Correlation between mutation rate and clinical features
Kidney Chromophobe (Primary solid tumor)
17 October 2014 | analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C18051G4
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mutation rate and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C18051G4
Overview
Introduction

This pipeline uses various statistical tests to identify selected clinical features related to mutation rate.

Summary

Testing the association between 2 variables and 11 clinical features across 66 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 6 clinical features related to at least one variables.

- 2 variables correlated to 'AGE'.

- MUTATIONRATE_NONSYNONYMOUS , MUTATIONRATE_SILENT

- 1 variable correlated to 'AGE_mutation.rate'.

- MUTATIONRATE_NONSYNONYMOUS

- 2 variables correlated to 'NEOPLASM.DISEASESTAGE'.

- MUTATIONRATE_NONSYNONYMOUS , MUTATIONRATE_SILENT

- 2 variables correlated to 'PATHOLOGY.T.STAGE'.

- MUTATIONRATE_SILENT , MUTATIONRATE_NONSYNONYMOUS

- 2 variables correlated to 'PATHOLOGY.N.STAGE'.

- MUTATIONRATE_NONSYNONYMOUS , MUTATIONRATE_SILENT

- 1 variable correlated to 'ETHNICITY'.

- MUTATIONRATE_NONSYNONYMOUS

- No variables correlated to 'PATHOLOGY.M.STAGE', 'GENDER', 'KARNOFSKY.PERFORMANCE.SCORE', 'NUMBERPACKYEARSSMOKED', and 'RACE'.

Results
Overview of the results

Complete statistical result table is provided in Supplement Table 1

Table 1. Get Full Table This table shows the clinical features, statistical methods used, and the number of variables that are significantly associated with each clinical feature at P value < 0.05 and Q value < 0.3.

Clinical feature | Statistical test | Significant variables | Associated with |  | Associated with |
--- | --- | --- | --- | --- | --- | ---
AGE | Spearman correlation test | N=2 | older | N=2 | younger | N=0
AGE | Linear Regression Analysis | N=1 |  |  |  |
NEOPLASM DISEASESTAGE | Kruskal-Wallis test | N=2 |  |  |  |
PATHOLOGY T STAGE | Spearman correlation test | N=2 | higher stage | N=2 | lower stage | N=0
PATHOLOGY N STAGE | Spearman correlation test | N=2 | higher stage | N=2 | lower stage | N=0
PATHOLOGY M STAGE | Kruskal-Wallis test | N=0 |  |  |  |
GENDER | Wilcoxon test | N=0 |  |  |  |
KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=0 |  |  |  |
NUMBERPACKYEARSSMOKED | Spearman correlation test | N=0 |  |  |  |
RACE | Kruskal-Wallis test | N=0 |  |  |  |
ETHNICITY | Wilcoxon test | N=1 | not hispanic or latino | N=1 | hispanic or latino | N=0

Clinical variable #1: 'AGE'

2 variables related to 'AGE'.

Table S1. Basic characteristics of clinical feature: 'AGE'

AGE | Mean (SD) | 51.52 (14)
| Significant variables | N = 2
| pos. correlated | 2
| neg. correlated | 0

List of 2 variables associated with 'AGE'

Table S2. Get Full Table List of 2 variables significantly correlated to 'AGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
MUTATIONRATE_NONSYNONYMOUS | 0.4443 | 0.0001863 | 0.000373
MUTATIONRATE_SILENT | 0.3298 | 0.006846 | 0.00685

Clinical variable #2: 'AGE'

One variable related to 'AGE'.

Table S3. Basic characteristics of clinical feature: 'AGE'

AGE | Mean (SD) | 51.52 (14)
| Significant variables | N = 1

List of one variable associated with 'AGE'

Table S4. Get Full Table List of one variable significantly correlated to 'AGE' by Linear regression analysis [lm (mutation rate ~ age)]. Compared to a correlation analysis testing for interdependence of the variables, a regression model attempts to describe the dependence of a variable on one (or more) explanatory variables assuming that there is a one-way causal effect from the explanatory variable(s) to the response variable. If 'Residuals vs Fitted' plot (a standard residual plot) shows a random pattern indicating a good fit for a linear model, it explains linear regression relationship between Mutation rate and age factor. Adj.R-squared (= Explained variation / Total variation) indicates regression model's explanatory power.

| Adj.R.squared | F | P | Residual.std.err | DF | coef(intercept) | coef.p(intercept)
--- | --- | --- | --- | --- | --- | --- | ---
MUTATIONRATE_NONSYNONYMOUS | 0.0443 | 4.01 | 0.0494 | 2.47e-06 | 64 | 4.3e-08 ( -4.64e-07 ) | 0.0494 ( 0.687 )

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

2 variables related to 'NEOPLASM.DISEASESTAGE'.

Table S5. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE | Labels | N
| STAGE I | 21
| STAGE II | 25
| STAGE III | 14
| STAGE IV | 6
| Significant variables | N = 2

List of 2 variables associated with 'NEOPLASM.DISEASESTAGE'

Table S6. Get Full Table List of 2 variables differentially expressed by 'NEOPLASM.DISEASESTAGE'

| ANOVA_P | Q
--- | --- | ---
MUTATIONRATE_NONSYNONYMOUS | 0.02758 | 0.035
MUTATIONRATE_SILENT | 0.01748 | 0.035

Clinical variable #4: 'PATHOLOGY.T.STAGE'

2 variables related to 'PATHOLOGY.T.STAGE'.

Table S7. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE | Mean (SD) | 2.02 (0.85)
|  | N
| 1 | 21
| 2 | 25
| 3 | 18
| 4 | 2
| Significant variables | N = 2
| pos. correlated | 2
| neg. correlated | 0

List of 2 variables associated with 'PATHOLOGY.T.STAGE'

Table S8. Get Full Table List of 2 variables significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
MUTATIONRATE_SILENT | 0.3581 | 0.003157 | 0.00631
MUTATIONRATE_NONSYNONYMOUS | 0.2891 | 0.01856 | 0.0186

Clinical variable #5: 'PATHOLOGY.N.STAGE'

2 variables related to 'PATHOLOGY.N.STAGE'.

Table S9. Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE | Mean (SD) | 0.16 (0.47)
|  | N
| 0 | 40
| 1 | 3
| 2 | 2
| Significant variables | N = 2
| pos. correlated | 2
| neg. correlated | 0

List of 2 variables associated with 'PATHOLOGY.N.STAGE'

Table S10. Get Full Table List of 2 variables significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
MUTATIONRATE_NONSYNONYMOUS | 0.4184 | 0.004231 | 0.00846
MUTATIONRATE_SILENT | 0.354 | 0.01703 | 0.017

Clinical variable #6: 'PATHOLOGY.M.STAGE'

No variable related to 'PATHOLOGY.M.STAGE'.

Table S11. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE | Labels | N
| M0 | 34
| M1 | 2
| MX | 9
| Significant variables | N = 0

Clinical variable #7: 'GENDER'

No variable related to 'GENDER'.

Table S12. Basic characteristics of clinical feature: 'GENDER'

GENDER | Labels | N
| FEMALE | 27
| MALE | 39
| Significant variables | N = 0

Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

No variable related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S13. Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE | Mean (SD) | 89.09 (9.4)
| Score | N
| 70 | 1
| 80 | 2
| 90 | 5
| 100 | 3
| Significant variables | N = 0

Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No variable related to 'NUMBERPACKYEARSSMOKED'.

Table S14. Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED | Mean (SD) | 25.09 (22)
| Significant variables | N = 0

Clinical variable #10: 'RACE'

No variable related to 'RACE'.

Table S15. Basic characteristics of clinical feature: 'RACE'

RACE | Labels | N
| ASIAN | 2
| BLACK OR AFRICAN AMERICAN | 4
| WHITE | 58
| Significant variables | N = 0

Clinical variable #11: 'ETHNICITY'

One variable related to 'ETHNICITY'.

Table S16. Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY | Labels | N
| HISPANIC OR LATINO | 4
| NOT HISPANIC OR LATINO | 32
| Significant variables | N = 1
| Higher in NOT HISPANIC OR LATINO | 1
| Higher in HISPANIC OR LATINO | 0

List of one variable associated with 'ETHNICITY'

Table S17. Get Full Table List of one variable differentially expressed by 'ETHNICITY'

| W(pos if higher in 'NOT HISPANIC OR LATINO') | wilcoxontestP | Q | AUC
--- | --- | --- | --- | ---
MUTATIONRATE_NONSYNONYMOUS | c("105", "0.04149") | c("105", "0.04149") | 0.083 | 0.8203

Methods & Data
Input

- Expresson data file = KICH-TP.patients.counts_and_rates.txt

- Clinical data file = KICH-TP.merged_data.txt

- Number of patients = 66

- Number of variables = 2

- Number of clinical features = 11

Correlation analysis

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

ANOVA analysis

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

Student's t-test analysis

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

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.

Download Results

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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

References
[1] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[2] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[3] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[4] 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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