Markov chain Monte Carlo for active module identification problem
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RESEARCH
Open Access
Markov chain Monte Carlo for active module identification problem Nikita Alexeev1 † , Javlon Isomurodov1,2† , Vladimir Sukhov1,2 , Gennady Korotkevich1 and Alexey Sergushichev1* From 15th International Symposium on Bioinformatics Research and Applications (ISBRA’19) Barcelona, Spain. 3-6 June 2019 *Correspondence: [email protected] † Nikita Alexeev and Javlon Isomurodov contributed equally to this work. 1 Computer Technologies Laboratory, ITMO University, Saint Petersburg, Russia Full list of author information is available at the end of the article
Abstract Background: Integrative network methods are commonly used for interpretation of high-throughput experimental biological data: transcriptomics, proteomics, metabolomics and others. One of the common approaches is finding a connected subnetwork of a global interaction network that best encompasses significant individual changes in the data and represents a so-called active module. Usually methods implementing this approach find a single subnetwork and thus solve a hard classification problem for vertices. This subnetwork inherently contains erroneous vertices, while no instrument is provided to estimate the confidence level of any particular vertex inclusion. To address this issue, in the current study we consider the active module problem as a soft classification problem. Results: We propose a method to estimate probabilities of each vertex to belong to the active module based on Markov chain Monte Carlo (MCMC) subnetwork sampling. As an example of the performance of our method on real data, we run it on two gene expression datasets. For the first many-replicate expression dataset we show that the proposed approach is consistent with an existing resampling-based method. On the second dataset the jackknife resampling method is inapplicable due to the small number of biological replicates, but the MCMC method can be run and shows high classification performance. Conclusions: The proposed method allows to estimate the probability that an individual vertex belongs to the active module as well as the false discovery rate (FDR) for a given set of vertices. Given the estimated probabilities, it becomes possible to provide a connected subgraph in a consistent manner for any given FDR level: no (Continued on next page)
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