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SigNET KnowledgeBank

The SigNET KnowledgeBank is a free on-line resource from Kinexus to foster research into cell signalling to advance biomedical research in academia and industry. It was designed to aid our clients in the interpretation of their results from our suite of proteomics services.

The first KnowledgeBase launched in SigNET was PhosphoNET. PhosphoNET holds data on more than 177,000 phosphorylation sites in about 14,000 human proteins that have been collected from original research performed by collaborators, the scientific literature, and other reputable websites. In addition, PhosphoNET features another 789,000 predicted human phosphosites using our proprietary algorithms. With the PhosphoNET Evolution module, it provides information about cognate proteins in up to 22 other species that may share these phosphosites. With the Kinase Predictor Module, it also lists the top 50 kinases that Kinexus has determined with its proprietary prediction algorithms are mostly likely to target each known and predicted phosphosite.
PhosphoNET also features direct links to several other useful websites, and will continue to expand to become a premier portal for phosphoproteomics information. New capabilities in development include the identification of binding proteins that target specific phosphosites.

The second KnowledgeBase launched in SigNET was TranscriptoNET. It features comprehensive information on the mRNA expression levels of about 21,000 genes in about 600 types of human organs, tissues and cells as measured with gene microarrays.

The original data used in TranscriptoNET was retrieved from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO), which serves as a repository of experimental gene microarray results submitted by diverse academic and industrial laboratories around the world. With the aid of our academic collaborators, Kinexus has normalized the data from over 900 different studies with over 6000 biological specimens to permit investigations of gene expression and potential interactions that can only be undertaken with such a large dataset of over 125,000,000 gene expression measurements.
This normalization process was based on the identification of 60 genes that were commonly and highly expressed in all of the biological samples. TranscriptoNET has been built with several useful queries, including identification of genes that are differentially regulated in diverse human cancers. We hope that users will find this a powerful resource for development of new testable hypotheses.

Our third KnowledgeBase called DrugKiNET was developed to foster the identification and characterization of inhibitors of protein kinases for academic and industrial research. It features comprehensive information on over 800 compounds that have been experimentally determined to inhibit human protein kinases. This includes the retrieval of the lowest reported compound IC50, Ki and Kd values from several sources, including the National Center for Biotechnology Information (NCBI) PubChem Compound database, the Kinase SARfari database from the European Molecular Biology Laboratory (EMBL) European Bioinformatics Institute, The International Centre for Kinase Profiling at the University of Dundee, Ambit Biosciences and hundreds of original research publications. In some cases, estimates for IC50 values were derived from limited measurements of kinase inhibition at only one to three different concentrations of the compounds. Using over 105,000 experimentally tested, non-redundant kinase-compound pairs for training, we have developed two kinase inhibitor prediction algorithms to further predict another 200,000 kinase-compound interactions.

Other new SigNET KnowledgeBases in development include KinaseNET, OncoNET and KinATLAS. With detailed information about the 536 known human protein kinases, KinaseNET will include data on protein kinase structures, regulation, specificities, substrates, distribution, evolutionary conservation and inhibitors. OncoNET will feature comprehensive information on the mutations and mRNA expression levels for about 3,000 genes in diverse types of human cancers. KinATLAS will generate maps of protein kinase-substrate, protein kinase-drug and protein-protein interactions. The underlying databases have already been built. These will be released as soon as our resources permit the creation of website interfaces.