Journal
PLOS ONE
Volume 1, Issue 1, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0000061
Keywords
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Categories
Funding
- National Institutes of Health [GM61372, GM070789]
- National Science Foundation [0438291, 0121687, 0532231]
- Cure Autism Now Foundation
- Defense Advanced Research Projects Agency [FA8750-04-2-0123]
- [5-T15-LM007079]
- Direct For Computer & Info Scie & Enginr
- Div Of Information & Intelligent Systems [0121687] Funding Source: National Science Foundation
- Direct For Mathematical & Physical Scien
- Division Of Mathematical Sciences [0532231] Funding Source: National Science Foundation
- Div Of Information & Intelligent Systems
- Direct For Computer & Info Scie & Enginr [0438291] Funding Source: National Science Foundation
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Reliable and comprehensive maps of molecular pathways are indispensable for guiding complex biomedical experiments. Such maps are typically assembled from myriads of disparate research reports and are replete with inconsistencies due to variations in experimental conditions and/or errors. It is often an intractable task to manually verify internal consistency over a large collection of experimental statements. To automate large-scale reconciliation efforts, we propose a random-arcs-and-nodes model where both nodes (tissue-specific states of biological molecules) and arcs (interactions between them) are represented with random variables. We show how to obtain a non-contradictory model of a molecular network by computing the joint distribution for arc and node variables, and then apply our methodology to a realistic network, generating a set of experimentally testable hypotheses. This network, derived from an automated analysis of over 3,000 full-text research articles, includes genes that have been hypothetically linked to four neurological disorders: Alzheimer's disease, autism, bipolar disorder, and schizophrenia. We estimated that approximately 10% of the published molecular interactions are logically incompatible. Our approach can be directly applied to an array of diverse problems including those encountered in molecular biology, ecology, economics, politics, and sociology.
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