Correlation between miRseq expression and clinical features

Acute Myeloid Leukemia (Primary blood derived cancer - Peripheral blood)

23 May 2013 | analyses__2013_05_23

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between miRseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C14F1NSB

Overview

Introduction

This pipeline uses various statistical tests to identify miRs whose expression levels correlated to selected clinical features.

Summary

Testing the association between 354 genes and 3 clinical features across 188 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

7 genes correlated to 'Time to Death'.

HSA-MIR-362 , HSA-MIR-532 , HSA-MIR-181B-1 , HSA-MIR-502 , HSA-MIR-660 , ...

5 genes correlated to 'AGE'.

HSA-MIR-598 , HSA-MIR-766 , HSA-MIR-29B-1 , HSA-MIR-20B , HSA-MIR-363

3 genes correlated to 'GENDER'.

HSA-MIR-107 , HSA-MIR-1226 , HSA-MIR-505

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=7	shorter survival	N=6	longer survival	N=1
AGE	Spearman correlation test	N=5	older	N=4	younger	N=1
GENDER	t test	N=3	male	N=3	female	N=0

Clinical variable #1: 'Time to Death'

7 genes 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 = 62
	death	N = 100

	Significant markers	N = 7
	associated with shorter survival	6
	associated with longer survival	1

List of 7 genes significantly associated with 'Time to Death' by Cox regression test

Table S2. Get Full Table List of 7 genes significantly associated with 'Time to Death' by Cox regression test

	HazardRatio	Wald_P	Q	C_index
HSA-MIR-362	1.51	2.917e-06	0.001	0.669
HSA-MIR-532	1.48	9.616e-06	0.0034	0.668
HSA-MIR-181B-1	0.77	8.478e-05	0.03	0.378
HSA-MIR-502	1.43	8.721e-05	0.031	0.644
HSA-MIR-660	1.43	9.931e-05	0.035	0.643
HSA-MIR-501	1.33	0.000109	0.038	0.641
HSA-MIR-188	1.38	0.0001184	0.041	0.635

Figure S1. Get High-res Image As an example, this figure shows the association of HSA-MIR-362 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 2.92e-06 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

5 genes related to 'AGE'.

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


AGE	Mean (SD)	54.89 (16)
	Significant markers	N = 5
	pos. correlated	4
	neg. correlated	1

List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

Table S4. Get Full Table List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
HSA-MIR-598	0.3159	1.653e-05	0.00585
HSA-MIR-766	-0.2945	4.1e-05	0.0145
HSA-MIR-29B-1	0.2923	4.689e-05	0.0165
HSA-MIR-20B	0.2895	5.577e-05	0.0196
HSA-MIR-363	0.2772	0.0001175	0.0411

Figure S2. Get High-res Image As an example, this figure shows the association of HSA-MIR-598 to 'AGE'. P value = 1.65e-05 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

3 genes related to 'GENDER'.

Table S5. Basic characteristics of clinical feature: 'GENDER'


GENDER	Labels	N
	FEMALE	87
	MALE	101

	Significant markers	N = 3
	Higher in MALE	3
	Higher in FEMALE	0

List of 3 genes differentially expressed by 'GENDER'

Table S6. Get Full Table List of 3 genes differentially expressed by 'GENDER'

	T(pos if higher in 'MALE')	ttestP	Q	AUC
HSA-MIR-107	4.15	5.109e-05	0.0181	0.6711
HSA-MIR-1226	4.03	8.43e-05	0.0298	0.6651
HSA-MIR-505	4.02	8.681e-05	0.0306	0.6749

Figure S3. Get High-res Image As an example, this figure shows the association of HSA-MIR-107 to 'GENDER'. P value = 5.11e-05 with T-test analysis.

Methods & Data

Input

Expresson data file = LAML-TB.miRseq_RPKM_log2.txt
Clinical data file = LAML-TB.clin.merged.picked.txt
Number of patients = 188
Number of genes = 354
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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