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Berchtold, Evi; Csaba, Gergely and Zimmer, Ralf (2017): RelExplain-integrating data and networks to explain biological processes. In: Bioinformatics, Vol. 33, No. 12: pp. 1837-1844

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Motivation: The goal of many genome-wide experiments is to explain the changes between the analyzed conditions. Typically, the analysis is started with a set of differential genes DG and the first step is to identify the set of relevant biological processes BP. Current enrichment methods identify the involved biological process via statistically significant overrepresentation of differential genes in predefined sets, but do not further explain how the differential genes interact with each other or which other genes might be important for the enriched process. Other network-based methods determine subnetworks of interacting genes containing many differential genes, but do not employ process knowledge for a more focused analysis. Results: RelExplain is a method to analyze a given biological process bp (e.g. identified by enrichment) in more detail by computing an explanation using the measured DG and a given network. An explanation is a subnetwork that contains the differential genes in the process bp and connects them in the best way given the experimental data using also genes that are not differential or not in bp. RelExplain takes into account the functional annotations of nodes and the edge consistency of the measurements. Explanations are compact networks of the relevant part of the bp and additional nodes that might be important for the bp. Our evaluation showed that RelExplain is better suited to retrieve manually curated subnetworks from unspecific networks than other algorithms. The interactive RelExplain tool allows to compute and inspect sub-optimal and alternative optimal explanations.

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