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The Variome™ database is a series of 3-D protein modules derived from the DNA sequences of known disease targets. Each Variome™ module is composed of variant clinical genetic sequences isolated from tens-of-thousands of individual patient samples. Currently, there are two comprehensive database modules in Variome™ : 1) the HIV Protease module and 2) the HIV Reverse Transcriptase module. In Variome™ each genotype is transformed into a unique 3-D protein structure of X-ray crystallographic quality employing SBI's proprietary Augmented Homology Modeling™ process. There are over 30,000 variant structures in each module, with hundreds added weekly. The Variome™ aggregation of 3-D protein structural data provides key insights into the meaningful interactions between a drug and its polymorphic targets. By incorporating protein structural knowledge at the design stages of drug discovery, synthesis of drug candidates can be focused towards the highly conserved regions of the active binding site, permitting the assessment of drug efficacy prior to conducting clinical trials. Variome™ database modules are developed through a partnership with Quest Diagnostics, the world’s largest provider of diagnostic testing. Each module is based upon the genotypes of actual clinical sequences. All genetic codes are then converted into individual 3-D structures of X-ray crystallographic quality and cataloged to create the Variome™ database of structural variants.
Highlights Include: • Each Variome™ module offers nucleotide sequences and structural data, along with demographic, clinical, and temporal annotations. The information is accessed through SBI’s proprietary data mining tools, which enable analysis in a “user-friendly” format. • Empirically-derived table of drug resistance to the variants of HIV Protease and HIV Reverse Transcriptase, including a list of rules of resistance corresponding to various residue mutations. • Dynamic queries that return both sequence and structure information for subsequent analysis. Queries can be made by prevalence, incidence, specific mutations, drug resistance, clade, residue mutation ambiguity, specific sample identifier, date of sequencing, gender and/or region of sample, insertions and/or deletions, and deviation from reference sequence. • Accurately identifies the conserved and variant regions of both the genotype and structural phenotype. • Perfect for de novo drug design and in silico drug screening.
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