Development of Human Protein Reference Database as an Initial Platform for Approaching Systems Biology in Humans

McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Genome Research (Impact Factor: 13.85). 10/2003; 10(10):2363-71. DOI: 10.1101/gr.1680803

ABSTRACT Human Protein Reference Database (HPRD) is an object database that integrates a wealth of information relevant to the function of human proteins in health and disease. Data pertaining to thousands of protein-protein interactions, posttranslational modifications, enzyme/substrate relationships, disease associations, tissue expression, and subcellular localization were extracted from the literature for a nonredundant set of 2750 human proteins. Almost all the information was obtained manually by biologists who read and interpreted >300,000 published articles during the annotation process. This database, which has an intuitive query interface allowing easy access to all the features of proteins, was built by using open source technologies and will be freely available at to the academic community. This unified bioinformatics platform will be useful in cataloging and mining the large number of proteomic interactions and alterations that will be discovered in the postgenomic era.

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Available from: Saravana R K Murthy, Aug 10, 2015
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    • "), the Biomolecular Interaction Network Database (Bader et al., 2003), the Biological General Repository for Interaction Data Sets (Stark et al., 2006), the Database of Interacting Proteins (Salwinski et al., 2004), the Human Protein Reference Database (Peri et al., 2003), IntAct (Aranda et al., 2010), the Molecular Interaction database (Chatr-aryamontri et al., 2007), the mammalian PPI database of the Munich Information Center on Protein Sequences (Pagel et al., 2005), PDZBase (a PPI database for PDZ domains; Beuming et al., 2005), and Reactome (Vastrik et al., 2007). The databases were downloaded from their corresponding web sites in October, 2011. "
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    ABSTRACT: The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 Wiley Periodicals, Inc.
    Journal of Neuroscience Research 02/2015; 93(2). DOI:10.1002/jnr.23503 · 2.73 Impact Factor
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    • "C) Functional classification of the proteins altered in AHC patients. Proteins were classified using the information provided by the Human Protein Reference Database [24]. Table 3 – List of the protein spots modulated in AHC patient platelets (releasate and remaining pellet after platelet activation) and fibroblasts identified by DIGE and MALDI-TOF/TOF mass spectrometry (p < 0.05 by application of the FDR correction method). "
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    Journal of proteomics 05/2013; 86. DOI:10.1016/j.jprot.2013.05.005 · 3.93 Impact Factor
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    • "The integrated complex trait networks (iCTNet) Cytoscape plug-in (Wang et al., 2011a) retrieves data from several sources to form integrated networks that can contain genes (proteins), tissues, phenotypes (diseases and traits), and drugs. The accessed databases included the Human Protein Reference Database (HPRD) (Peri et al., 2003), the UCSC genome browser v.18 (Kent et al., 2002); the GWAS catalog (January 2011) (Hindorff et al., 2009), (restricted to strong associations, p < 10 "
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    Neuroscience 09/2012; 226C:10-20. DOI:10.1016/j.neuroscience.2012.09.007 · 3.33 Impact Factor
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