This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.
Testing the association between 17315 genes and 5 clinical features across 506 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.
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1 gene correlated to 'Time to Death'.
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CDC73
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145 genes correlated to 'AGE'.
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KIF15 , MEX3C , EGR2 , LGALS8 , C10ORF35 , ...
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186 genes correlated to 'GENDER'.
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ALDOC , ZNF486 , CRIP1 , NMNAT3 , LOC400043 , ...
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242 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
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CCDC86 , TUBA4B , MAP1LC3B2 , TAF6 , HS1BP3 , ...
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433 genes correlated to 'NEOADJUVANT.THERAPY'.
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TAF6 , DKFZP779M0652 , HS1BP3 , SYNGR4 , RPS15 , ...
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=1 | shorter survival | N=0 | longer survival | N=1 |
AGE | Spearman correlation test | N=145 | older | N=131 | younger | N=14 |
GENDER | t test | N=186 | male | N=41 | female | N=145 |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=242 | yes | N=182 | no | N=60 |
NEOADJUVANT THERAPY | t test | N=433 | yes | N=326 | no | N=107 |
Time to Death | Duration (Months) | 0-223.4 (median=18.3) |
censored | N = 422 | |
death | N = 56 | |
Significant markers | N = 1 | |
associated with shorter survival | 0 | |
associated with longer survival | 1 |
HazardRatio | Wald_P | Q | C_index | |
---|---|---|---|---|
CDC73 | 0 | 2.414e-06 | 0.042 | 0.351 |
AGE | Mean (SD) | 57.47 (13) |
Significant markers | N = 145 | |
pos. correlated | 131 | |
neg. correlated | 14 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
KIF15 | 0.2973 | 9.117e-12 | 1.58e-07 |
MEX3C | 0.2874 | 4.627e-11 | 8.01e-07 |
EGR2 | 0.2856 | 6.172e-11 | 1.07e-06 |
LGALS8 | -0.2844 | 7.45e-11 | 1.29e-06 |
C10ORF35 | 0.2838 | 8.295e-11 | 1.44e-06 |
PAPSS1 | 0.2786 | 1.855e-10 | 3.21e-06 |
RPS2 | 0.2758 | 2.887e-10 | 5e-06 |
RPL13A | 0.2738 | 3.932e-10 | 6.81e-06 |
MTMR7 | 0.2731 | 4.344e-10 | 7.52e-06 |
RPL7A | 0.272 | 5.104e-10 | 8.83e-06 |
GENDER | Labels | N |
FEMALE | 500 | |
MALE | 6 | |
Significant markers | N = 186 | |
Higher in MALE | 41 | |
Higher in FEMALE | 145 |
T(pos if higher in 'MALE') | ttestP | Q | AUC | |
---|---|---|---|---|
ALDOC | -25.02 | 2.713e-89 | 4.7e-85 | 0.8637 |
ZNF486 | -18.01 | 3.185e-56 | 5.51e-52 | 0.819 |
CRIP1 | -16.27 | 3.944e-48 | 6.83e-44 | 0.8667 |
NMNAT3 | -13.04 | 2.914e-33 | 5.05e-29 | 0.687 |
LOC400043 | -12.99 | 7.319e-31 | 1.27e-26 | 0.6022 |
RND2 | -12.86 | 9.539e-28 | 1.65e-23 | 0.7923 |
EML1 | -11.17 | 7.152e-26 | 1.24e-21 | 0.6103 |
SPC25 | -11.85 | 1.759e-25 | 3.05e-21 | 0.7523 |
HSPC157 | -12.76 | 7.425e-25 | 1.29e-20 | 0.6363 |
ADCY5 | 12.08 | 2.017e-24 | 3.49e-20 | 0.7297 |
242 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N |
NO | 124 | |
YES | 382 | |
Significant markers | N = 242 | |
Higher in YES | 182 | |
Higher in NO | 60 |
T(pos if higher in 'YES') | ttestP | Q | AUC | |
---|---|---|---|---|
CCDC86 | 7.7 | 2.621e-13 | 4.54e-09 | 0.7089 |
TUBA4B | 7.29 | 1.756e-12 | 3.04e-08 | 0.6682 |
MAP1LC3B2 | -7.16 | 1.157e-11 | 2e-07 | 0.695 |
TAF6 | 7.05 | 1.256e-11 | 2.17e-07 | 0.6702 |
HS1BP3 | 7.02 | 1.372e-11 | 2.38e-07 | 0.6885 |
C12ORF52 | 7.04 | 1.413e-11 | 2.45e-07 | 0.6783 |
DDX54 | 7.04 | 1.413e-11 | 2.45e-07 | 0.6783 |
CCDC85B | 7.04 | 1.486e-11 | 2.57e-07 | 0.6834 |
MBD3 | 6.99 | 2.301e-11 | 3.98e-07 | 0.6819 |
SYNGR4 | 6.91 | 4.995e-11 | 8.64e-07 | 0.7098 |
NEOADJUVANT.THERAPY | Labels | N |
NO | 190 | |
YES | 316 | |
Significant markers | N = 433 | |
Higher in YES | 326 | |
Higher in NO | 107 |
T(pos if higher in 'YES') | ttestP | Q | AUC | |
---|---|---|---|---|
TAF6 | 8.94 | 7.834e-18 | 1.36e-13 | 0.7046 |
DKFZP779M0652 | 8.4 | 4.816e-16 | 8.34e-12 | 0.7038 |
HS1BP3 | 8.22 | 1.7e-15 | 2.94e-11 | 0.694 |
SYNGR4 | 8.26 | 1.861e-15 | 3.22e-11 | 0.7152 |
RPS15 | 8.2 | 2.066e-15 | 3.58e-11 | 0.7072 |
CATSPER2 | -8.33 | 2.624e-15 | 4.54e-11 | 0.7185 |
DLEU2L | -8.17 | 2.733e-15 | 4.73e-11 | 0.7058 |
C12ORF52 | 8.08 | 4.909e-15 | 8.5e-11 | 0.686 |
DDX54 | 8.08 | 4.909e-15 | 8.5e-11 | 0.686 |
MAP1LC3B2 | -8.13 | 5.013e-15 | 8.68e-11 | 0.7126 |
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Expresson data file = BRCA.meth.for_correlation.filtered_data.txt
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Clinical data file = BRCA.clin.merged.picked.txt
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Number of patients = 506
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Number of genes = 17315
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Number of clinical features = 5
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 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.
This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.