Coexpression network based on natural variation in human gene expression reveals gene interactions and functions
- 1 Medical Scientist Training Program, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
- 2 Department of Computer and Information Science, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
- 3 Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
- 4 Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
- 5 Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Abstract
Genes interact in networks to orchestrate cellular processes. Analysis of these networks provides insights into gene interactions and functions. Here, we took advantage of normal variation in human gene expression to infer gene networks, which we constructed using correlations in expression levels of more than 8.5 million gene pairs in immortalized B cells from three independent samples. The resulting networks allowed us to identify biological processes and gene functions. Among the biological pathways, we found processes such as translation and glycolysis that co-occur in the same subnetworks. We predicted the functions of poorly characterized genes, including CHCHD2 and TMEM111, and provided experimental evidence that TMEM111 is part of the endoplasmic reticulum-associated secretory pathway. We also found that IFIH1, a susceptibility gene of type 1 diabetes, interacts with YES1, which plays a role in glucose transport. Furthermore, genes that predispose to the same diseases are clustered nonrandomly in the coexpression network, suggesting that networks can provide candidate genes that influence disease susceptibility. Therefore, our analysis of gene coexpression networks offers information on the role of human genes in normal and disease processes.
Footnotes
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↵6 Richard S. Spielman passed away suddenly in April 2009 during the preparation of this article.
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↵7 Corresponding author.
E-mail vcheung{at}mail.med.upenn.edu; fax (267) 426-9734.
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[Supplemental material is available online at http://www.genome.org. Our data and the resulting networks are available at http://www.geneticsofgeneexpression.org/network/. Microarray data from this study have been submitted to Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under accession no. GSE12526.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.097600.109.
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- Received June 19, 2009.
- Accepted August 13, 2009.
- Copyright © 2009 by Cold Spring Harbor Laboratory Press
