value = 0.000343 (Fisher's exact test), Q value = 0.1
Table S3. Gene #11: 'Amp Peak 11(8q24.21) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 |
|---|---|---|---|---|
| ALL | 30 | 18 | 38 | 26 |
| AMP PEAK 11(8Q24.21) MUTATED | 13 | 15 | 9 | 13 |
| AMP PEAK 11(8Q24.21) WILD-TYPE | 17 | 3 | 29 | 13 |
Figure S3. Get High-res Image Gene #11: 'Amp Peak 11(8q24.21) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
P value = 0.000327 (Fisher's exact test), Q value = 0.099
Table S4. Gene #20: 'Del Peak 2(1p21.3) mutation analysis' versus Clinical Feature #5: 'MRNASEQ_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
|---|---|---|---|
| ALL | 42 | 27 | 43 |
| DEL PEAK 2(1P21.3) MUTATED | 19 | 1 | 10 |
| DEL PEAK 2(1P21.3) WILD-TYPE | 23 | 26 | 33 |
Figure S4. Get High-res Image Gene #20: 'Del Peak 2(1p21.3) mutation analysis' versus Clinical Feature #5: 'MRNASEQ_CNMF'
P value = 2.85e-09 (Fisher's exact test), Q value = 8.9e-07
Table S5. Gene #25: 'Del Peak 7(6q25.3) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 |
|---|---|---|---|---|
| ALL | 30 | 18 | 38 | 26 |
| DEL PEAK 7(6Q25.3) MUTATED | 23 | 10 | 9 | 25 |
| DEL PEAK 7(6Q25.3) WILD-TYPE | 7 | 8 | 29 | 1 |
Figure S5. Get High-res Image Gene #25: 'Del Peak 7(6q25.3) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
P value = 2.44e-08 (Fisher's exact test), Q value = 7.6e-06
Table S6. Gene #26: 'Del Peak 8(6q26) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 |
|---|---|---|---|---|
| ALL | 30 | 18 | 38 | 26 |
| DEL PEAK 8(6Q26) MUTATED | 21 | 10 | 8 | 24 |
| DEL PEAK 8(6Q26) WILD-TYPE | 9 | 8 | 30 | 2 |
Figure S6. Get High-res Image Gene #26: 'Del Peak 8(6q26) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
P value = 1.32e-05 (Fisher's exact test), Q value = 0.0041
Table S7. Gene #28: 'Del Peak 10(9p23) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 |
|---|---|---|---|---|
| ALL | 30 | 18 | 38 | 26 |
| DEL PEAK 10(9P23) MUTATED | 28 | 16 | 18 | 13 |
| DEL PEAK 10(9P23) WILD-TYPE | 2 | 2 | 20 | 13 |
Figure S7. Get High-res Image Gene #28: 'Del Peak 10(9p23) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
P value = 0.000155 (Fisher's exact test), Q value = 0.047
Table S8. Gene #29: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 |
|---|---|---|---|---|
| ALL | 30 | 18 | 38 | 26 |
| DEL PEAK 11(9P21.3) MUTATED | 28 | 17 | 20 | 21 |
| DEL PEAK 11(9P21.3) WILD-TYPE | 2 | 1 | 18 | 5 |
Figure S8. Get High-res Image Gene #29: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
P value = 2.39e-05 (Fisher's exact test), Q value = 0.0073
Table S9. Gene #29: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #5: 'MRNASEQ_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
|---|---|---|---|
| ALL | 42 | 27 | 43 |
| DEL PEAK 11(9P21.3) MUTATED | 39 | 12 | 35 |
| DEL PEAK 11(9P21.3) WILD-TYPE | 3 | 15 | 8 |
Figure S9. Get High-res Image Gene #29: 'Del Peak 11(9p21.3) mutation analysis' versus Clinical Feature #5: 'MRNASEQ_CNMF'
P value = 0.000236 (Fisher's exact test), Q value = 0.072
Table S10. Gene #32: 'Del Peak 14(11q23.1) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
| nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 |
|---|---|---|---|---|
| ALL | 30 | 18 | 38 | 26 |
| DEL PEAK 14(11Q23.1) MUTATED | 25 | 12 | 14 | 10 |
| DEL PEAK 14(11Q23.1) WILD-TYPE | 5 | 6 | 24 | 16 |
Figure S10. Get High-res Image Gene #32: 'Del Peak 14(11q23.1) mutation analysis' versus Clinical Feature #1: 'CN_CNMF'
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Copy number data file = All Lesions File (all_lesions.conf_##.txt, where ## is the confidence level). The all lesions file is from GISTIC pipeline and summarizes the results from the GISTIC run. It contains data about the significant regions of amplification and deletion as well as which samples are amplified or deleted in each of these regions. The identified regions are listed down the first column, and the samples are listed across the first row, starting in column 10.
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Molecular subtype file = SKCM-Regional_LN.transferedmergedcluster.txt
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Number of patients = 112
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Number of copy number variation regions = 39
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Number of molecular subtypes = 8
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Exclude regions that fewer than K tumors have alterations, K = 3
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
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
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.