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Tissue-aware data integration approach for the inference of pathway interactions in metazoan organisms.


ABSTRACT: Leveraging the large compendium of genomic data to predict biomedical pathways and specific mechanisms of protein interactions genome-wide in metazoan organisms has been challenging. In contrast to unicellular organisms, biological and technical variation originating from diverse tissues and cell-lineages is often the largest source of variation in metazoan data compendia. Therefore, a new computational strategy accounting for the tissue heterogeneity in the functional genomic data is needed to accurately translate the vast amount of human genomic data into specific interaction-level hypotheses.We developed an integrated, scalable strategy for inferring multiple human gene interaction types that takes advantage of data from diverse tissue and cell-lineage origins. Our approach specifically predicts both the presence of a functional association and also the most likely interaction type among human genes or its protein products on a whole-genome scale. We demonstrate that directly incorporating tissue contextual information improves the accuracy of our predictions, and further, that such genome-wide results can be used to significantly refine regulatory interactions from primary experimental datasets (e.g. ChIP-Seq, mass spectrometry).An interactive website hosting all of our interaction predictions is publically available at http://pathwaynet.princeton.edu. Software was implemented using the open-source Sleipnir library, which is available for download at https://bitbucket.org/libsleipnir/libsleipnir.bitbucket.org.Supplementary data are available at Bioinformatics online.

SUBMITTER: Park CY 

PROVIDER: S-EPMC4804827 | biostudies-other | 2015 Apr

REPOSITORIES: biostudies-other

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Tissue-aware data integration approach for the inference of pathway interactions in metazoan organisms.

Park Christopher Y CY   Krishnan Arjun A   Zhu Qian Q   Wong Aaron K AK   Lee Young-Suk YS   Troyanskaya Olga G OG  

Bioinformatics (Oxford, England) 20141126 7


<h4>Motivation</h4>Leveraging the large compendium of genomic data to predict biomedical pathways and specific mechanisms of protein interactions genome-wide in metazoan organisms has been challenging. In contrast to unicellular organisms, biological and technical variation originating from diverse tissues and cell-lineages is often the largest source of variation in metazoan data compendia. Therefore, a new computational strategy accounting for the tissue heterogeneity in the functional genomic  ...[more]

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