Acute Myeloid Leukemia: Correlation between gene methylation status and clinical features

Maintained by Juok Cho (Broad Institute)

Overview

Introduction

This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.

Summary

Testing the association between 20239 genes and 3 clinical features across 192 samples, statistically thresholded by Q value < 0.05, 2 clinical features related to at least one genes.

35 genes correlated to 'AGE'.

ETV1 , KIAA1377 , ANGPTL5 , AASS , TMEM20 , ...

7 genes correlated to 'GENDER'.

AP2B1 , KIF4B , DKFZP434L187 , MYO5A , DACH1 , ...

No genes correlated to 'Time to Death'

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 genes that are significantly associated with each clinical feature at Q value < 0.05.

Clinical feature	Statistical test	Significant genes	Associated with		Associated with
Time to Death	Cox regression test	N=0
AGE	Spearman correlation test	N=35	older	N=3	younger	N=32
GENDER	t test	N=7	male	N=3	female	N=4

Clinical variable #1: 'Time to Death'

No gene related to 'Time to Death'.

Table S1. Basic characteristics of clinical feature: 'Time to Death'


Time to Death	Duration (Months)	0.9-94.1 (median=12)
	censored	N = 63
	death	N = 103

	Significant markers	N = 0

Clinical variable #2: 'AGE'

35 genes related to 'AGE'.

Table S2. Basic characteristics of clinical feature: 'AGE'


AGE	Mean (SD)	55.13 (16)
	Significant markers	N = 35
	pos. correlated	3
	neg. correlated	32

List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3. Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
ETV1	-0.4366	2.447e-10	4.95e-06
KIAA1377	-0.4313	4.213e-10	8.53e-06
ANGPTL5	-0.4298	4.946e-10	1e-05
AASS	-0.4264	6.957e-10	1.41e-05
TMEM20	-0.4239	8.951e-10	1.81e-05
MYEF2	-0.3908	2.089e-08	0.000423
HCG4	-0.3887	2.528e-08	0.000511
HOOK1	-0.3841	3.794e-08	0.000768
TBC1D12	-0.3797	5.58e-08	0.00113
ENPP5	-0.3673	1.598e-07	0.00323

Figure S1. Get High-res Image As an example, this figure shows the association of ETV1 to 'AGE'. P value = 2.45e-10 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

7 genes related to 'GENDER'.

Table S4. Basic characteristics of clinical feature: 'GENDER'


GENDER	Labels	N
	FEMALE	89
	MALE	103

	Significant markers	N = 7
	Higher in MALE	3
	Higher in FEMALE	4

List of 7 genes differentially expressed by 'GENDER'

Table S5. Get Full Table List of 7 genes differentially expressed by 'GENDER'

	T(pos if higher in 'MALE')	ttestP	Q	AUC
AP2B1	-11.96	9.237e-24	1.87e-19	0.9023
KIF4B	-10.61	5.859e-21	1.19e-16	0.8587
DKFZP434L187	9.15	1.114e-16	2.25e-12	0.86
MYO5A	-6.88	1.117e-10	2.26e-06	0.8276
DACH1	5.78	3.086e-08	0.000624	0.734
RNASEH2C	5.66	7.663e-08	0.00155	0.8014
LOC100240735	-5.17	5.978e-07	0.0121	0.7071

Figure S2. Get High-res Image As an example, this figure shows the association of AP2B1 to 'GENDER'. P value = 9.24e-24 with T-test analysis.

Methods & Data

Input

Expresson data file = LAML.meth.for_correlation.filtered_data.txt
Clinical data file = LAML.clin.merged.picked.txt
Number of patients = 192
Number of genes = 20239
Number of clinical features = 3

Survival analysis

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

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

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

References

[1] Andersen and Gill, Cox's regression model for counting processes, a large sample study, Annals of Statistics 10(4):1100-1120 (1982)

[2] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)

[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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