Statistical modeling of biomedical corpora: mining the Caenorhabditis Genetic Center Bibliography for genes related to life span

Journal Article · Mon May 08 00:00:00 EDT 2006 · BMC Bioinformatics

DOI:https://doi.org/10.1186/1471-2105-7-250· OSTI ID:1626320

Blei, D. M. ^[1]; Franks, K. ^[2]; Jordan, M. I. ^[3]; Mian, I. S. ^[2]

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1. Princeton Univ., NJ (United States). Computer Science Dept.; DOE/OSTI
2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
3. Univ. of California, Berkeley, CA (United States). Dept. of Statistics; Univ. of California, Berkeley, CA (United States). Dept. of EECS

Background: The statistical modeling of biomedical corpora could yield integrated, coarse-to-fine views of biological phenomena that complement discoveries made from analysis of molecular sequence and profiling data. Here, the potential of such modeling is demonstrated by examining the 5,225 free-text items in the Caenorhabditis Genetic Center (CGC) Bibliography using techniques from statistical information retrieval. Items in the CGC biomedical text corpus were modeled using the Latent Dirichlet Allocation (LDA) model. LDA is a hierarchical Bayesian model which represents a document as a random mixture over latent topics; each topic is characterized by a distribution over words. Results: An LDA model estimated from CGC items had better predictive performance than two standard models (unigram and mixture of unigrams) trained using the same data. To illustrate the practical utility of LDA models of biomedical corpora, a trained CGC LDA model was used for a retrospective study of nematode genes known to be associated with life span modification. Corpus- , document-, and word-level LDA parameters were combined with terms from the Gene Ontology to enhance the explanatory value of the CGC LDA model, and to suggest additional candidates for age-related genes. A novel, pairwise document similarity measure based on the posterior distribution on the topic simplex was formulated and used to search the CGC database for "homologs" of a "query" document discussing the life span-modifying clk-2 gene. Inspection of these document homologs enabled and facilitated the production of hypotheses about the function and role of clk-2. Conclusion: Like other graphical models for genetic, genomic and other types of biological data, LDA provides a method for extracting unanticipated insights and generating predictions amenable to subsequent experimental validation.

• Research Organization: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
• Grant/Contract Number: AC02-05CH11231
• OSTI ID: 1626320
• Journal Information: BMC Bioinformatics, Journal Name: BMC Bioinformatics Journal Issue: 1 Vol. 7; ISSN 1471-2105
• Publisher: BioMed Central
• Country of Publication: United States
• Language: English

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