Discovering Networks of Perturbed Biological Processes in Hepatocyte Cultures

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dc.contributor.authorLasher, Christopher D.en
dc.contributor.authorRajagopalan, Padmavathyen
dc.contributor.authorMurali, T. M.en
dc.contributor.departmentChemical Engineeringen
dc.contributor.departmentComputer Scienceen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.contributor.departmentInstitute for Critical Technology and Applied Science (ICTAS)en
dc.date.accessioned2018-11-08T15:08:07Zen
dc.date.available2018-11-08T15:08:07Zen
dc.date.issued2011-01-05en
dc.description.abstractThe liver plays a vital role in glucose homeostasis, the synthesis of bile acids and the detoxification of foreign substances. Liver culture systems are widely used to test adverse effects of drugs and environmental toxicants. The two most prevalent liver culture systems are hepatocyte monolayers (HMs) and collagen sandwiches (CS). Despite their wide use, comprehensive transcriptional programs and interaction networks in these culture systems have not been systematically investigated. We integrated an existing temporal transcriptional dataset for HM and CS cultures of rat hepatocytes with a functional interaction network of rat genes. We aimed to exploit the functional interactions to identify statistically significant linkages between perturbed biological processes. To this end, we developed a novel approach to compute Contextual Biological Process Linkage Networks (CBPLNs). CBPLNs revealed numerous meaningful connections between different biological processes and gene sets, which we were successful in interpreting within the context of liver metabolism. Multiple phenomena captured by CBPLNs at the process level such as regulation, downstream effects, and feedback loops have well described counterparts at the gene and protein level. CBPLNs reveal high-level linkages between pathways and processes, making the identification of important biological trends more tractable than through interactions between individual genes and molecules alone. Our approach may provide a new route to explore, analyze, and understand cellular responses to internal and external cues within the context of the intricate networks of molecular interactions that control cellular behavior.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0015247en
dc.identifier.eissn1932-6203en
dc.identifier.issue1en
dc.identifier.othere15247en
dc.identifier.pmid21245926en
dc.identifier.urihttp://hdl.handle.net/10919/85802en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleDiscovering Networks of Perturbed Biological Processes in Hepatocyte Culturesen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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