COSINE: COndition-SpecIfic sub-NEtwork identification using a global optimization method

MOTIVATION The identification of condition specific sub-networks from gene expression profiles has important biological applications, ranging from the selection of disease-related biomarkers to the discovery of pathway alterations across different phenotypes. Although many methods exist for extracting these sub-networks, very few existing approaches simultaneously consider both the differential expression of individual genes and the differential correlation of gene pairs, losing potentially valuable information in the data. RESULTS In this article, we propose a new method, COSINE (COndition SpecIfic sub-NEtwork), which employs a scoring function that jointly measures the condition-specific changes of both 'nodes' (individual genes) and 'edges' (gene-gene co-expression). It uses the genetic algorithm to search for the single optimal sub-network which maximizes the scoring function. We applied COSINE to both simulated datasets with various differential expression patterns, and three real datasets, one prostate cancer dataset, a second one from the across-tissue comparison of morbidly obese patients and the other from the across-population comparison of the HapMap samples. Compared with previous methods, COSINE is more powerful in identifying truly significant sub-networks of appropriate size and meaningful biological relevance. AVAILABILITY The R code is available as the COSINE package on CRAN: http://cran.r-project.org/web/packages/COSINE/index.html.