Pathway databases: making chemical and biological sense of the genomic data flood

Pathway databases are a means to systematically associate proteins with their functions and link them into networks that describe the reaction space of an organism. Here, the Reactome Knowledgebase provides a convenient example to illustrate strategies used to assemble such a reaction space based on manually curated experimental data, approaches to semiautomated extension of these manual annotations to infer annotations for a large fraction of a species' proteins, and the use of networks of functional annotations to infer pathway relationships among variant proteins that have been associated with disease risk through genome-wide surveys and resequencing studies of tumors.