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Inferring novel gene-disease associations using Medical Subject Heading Over-representation Profiles
Warren A Cheung1, Bf Francis Ouellette2, Wyeth W Wasserman3
1Bioinformatics Graduate Program, Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, 980 W. 28th Ave, Vancouver, V5Z 4H4, Canada.
Background:
MEDLINE(®)/PubMed(®) currently indexes over 18 million biomedical articles, providing unprecedented opportunities and challenges for text analysis. Using Medical Subject Heading Over-representation Profiles (MeSHOPs), an entity of interest can be robustly summarized, quantitatively identifying associated biomedical terms and predicting novel indirect associations.
Methods:
A procedure is introduced for quantitative comparison of MeSHOPs derived from a group of MEDLINE(®) articles for a biomedical topic (for example, articles for a specific gene or disease). Similarity scores are computed to compare MeSHOPs of genes and diseases.
Results:
Similarity scores successfully infer novel associations between diseases and genes. The number of papers addressing a gene or disease has a strong influence on predicted associations, revealing an important bias for gene-disease relationship prediction. Predictions derived from comparisons of MeSHOPs achieves a mean 8% AUC improvement in the identification of gene-disease relationships compared to gene-independent baseline properties.
Conclusions:
MeSHOP comparisons are demonstrated to provide predictive capacity for novel relationships between genes and human diseases. We demonstrate the impact of literature bias on the performance of gene-disease prediction methods. MeSHOPs provide a rich source of annotation to facilitate relationship discovery in biomedical informatics.
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