This pipeline computes the correlation between significant copy number variation (cnv) genes and selected clinical features.
Testing the association between copy number variation of 86 peak regions and 5 clinical features across 820 patients, 6 significant findings detected with Q value < 0.25.
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Del Peak 2(1p21.2) cnvs correlated to 'AGE'.
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Del Peak 16(6q27) cnvs correlated to 'AGE'.
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Del Peak 22(9p23) cnvs correlated to 'Time to Death'.
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Del Peak 39(16q11.2) cnvs correlated to 'AGE'.
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Del Peak 40(16q23.1) cnvs correlated to 'AGE'.
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Del Peak 41(16q24.3) cnvs correlated to 'AGE'.
Table 1. Get Full Table Overview of the association between significant copy number variation of 86 regions and 5 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 6 significant findings detected.
|
Clinical Features |
Time to Death |
AGE | GENDER |
RADIATIONS RADIATION REGIMENINDICATION |
NEOADJUVANT THERAPY |
||
| nCNV (%) | nWild-Type | logrank test | t-test | Fisher's exact test | Fisher's exact test | Fisher's exact test | |
| Del Peak 2(1p21 2) | 181 (22%) | 639 |
0.234 (1.00) |
0.000453 (0.193) |
1 (1.00) |
0.552 (1.00) |
0.381 (1.00) |
| Del Peak 16(6q27) | 218 (27%) | 602 |
0.212 (1.00) |
0.000285 (0.122) |
0.458 (1.00) |
0.262 (1.00) |
0.51 (1.00) |
| Del Peak 22(9p23) | 185 (23%) | 635 |
0.00037 (0.158) |
0.143 (1.00) |
0.43 (1.00) |
0.238 (1.00) |
0.0677 (1.00) |
| Del Peak 39(16q11 2) | 355 (43%) | 465 |
0.271 (1.00) |
0.000556 (0.236) |
1 (1.00) |
0.36 (1.00) |
0.714 (1.00) |
| Del Peak 40(16q23 1) | 431 (53%) | 389 |
0.0798 (1.00) |
6.57e-05 (0.0282) |
1 (1.00) |
0.321 (1.00) |
0.56 (1.00) |
| Del Peak 41(16q24 3) | 433 (53%) | 387 |
0.232 (1.00) |
2.83e-05 (0.0122) |
0.512 (1.00) |
0.363 (1.00) |
0.611 (1.00) |
| Amp Peak 1(1p22 3) | 134 (16%) | 686 |
0.703 (1.00) |
0.795 (1.00) |
0.646 (1.00) |
0.824 (1.00) |
0.556 (1.00) |
| Amp Peak 2(1q21 3) | 529 (65%) | 291 |
0.41 (1.00) |
0.274 (1.00) |
0.728 (1.00) |
0.0698 (1.00) |
0.649 (1.00) |
| Amp Peak 3(1q32 1) | 554 (68%) | 266 |
0.0569 (1.00) |
0.495 (1.00) |
0.285 (1.00) |
0.251 (1.00) |
0.938 (1.00) |
| Amp Peak 4(3p25 1) | 103 (13%) | 717 |
0.00966 (1.00) |
0.332 (1.00) |
0.612 (1.00) |
1 (1.00) |
0.382 (1.00) |
| Amp Peak 5(3q26 32) | 195 (24%) | 625 |
0.498 (1.00) |
0.311 (1.00) |
0.694 (1.00) |
0.383 (1.00) |
0.609 (1.00) |
| Amp Peak 6(4q13 3) | 95 (12%) | 725 |
0.0301 (1.00) |
0.83 (1.00) |
1 (1.00) |
0.608 (1.00) |
0.571 (1.00) |
| Amp Peak 7(6p23) | 163 (20%) | 657 |
0.908 (1.00) |
0.737 (1.00) |
1 (1.00) |
0.302 (1.00) |
0.785 (1.00) |
| Amp Peak 8(6q21) | 110 (13%) | 710 |
0.000948 (0.402) |
0.63 (1.00) |
1 (1.00) |
0.904 (1.00) |
0.75 (1.00) |
| Amp Peak 9(7p11 2) | 173 (21%) | 647 |
0.988 (1.00) |
0.149 (1.00) |
0.0997 (1.00) |
0.0336 (1.00) |
0.0409 (1.00) |
| Amp Peak 10(8p11 23) | 264 (32%) | 556 |
0.029 (1.00) |
0.00542 (1.00) |
0.285 (1.00) |
0.659 (1.00) |
0.816 (1.00) |
| Amp Peak 11(8p11 23) | 256 (31%) | 564 |
0.208 (1.00) |
0.00372 (1.00) |
0.287 (1.00) |
0.593 (1.00) |
0.695 (1.00) |
| Amp Peak 12(8p11 21) | 266 (32%) | 554 |
0.896 (1.00) |
0.00189 (0.799) |
0.285 (1.00) |
0.0104 (1.00) |
0.278 (1.00) |
| Amp Peak 13(8q21 13) | 421 (51%) | 399 |
0.559 (1.00) |
0.0431 (1.00) |
0.507 (1.00) |
0.116 (1.00) |
0.562 (1.00) |
| Amp Peak 14(8q24 21) | 484 (59%) | 336 |
0.182 (1.00) |
0.78 (1.00) |
0.744 (1.00) |
0.615 (1.00) |
0.605 (1.00) |
| Amp Peak 15(10p15 1) | 166 (20%) | 654 |
0.25 (1.00) |
0.828 (1.00) |
0.217 (1.00) |
0.537 (1.00) |
0.527 (1.00) |
| Amp Peak 16(10q22 3) | 83 (10%) | 737 |
0.0694 (1.00) |
0.287 (1.00) |
0.61 (1.00) |
1 (1.00) |
1 (1.00) |
| Amp Peak 17(10q26 13) | 64 (8%) | 756 |
0.517 (1.00) |
0.545 (1.00) |
1 (1.00) |
0.758 (1.00) |
0.343 (1.00) |
| Amp Peak 18(11p13) | 116 (14%) | 704 |
0.54 (1.00) |
0.96 (1.00) |
0.371 (1.00) |
0.238 (1.00) |
0.677 (1.00) |
| Amp Peak 19(11q13 3) | 263 (32%) | 557 |
0.158 (1.00) |
0.334 (1.00) |
0.155 (1.00) |
0.658 (1.00) |
0.586 (1.00) |
| Amp Peak 20(11q14 1) | 159 (19%) | 661 |
0.0628 (1.00) |
0.255 (1.00) |
0.688 (1.00) |
0.601 (1.00) |
0.198 (1.00) |
| Amp Peak 21(12p13 33) | 148 (18%) | 672 |
0.736 (1.00) |
0.919 (1.00) |
1 (1.00) |
0.164 (1.00) |
0.777 (1.00) |
| Amp Peak 22(12q15) | 158 (19%) | 662 |
0.0577 (1.00) |
0.212 (1.00) |
0.00236 (0.987) |
0.917 (1.00) |
0.519 (1.00) |
| Amp Peak 23(13q12 3) | 82 (10%) | 738 |
0.0709 (1.00) |
0.982 (1.00) |
0.225 (1.00) |
0.784 (1.00) |
0.718 (1.00) |
| Amp Peak 24(13q34) | 93 (11%) | 727 |
0.929 (1.00) |
0.542 (1.00) |
0.608 (1.00) |
0.897 (1.00) |
0.647 (1.00) |
| Amp Peak 25(14q21 1) | 128 (16%) | 692 |
0.933 (1.00) |
0.39 (1.00) |
1 (1.00) |
0.427 (1.00) |
0.109 (1.00) |
| Amp Peak 26(15q26 3) | 109 (13%) | 711 |
0.131 (1.00) |
0.0729 (1.00) |
0.105 (1.00) |
1 (1.00) |
1 (1.00) |
| Amp Peak 27(16q12 1) | 106 (13%) | 714 |
0.0326 (1.00) |
0.0121 (1.00) |
1 (1.00) |
0.622 (1.00) |
0.829 (1.00) |
| Amp Peak 28(17p11 2) | 80 (10%) | 740 |
0.318 (1.00) |
0.00261 (1.00) |
0.216 (1.00) |
0.678 (1.00) |
0.392 (1.00) |
| Amp Peak 29(17q12) | 222 (27%) | 598 |
0.663 (1.00) |
0.875 (1.00) |
0.00212 (0.887) |
0.308 (1.00) |
0.141 (1.00) |
| Amp Peak 30(17q23 1) | 281 (34%) | 539 |
0.634 (1.00) |
0.506 (1.00) |
0.00112 (0.475) |
0.223 (1.00) |
0.00466 (1.00) |
| Amp Peak 31(19q12) | 124 (15%) | 696 |
0.312 (1.00) |
0.785 (1.00) |
0.632 (1.00) |
0.107 (1.00) |
0.839 (1.00) |
| Amp Peak 32(19q13 42) | 129 (16%) | 691 |
0.519 (1.00) |
0.917 (1.00) |
0.156 (1.00) |
0.821 (1.00) |
0.842 (1.00) |
| Amp Peak 33(20q13 2) | 330 (40%) | 490 |
0.0805 (1.00) |
0.753 (1.00) |
0.497 (1.00) |
0.737 (1.00) |
0.657 (1.00) |
| Del Peak 1(1p36 13) | 243 (30%) | 577 |
0.0866 (1.00) |
0.0254 (1.00) |
0.135 (1.00) |
0.176 (1.00) |
0.301 (1.00) |
| Del Peak 3(2p25 1) | 84 (10%) | 736 |
0.773 (1.00) |
0.0897 (1.00) |
1 (1.00) |
1 (1.00) |
0.231 (1.00) |
| Del Peak 4(2q22 3) | 106 (13%) | 714 |
0.958 (1.00) |
0.624 (1.00) |
1 (1.00) |
0.622 (1.00) |
1 (1.00) |
| Del Peak 5(2q36 3) | 121 (15%) | 699 |
0.116 (1.00) |
0.765 (1.00) |
0.37 (1.00) |
0.487 (1.00) |
0.919 (1.00) |
| Del Peak 6(2q37 3) | 138 (17%) | 682 |
0.232 (1.00) |
0.895 (1.00) |
1 (1.00) |
0.826 (1.00) |
0.698 (1.00) |
| Del Peak 7(3p21 31) | 207 (25%) | 613 |
0.00749 (1.00) |
0.00195 (0.82) |
0.241 (1.00) |
0.85 (1.00) |
0.676 (1.00) |
| Del Peak 8(3p13) | 185 (23%) | 635 |
0.00642 (1.00) |
0.0119 (1.00) |
0.43 (1.00) |
0.168 (1.00) |
0.339 (1.00) |
| Del Peak 9(4p16 3) | 172 (21%) | 648 |
0.765 (1.00) |
0.243 (1.00) |
1 (1.00) |
0.919 (1.00) |
0.109 (1.00) |
| Del Peak 10(4q35 2) | 169 (21%) | 651 |
0.141 (1.00) |
0.48 (1.00) |
0.694 (1.00) |
0.838 (1.00) |
0.243 (1.00) |
| Del Peak 11(5q11 2) | 155 (19%) | 665 |
0.129 (1.00) |
0.0603 (1.00) |
0.221 (1.00) |
1 (1.00) |
0.516 (1.00) |
| Del Peak 12(5q21 3) | 149 (18%) | 671 |
0.44 (1.00) |
0.163 (1.00) |
0.377 (1.00) |
0.668 (1.00) |
0.158 (1.00) |
| Del Peak 13(6p25 3) | 103 (13%) | 717 |
0.954 (1.00) |
0.403 (1.00) |
0.315 (1.00) |
0.619 (1.00) |
0.662 (1.00) |
| Del Peak 14(6q14 3) | 223 (27%) | 597 |
0.547 (1.00) |
0.195 (1.00) |
0.457 (1.00) |
0.578 (1.00) |
0.624 (1.00) |
| Del Peak 15(6q21) | 220 (27%) | 600 |
0.605 (1.00) |
0.00883 (1.00) |
0.708 (1.00) |
0.78 (1.00) |
0.935 (1.00) |
| Del Peak 17(7p22 3) | 72 (9%) | 748 |
0.836 (1.00) |
0.677 (1.00) |
1 (1.00) |
0.381 (1.00) |
0.307 (1.00) |
| Del Peak 18(7q36 1) | 118 (14%) | 702 |
0.114 (1.00) |
0.538 (1.00) |
0.625 (1.00) |
0.346 (1.00) |
0.471 (1.00) |
| Del Peak 19(8p23 2) | 388 (47%) | 432 |
0.204 (1.00) |
0.367 (1.00) |
0.321 (1.00) |
0.0686 (1.00) |
0.146 (1.00) |
| Del Peak 20(8p12) | 310 (38%) | 510 |
0.182 (1.00) |
0.799 (1.00) |
0.495 (1.00) |
0.126 (1.00) |
0.202 (1.00) |
| Del Peak 21(8p11 21) | 121 (15%) | 699 |
0.0301 (1.00) |
0.567 (1.00) |
0.37 (1.00) |
0.0623 (1.00) |
0.184 (1.00) |
| Del Peak 23(9p21 3) | 217 (26%) | 603 |
0.0406 (1.00) |
0.291 (1.00) |
0.255 (1.00) |
0.261 (1.00) |
0.00295 (1.00) |
| Del Peak 24(9q21 11) | 144 (18%) | 676 |
0.251 (1.00) |
0.0666 (1.00) |
0.199 (1.00) |
0.664 (1.00) |
0.00411 (1.00) |
| Del Peak 25(10q23 31) | 157 (19%) | 663 |
0.351 (1.00) |
0.73 (1.00) |
0.22 (1.00) |
0.464 (1.00) |
0.407 (1.00) |
| Del Peak 26(10q26 3) | 151 (18%) | 669 |
0.00421 (1.00) |
0.236 (1.00) |
1 (1.00) |
0.915 (1.00) |
0.708 (1.00) |
| Del Peak 27(11p15 5) | 169 (21%) | 651 |
0.00472 (1.00) |
0.525 (1.00) |
0.401 (1.00) |
0.683 (1.00) |
0.529 (1.00) |
| Del Peak 28(11q13 1) | 124 (15%) | 696 |
0.329 (1.00) |
0.408 (1.00) |
0.632 (1.00) |
0.73 (1.00) |
0.478 (1.00) |
| Del Peak 29(11q23 3) | 344 (42%) | 476 |
0.156 (1.00) |
0.749 (1.00) |
0.0397 (1.00) |
0.867 (1.00) |
0.941 (1.00) |
| Del Peak 30(11q25) | 315 (38%) | 505 |
0.0802 (1.00) |
0.861 (1.00) |
0.0315 (1.00) |
0.799 (1.00) |
0.654 (1.00) |
| Del Peak 31(12p13 1) | 105 (13%) | 715 |
0.234 (1.00) |
0.351 (1.00) |
0.324 (1.00) |
0.459 (1.00) |
0.328 (1.00) |
| Del Peak 32(12q23 1) | 90 (11%) | 730 |
0.928 (1.00) |
0.983 (1.00) |
0.608 (1.00) |
0.509 (1.00) |
0.0146 (1.00) |
| Del Peak 33(12q24 32) | 101 (12%) | 719 |
0.817 (1.00) |
0.616 (1.00) |
0.611 (1.00) |
0.9 (1.00) |
0.121 (1.00) |
| Del Peak 34(13q12 11) | 239 (29%) | 581 |
0.286 (1.00) |
0.344 (1.00) |
0.725 (1.00) |
0.102 (1.00) |
0.472 (1.00) |
| Del Peak 35(13q14 2) | 289 (35%) | 531 |
0.181 (1.00) |
0.649 (1.00) |
0.291 (1.00) |
0.545 (1.00) |
0.939 (1.00) |
| Del Peak 36(14q24 3) | 182 (22%) | 638 |
0.0419 (1.00) |
0.62 (1.00) |
0.424 (1.00) |
0.691 (1.00) |
0.256 (1.00) |
| Del Peak 37(15q11 2) | 197 (24%) | 623 |
0.616 (1.00) |
0.836 (1.00) |
0.124 (1.00) |
1 (1.00) |
0.308 (1.00) |
| Del Peak 38(15q21 1) | 192 (23%) | 628 |
0.206 (1.00) |
0.596 (1.00) |
0.693 (1.00) |
1 (1.00) |
0.732 (1.00) |
| Del Peak 42(17p13 3) | 380 (46%) | 440 |
0.276 (1.00) |
0.00654 (1.00) |
0.74 (1.00) |
0.0828 (1.00) |
0.145 (1.00) |
| Del Peak 43(17p12) | 407 (50%) | 413 |
0.251 (1.00) |
0.0449 (1.00) |
0.105 (1.00) |
0.0827 (1.00) |
0.216 (1.00) |
| Del Peak 44(17p11 2) | 289 (35%) | 531 |
0.329 (1.00) |
0.00392 (1.00) |
0.291 (1.00) |
0.226 (1.00) |
0.447 (1.00) |
| Del Peak 45(17q12) | 210 (26%) | 610 |
0.597 (1.00) |
0.00879 (1.00) |
0.461 (1.00) |
0.156 (1.00) |
0.454 (1.00) |
| Del Peak 46(17q21 31) | 219 (27%) | 601 |
0.447 (1.00) |
0.0168 (1.00) |
0.458 (1.00) |
0.304 (1.00) |
0.326 (1.00) |
| Del Peak 47(18q23) | 201 (25%) | 619 |
0.0443 (1.00) |
0.0817 (1.00) |
0.464 (1.00) |
1 (1.00) |
0.866 (1.00) |
| Del Peak 48(19p13 3) | 185 (23%) | 635 |
0.924 (1.00) |
0.31 (1.00) |
0.692 (1.00) |
0.621 (1.00) |
0.259 (1.00) |
| Del Peak 49(19q13 32) | 79 (10%) | 741 |
0.348 (1.00) |
0.324 (1.00) |
1 (1.00) |
0.78 (1.00) |
0.622 (1.00) |
| Del Peak 50(20p13) | 89 (11%) | 731 |
0.00208 (0.873) |
0.27 (1.00) |
1 (1.00) |
0.509 (1.00) |
0.0618 (1.00) |
| Del Peak 51(21q11 2) | 109 (13%) | 711 |
0.872 (1.00) |
0.296 (1.00) |
0.616 (1.00) |
1 (1.00) |
0.0318 (1.00) |
| Del Peak 52(22q11 1) | 259 (32%) | 561 |
0.0596 (1.00) |
0.706 (1.00) |
0.727 (1.00) |
0.0623 (1.00) |
0.585 (1.00) |
| Del Peak 53(22q13 31) | 286 (35%) | 534 |
0.358 (1.00) |
0.398 (1.00) |
0.29 (1.00) |
0.386 (1.00) |
0.36 (1.00) |
P value = 0.000453 (t-test), Q value = 0.19
Table S1. Gene #35: 'Del Peak 2(1p21.2) mutation analysis' versus Clinical Feature #2: 'AGE'
| nPatients | Mean (Std.Dev) | |
|---|---|---|
| ALL | 819 | 58.4 (13.2) |
| DEL PEAK 2(1P21.2) MUTATED | 181 | 61.4 (13.2) |
| DEL PEAK 2(1P21.2) WILD-TYPE | 638 | 57.5 (13.2) |
Figure S1. Get High-res Image Gene #35: 'Del Peak 2(1p21.2) mutation analysis' versus Clinical Feature #2: 'AGE'
P value = 0.000285 (t-test), Q value = 0.12
Table S2. Gene #49: 'Del Peak 16(6q27) mutation analysis' versus Clinical Feature #2: 'AGE'
| nPatients | Mean (Std.Dev) | |
|---|---|---|
| ALL | 819 | 58.4 (13.2) |
| DEL PEAK 16(6Q27) MUTATED | 218 | 55.6 (12.9) |
| DEL PEAK 16(6Q27) WILD-TYPE | 601 | 59.4 (13.3) |
Figure S2. Get High-res Image Gene #49: 'Del Peak 16(6q27) mutation analysis' versus Clinical Feature #2: 'AGE'
P value = 0.00037 (logrank test), Q value = 0.16
Table S3. Gene #55: 'Del Peak 22(9p23) mutation analysis' versus Clinical Feature #1: 'Time to Death'
| nPatients | nDeath | Duration Range (Median), Month | |
|---|---|---|---|
| ALL | 762 | 93 | 0.0 - 223.4 (18.4) |
| DEL PEAK 22(9P23) MUTATED | 170 | 26 | 0.1 - 162.0 (15.8) |
| DEL PEAK 22(9P23) WILD-TYPE | 592 | 67 | 0.0 - 223.4 (19.7) |
Figure S3. Get High-res Image Gene #55: 'Del Peak 22(9p23) mutation analysis' versus Clinical Feature #1: 'Time to Death'
P value = 0.000556 (t-test), Q value = 0.24
Table S4. Gene #72: 'Del Peak 39(16q11.2) mutation analysis' versus Clinical Feature #2: 'AGE'
| nPatients | Mean (Std.Dev) | |
|---|---|---|
| ALL | 819 | 58.4 (13.2) |
| DEL PEAK 39(16Q11.2) MUTATED | 355 | 60.2 (12.8) |
| DEL PEAK 39(16Q11.2) WILD-TYPE | 464 | 57.0 (13.4) |
Figure S4. Get High-res Image Gene #72: 'Del Peak 39(16q11.2) mutation analysis' versus Clinical Feature #2: 'AGE'
P value = 6.57e-05 (t-test), Q value = 0.028
Table S5. Gene #73: 'Del Peak 40(16q23.1) mutation analysis' versus Clinical Feature #2: 'AGE'
| nPatients | Mean (Std.Dev) | |
|---|---|---|
| ALL | 819 | 58.4 (13.2) |
| DEL PEAK 40(16Q23.1) MUTATED | 431 | 60.1 (13.2) |
| DEL PEAK 40(16Q23.1) WILD-TYPE | 388 | 56.4 (13.0) |
Figure S5. Get High-res Image Gene #73: 'Del Peak 40(16q23.1) mutation analysis' versus Clinical Feature #2: 'AGE'
P value = 2.83e-05 (t-test), Q value = 0.012
Table S6. Gene #74: 'Del Peak 41(16q24.3) mutation analysis' versus Clinical Feature #2: 'AGE'
| nPatients | Mean (Std.Dev) | |
|---|---|---|
| ALL | 819 | 58.4 (13.2) |
| DEL PEAK 41(16Q24.3) MUTATED | 433 | 60.2 (13.2) |
| DEL PEAK 41(16Q24.3) WILD-TYPE | 386 | 56.3 (13.0) |
Figure S6. Get High-res Image Gene #74: 'Del Peak 41(16q24.3) mutation analysis' versus Clinical Feature #2: 'AGE'
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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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Clinical data file = BRCA.clin.merged.picked.txt
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Number of patients = 820
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Number of copy number variation regions = 86
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Number of selected clinical features = 5
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Exclude regions that fewer than K tumors have alterations, K = 3
For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene cnvs were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R
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 cnvs using 't.test' function in R
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 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.
This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.