ranking transitive chemical-disease inferences using local network topology in the comparative toxicogenomics database排名传递chemical-disease推断比较toxicogenomics数据库中使用本地网络拓扑.pdfVIP

Ranking Transitive Chemical-Disease Inferences Using Local Network Topology in the Comparative Toxicogenomics Database 1 2 1 2 2 Benjamin L. King , Allan Peter Davis , Michael C. Rosenstein , Thomas C. Wiegers , Carolyn J. Mattingly * 1 Mount Desert Island Biological Laboratory, Salisbury Cove, Maine, United States of America, 2 North Carolina State University, Raleigh, North Carolina, United States of America Abstract Exposure to chemicals in the environment is believed to play a critical role in the etiology of many human diseases. To enhance understanding about environmental effects on human health, the Comparative Toxicogenomics Database (CTD; ) provides unique curated data that enable development of novel hypotheses about the relationships between chemicals and diseases. CTD biocurators read the literature and curate direct relationships between chemicals- genes, genes-diseases, and chemicals-diseases. These direct relationships are then computationally integrated to create additional inferred relationships; for example, a direct chemical-gene statement can be combined with a direct gene-disease statement to generate a chemical-disease inference (inferred via the shared gene). In CTD, the number of inferences has increased exponentially as the number of direct chemical, gene and disease interactions has grown. To help users navigate and prioritize these inferences for hypothesis development, we implemented a statistic to score and rank them based on the topology of the local network consisting of the chemical, disease and each of the genes used to make an inference. In this network, chemicals, diseases and genes are nodes connected by edges representing the curated interactions. Like other biological n