Guidance for RNA-seq co-expression network construction and analysis: safety in numbers

Ballouz, S., Verleyen, W., Gillis, J. (February 2015) Guidance for RNA-seq co-expression network construction and analysis: safety in numbers. Bioinformatics. ISSN 1367-4803

DOI: 10.1093/bioinformatics/btv118


MOTIVATION: RNA-seq co-expression analysis is in its infancy and reasonable practices remain poorly defined. We assessed a variety of RNA-seq expression data to determine factors affecting functional connectivity and topology in co-expression networks. RESULTS: We examine RNA-seq co-expression data generated from 1,970 RNA-seq samples using a guilt-by-association framework, in which genes are assessed for the tendency of co-expression to reflect shared function. Minimal experimental criteria to obtain performance on par with microarrays were >20 samples with read depth >10M per sample. While the aggregate network constructed shows good performance (AUROC~0.71), the dependency on number of experiments used is nearly identical to that present in microarrays, suggesting thousands of samples to obtain 'gold-standard' co-expression. We find a major topological difference between RNA-seq and microarray co-expression in the form of low overlaps between hub-like genes from each network due to changes in the correlation of expression noise within each technology. Supplementary information: Networks are available at: and supplementary data are available at Bioinformatics online. CONTACT:

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics
Investigative techniques and equipment > assays > RNA-seq
CSHL Authors:
Communities: CSHL labs > Gillis Lab
Stanley Institute for Cognitive Genomics
Depositing User: Matt Covey
Date: 24 February 2015
Date Deposited: 06 Mar 2015 20:48
Last Modified: 06 Nov 2015 20:05
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