Inferring novel gene-disease associations using Medical Subject Heading Over-representation Profiles

Abstract 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