Abstract

Motivation: New relationships are often implicit from existing information, but the amount and growth of published literature limits the scope of analysis an individual can accomplish. Our goal was to develop and test a computational method to identify relationships within scientific reports, such that large sets of relationships between unrelated items could be sought out and statistically ranked for their potential relevance as a set.

Results: We first construct a network of tentative relationships between ‘objects’ of biomedical research interest (e.g. genes, diseases, phenotypes, chemicals) by identifying their co-occurrences within all electronically available MEDLINE records. Relationships shared by two unrelated objects are then ranked against a random network model to estimate the statistical significance of any given grouping. When compared against known relationships, we find that this ranking correlates with both the probability and frequency of object co-occurrence, demonstrating the method is well suited to discover novel relationships based upon existing shared relationships. To test this, we identified compounds whose shared relationships predicted they might affect the development and/or progression of cardiac hypertrophy. When laboratory tests were performed in a rodent model, chlorpromazine was found to reduce the progression of cardiac hypertrophy.

Supplementary information:http://innovation.swmed.edu/IRIDESCENT/Supplemental_Info.htm

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Author notes

1Advanced Center for Genome Technology, Department of Botany and Microbiology, The University of Oklahoma, 620 Parrington Oval Rm. 106, Norman, OK 73019, USA, 2Department of Internal Medicine, 3Division of Cardiology and 4McDermott Center for Human Growth and Development, Department of Biochemistry, Center for Biomedical Inventions, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA

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