Abstract
BackgroundPathway-oriented experimental and computational studies have led to a significant accumulation of biological knowledge concerning three major types of biological pathway events: molecular signaling events, gene regulation events, and metabolic reaction events. A pathway consists of a series of molecular pathway events that link molecular entities such as proteins, genes, and metabolites. There are approximately 300 biological pathway resources as of April 2009 according to the Pathguide database; however, these pathway databases generally have poor coverage or poor quality, and are difficult to integrate, due to syntactic-level and semantic-level data incompatibilities.ResultsWe developed the Human Pathway Database (HPD) by integrating heterogeneous human pathway data that are either curated at the NCI Pathway Interaction Database (PID), Reactome, BioCarta, KEGG or indexed from the Protein Lounge Web sites. Integration of pathway data at syntactic, semantic, and schematic levels was based on a unified pathway data model and data warehousing-based integration techniques. HPD provides a comprehensive online view that connects human proteins, genes, RNA transcripts, enzymes, signaling events, metabolic reaction events, and gene regulatory events. At the time of this writing HPD includes 999 human pathways and more than 59,341 human molecular entities. The HPD software provides both a user-friendly Web interface for online use and a robust relational database backend for advanced pathway querying. This pathway tool enables users to 1) search for human pathways from different resources by simply entering genes/proteins involved in pathways or words appearing in pathway names, 2) analyze pathway-protein association, 3) study pathway-pathway similarity, and 4) build integrated pathway networks. We demonstrated the usage and characteristics of the new HPD through three breast cancer case studies.ConclusionHPD http://bio.informatics.iupui.edu/HPD is a new resource for searching, managing, and studying human biological pathways. Users of HPD can search against large collections of human biological pathways, compare related pathways and their molecular entity compositions, and build high-quality, expanded-scope disease pathway models. The current HPD software can help users address a wide range of pathway-related questions in human disease biology studies.
Highlights
Pathway-oriented experimental and computational studies have led to a significant accumulation of biological knowledge concerning three major types of biological pathway events: molecular signaling events, gene regulation events, and metabolic reaction events
Users of Human Pathway Database (HPD) can search against large collections of human biological pathways, compare related pathways and their molecular entity compositions, and build high-quality, expanded-scope disease pathway models
The current HPD software can help users address a wide range of pathway-related questions in human disease biology studies
Summary
Pathway-oriented experimental and computational studies have led to a significant accumulation of biological knowledge concerning three major types of biological pathway events: molecular signaling events, gene regulation events, and metabolic reaction events. A pathway consists of a series of molecular pathway events that link molecular entities such as proteins, genes, and metabolites. While the precise definition of "biological pathway" is still debatable, most researchers regard a biological pathway as a series of interconnected cellular events among biomolecular entities. There are three major types of molecular pathway events (or, events for brevity) that define biological pathways:. Common in signalling pathways (e.g., Wnt signaling pathway [2]), these events define the interactions among molecular entities during signal transduction cascades, i.e., how external stimuli such as molecules in the cellular environment are transduced into intracellular molecular signals that are relayed among different cellular organelles. Examples of signal transduction events in signalling pathways are protein-protein interactions, protein post-translational modifications, protein translocations, and protein complex formations/dissociations
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