This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.
Testing the association between 19971 genes and 12 clinical features across 690 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one genes.
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803 genes correlated to 'AGE'.
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KIAA1143 , KIF15 , LGALS8 , C1ORF103 , C20ORF199 , ...
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29 genes correlated to 'NEOPLASM.DISEASESTAGE'.
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C1QTNF4 , TXN , PSPN , RFFL , PLVAP , ...
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24 genes correlated to 'PATHOLOGY.T.STAGE'.
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PCDHGA1__8 , PCDHGA10__2 , PCDHGA11__2 , PCDHGA12__2 , PCDHGA2__8 , ...
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13 genes correlated to 'PATHOLOGY.N.STAGE'.
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TCP11L1 , ADA , CEBPG , KIAA0182 , ATP2A2 , ...
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541 genes correlated to 'PATHOLOGY.M.STAGE'.
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DNAH1 , TSTD1 , USF1 , C1ORF212 , XAB2 , ...
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1910 genes correlated to 'HISTOLOGICAL.TYPE'.
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FADS1 , MCAM , SCD , GJA4 , SOD1 , ...
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378 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
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METAP2 , C16ORF58 , ZNF639 , UHRF1BP1L , HMG20B , ...
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7 genes correlated to 'NUMBER.OF.LYMPH.NODES'.
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TCP11L1 , ATP2A2 , LYSMD2__1 , SEPT8 , ADA , ...
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1574 genes correlated to 'RACE'.
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SCAMP5 , DHRS7 , ISCA1 , RHD , EIF2AK4 , ...
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191 genes correlated to 'ETHNICITY'.
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LRRC66 , WDFY3__1 , ANAPC5 , C3ORF17 , NUP98 , ...
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No genes correlated to 'Time to Death', and 'GENDER'.
Complete statistical result table is provided in Supplement Table 1
Clinical feature | Statistical test | Significant genes | Associated with | Associated with | ||
---|---|---|---|---|---|---|
Time to Death | Cox regression test | N=0 | ||||
AGE | Spearman correlation test | N=803 | older | N=627 | younger | N=176 |
NEOPLASM DISEASESTAGE | Kruskal-Wallis test | N=29 | ||||
PATHOLOGY T STAGE | Spearman correlation test | N=24 | higher stage | N=22 | lower stage | N=2 |
PATHOLOGY N STAGE | Spearman correlation test | N=13 | higher stage | N=8 | lower stage | N=5 |
PATHOLOGY M STAGE | Kruskal-Wallis test | N=541 | ||||
GENDER | Wilcoxon test | N=0 | ||||
HISTOLOGICAL TYPE | Kruskal-Wallis test | N=1910 | ||||
RADIATIONS RADIATION REGIMENINDICATION | Wilcoxon test | N=378 | yes | N=378 | no | N=0 |
NUMBER OF LYMPH NODES | Spearman correlation test | N=7 | higher number.of.lymph.nodes | N=3 | lower number.of.lymph.nodes | N=4 |
RACE | Kruskal-Wallis test | N=1574 | ||||
ETHNICITY | Wilcoxon test | N=191 | not hispanic or latino | N=191 | hispanic or latino | N=0 |
Time to Death | Duration (Months) | 0-234.3 (median=21.3) |
censored | N = 608 | |
death | N = 76 | |
Significant markers | N = 0 |
AGE | Mean (SD) | 58.11 (13) |
Significant markers | N = 803 | |
pos. correlated | 627 | |
neg. correlated | 176 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
KIAA1143 | 0.3234 | 5.418e-18 | 1.08e-13 |
KIF15 | 0.3234 | 5.418e-18 | 1.08e-13 |
LGALS8 | -0.3059 | 3.56e-16 | 7.11e-12 |
C1ORF103 | 0.3037 | 5.933e-16 | 1.18e-11 |
C20ORF199 | 0.2902 | 1.218e-14 | 2.43e-10 |
SNORD12 | 0.2902 | 1.218e-14 | 2.43e-10 |
RPS2__1 | 0.2887 | 1.663e-14 | 3.32e-10 |
SNORA10 | 0.2887 | 1.663e-14 | 3.32e-10 |
SNORA64 | 0.2887 | 1.663e-14 | 3.32e-10 |
MEX3C | 0.2867 | 2.612e-14 | 5.21e-10 |
NEOPLASM.DISEASESTAGE | Labels | N |
STAGE I | 52 | |
STAGE IA | 58 | |
STAGE IB | 5 | |
STAGE II | 8 | |
STAGE IIA | 220 | |
STAGE IIB | 158 | |
STAGE III | 2 | |
STAGE IIIA | 110 | |
STAGE IIIB | 17 | |
STAGE IIIC | 46 | |
STAGE IV | 8 | |
STAGE X | 5 | |
Significant markers | N = 29 |
PATHOLOGY.T.STAGE | Mean (SD) | 1.92 (0.71) |
N | ||
1 | 183 | |
2 | 397 | |
3 | 88 | |
4 | 20 | |
Significant markers | N = 24 | |
pos. correlated | 22 | |
neg. correlated | 2 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
PCDHGA1__8 | 0.1711 | 6.378e-06 | 0.127 |
PCDHGA10__2 | 0.1711 | 6.378e-06 | 0.127 |
PCDHGA11__2 | 0.1711 | 6.378e-06 | 0.127 |
PCDHGA12__2 | 0.1711 | 6.378e-06 | 0.127 |
PCDHGA2__8 | 0.1711 | 6.378e-06 | 0.127 |
PCDHGA3__7 | 0.1711 | 6.378e-06 | 0.127 |
PCDHGA4__6 | 0.1711 | 6.378e-06 | 0.127 |
PCDHGA5__6 | 0.1711 | 6.378e-06 | 0.127 |
PCDHGA6__6 | 0.1711 | 6.378e-06 | 0.127 |
PCDHGA7__6 | 0.1711 | 6.378e-06 | 0.127 |
PATHOLOGY.N.STAGE | Mean (SD) | 0.82 (0.91) |
N | ||
0 | 305 | |
1 | 240 | |
2 | 87 | |
3 | 49 | |
Significant markers | N = 13 | |
pos. correlated | 8 | |
neg. correlated | 5 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
TCP11L1 | 0.1974 | 2.073e-07 | 0.00414 |
ADA | 0.1965 | 2.357e-07 | 0.00471 |
CEBPG | 0.1816 | 1.845e-06 | 0.0368 |
KIAA0182 | -0.1759 | 3.901e-06 | 0.0779 |
ATP2A2 | -0.1725 | 6.084e-06 | 0.121 |
ARHGEF3__1 | 0.1709 | 7.567e-06 | 0.151 |
SPATA12 | 0.1709 | 7.567e-06 | 0.151 |
SEPT8 | -0.1698 | 8.351e-06 | 0.167 |
LOC100286844 | -0.169 | 9.206e-06 | 0.184 |
TRIM31 | 0.1688 | 9.44e-06 | 0.188 |
PATHOLOGY.M.STAGE | Labels | N |
CM0 (I+) | 1 | |
M0 | 562 | |
M1 | 8 | |
MX | 119 | |
Significant markers | N = 541 |
GENDER | Labels | N |
FEMALE | 682 | |
MALE | 8 | |
Significant markers | N = 0 |
HISTOLOGICAL.TYPE | Labels | N |
INFILTRATING CARCINOMA NOS | 1 | |
INFILTRATING DUCTAL CARCINOMA | 473 | |
INFILTRATING LOBULAR CARCINOMA | 142 | |
MEDULLARY CARCINOMA | 5 | |
MIXED HISTOLOGY (PLEASE SPECIFY) | 24 | |
MUCINOUS CARCINOMA | 12 | |
OTHER SPECIFY | 32 | |
Significant markers | N = 1910 |
378 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N |
NO | 215 | |
YES | 475 | |
Significant markers | N = 378 | |
Higher in YES | 378 | |
Higher in NO | 0 |
W(pos if higher in 'YES') | wilcoxontestP | Q | AUC | |
---|---|---|---|---|
METAP2 | 68440 | 7.737e-13 | 1.55e-08 | 0.6702 |
C16ORF58 | 34127 | 2.88e-12 | 5.75e-08 | 0.6658 |
ZNF639 | 67831 | 4.692e-12 | 9.37e-08 | 0.6642 |
UHRF1BP1L | 67671 | 7.457e-12 | 1.49e-07 | 0.6626 |
HMG20B | 34484 | 8.13e-12 | 1.62e-07 | 0.6623 |
RAD50 | 67367 | 1.777e-11 | 3.55e-07 | 0.6597 |
NECAP1 | 67342 | 1.907e-11 | 3.81e-07 | 0.6594 |
USP34 | 67328 | 1.984e-11 | 3.96e-07 | 0.6593 |
MAEA | 35204 | 6.179e-11 | 1.23e-06 | 0.6553 |
ATG4B | 35264 | 7.288e-11 | 1.45e-06 | 0.6547 |
NUMBER.OF.LYMPH.NODES | Mean (SD) | 2.59 (4.8) |
Significant markers | N = 7 | |
pos. correlated | 3 | |
neg. correlated | 4 |
RACE | Labels | N |
AMERICAN INDIAN OR ALASKA NATIVE | 1 | |
ASIAN | 34 | |
BLACK OR AFRICAN AMERICAN | 112 | |
WHITE | 529 | |
Significant markers | N = 1574 |
ETHNICITY | Labels | N |
HISPANIC OR LATINO | 35 | |
NOT HISPANIC OR LATINO | 590 | |
Significant markers | N = 191 | |
Higher in NOT HISPANIC OR LATINO | 191 | |
Higher in HISPANIC OR LATINO | 0 |
W(pos if higher in 'NOT HISPANIC OR LATINO') | wilcoxontestP | Q | AUC | |
---|---|---|---|---|
LRRC66 | c("4153", "1.318e-08") | c("4153", "1.318e-08") | 0.000263 | 0.7898 |
WDFY3__1 | c("15992", "3.068e-08") | c("15992", "3.068e-08") | 0.000613 | 0.7784 |
ANAPC5 | c("15944", "4.628e-08") | c("15944", "4.628e-08") | 0.000924 | 0.7747 |
C3ORF17 | c("15732", "5.285e-08") | c("15732", "5.285e-08") | 0.00106 | 0.7736 |
NUP98 | c("15383", "6.116e-08") | c("15383", "6.116e-08") | 0.00122 | 0.7761 |
MRPL22 | c("15916", "6.228e-08") | c("15916", "6.228e-08") | 0.00124 | 0.7721 |
DPY19L1 | c("15935", "6.494e-08") | c("15935", "6.494e-08") | 0.0013 | 0.7717 |
C10ORF79 | c("15912", "7.346e-08") | c("15912", "7.346e-08") | 0.00147 | 0.7706 |
SCFD2 | c("15884", "7.398e-08") | c("15884", "7.398e-08") | 0.00148 | 0.7705 |
C4ORF33__1 | c("15906", "7.586e-08") | c("15906", "7.586e-08") | 0.00151 | 0.7703 |
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Expresson data file = BRCA-TP.meth.by_min_clin_corr.data.txt
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Clinical data file = BRCA-TP.merged_data.txt
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Number of patients = 690
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Number of genes = 19971
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Number of clinical features = 12
For survival clinical features, Wald's test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values using the 'coxph' function in R. Kaplan-Meier survival curves were plot using the four quartile subgroups of patients based on expression levels
For continuous numerical clinical features, Spearman's rank correlation coefficients (Spearman 1904) and two-tailed P values were estimated using 'cor.test' function in R
For multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' function in R
For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.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.
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.