RITAN: Rapid integration of term annotation and network resources

Background: Identifying the biologic functions of groups of genes identified in high-throughput studies currently requires considerable time and/or bioinformatics experience. This is due in part to each resource housed within separate databases, requiring users to know about them, and integrate across them. Time consuming and often repeated for each study, integrating across resources and merging with data under study is an increasingly common bioinformatics task. Methods: We developed an open-source R software package for assisting researchers in annotating their genesets with functions, pathways, and their interconnectivity across a diversity of network resources. Results: We present rapid integration of term annotation and network resources (RITAN) for the rapid and comprehensive annotation of a list of genes using functional term and pathway resources and their relationships among each other using multiple network biology resources. Currently, and to comply with data redistribution policies, RITAN allows rapid access to 16 term annotations spanning gene ontology, biologic pathways, and immunologic modules, and nine network biology resources, with support for user-supplied resources; we provide recommendations for additional resources and scripts to facilitate their addition to RITAN. Having the resources together in the same system allows users to derive novel combinations. RITAN has a growing set of tools to explore the relationships within resources themselves. These tools allow users to merge resources together such that the merged annotations have a minimal overlap with one another. Because we index both function annotation and network interactions, the combination allows users to expand small groups of genes using links from biologic networks-either by adding all neighboring genes or by identifying genes that efficiently connect among input genes-followed by term enrichment to identify functions. That is, users can start from a core set of genes, identify interacting genes from biologic networks, and then identify the functions to which the expanded list of genes contribute. Conclusion: We believe RITAN fills the important niche of bridging the results of high-throughput experiments with the ever-growing corpus of functional annotations and network biology resources. Availability: Rapid integration of term annotation and network resources is available as an R package at github.com/MTZimmer/RITAN and BioConductor.org.