NetPath: A Public Resource of Curated Signal Transduction Pathways - Development of an initial set of immune signaling pathways

¹Rajesh Raju, ¹S Sujatha Mohan, ^1,3Balamurugan Periaswamy, ^1,3Suresh Mathivanan, ¹Kumaran Kandasamy, ¹Shivakumar Keerthikumar, ¹Shubha Suresh, ¹Anuradha Nalli, ¹Bincy Jacob, ¹Deepthi Pantula, ¹Salil K Sukumaran, ¹Sapna Upendran, ¹Sashi Kanth Gollapudi, ¹Shweta Gupta, ¹Tanima De, ¹TS Keshava Prasad, ¹GS Sameer Kumar, ¹Malabika Sarker, ¹Sudhir Gopal Tattikota, ^2,3Gary D Bader, ³Chris Sander, ^1,4Akhilesh Pandey
¹Institute of Bioinformatics, International Tech Park, Bangalore-560066, India, ²University of Toronto, Toronto, Ontario M5S 3E1, Canada, ³Memorial-Sloan-Kettering Cancer Center, New York 10021, United States of America, ⁴The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States of America

Existing pathway resources in the public domain are mostly limited to specific lineage of interactions to define only a set of sub-pathways. NetPath is a freely available resource that contains comprehensive information on signal transduction pathways. The curation of pathway information and storage of data is achieved through a tool we developed called PathBuilder. PathBuilder facilitates easy retrieval and export into community standardized data structures such as BioPAX, PSI-MI and SBML. As an initial step, we have generated a set of immune signaling pathways namely B cell receptor, T cell receptor and 8 Interleukin pathways. Each pathway has information pertaining to protein-protein interactions, enzyme catalysis events and translocation of proteins within and across the sub-cellular compartments under ligand stimulation. The protein-protein interactions include binary interactions and interaction with functional complexes. For each catalysis or modification events that influences the status of molecules, the upstream enzyme and site of modification is curated whenever it was available.

This resource also contains genes which are reported to be differentially expressed under each pathway obtained by both microarray and non-microarray experiments from human source. A novel statistical method, which was recently reported by Draghici et al. 2007, was used to measure the impact factor for pathways in gene expression experiments. This approach can capture the magnitude of the expression changes of each gene, the position of the differentially expressed genes on the given pathways, the topology of the pathway that describes how these genes interact and the type of signaling interactions between them. The present set of immune signalling pathways include more than 1,100 reactions annotated from the literature and >2,400 instances of transcriptionally regulated genes in response to receptor stimulation from over 4,400 published articles. NetPath is available as a worldwide web resource from http://www.netpath.org/.