The goal of this project is to develop a database and functional genomic analysis platform specifically designed for the study of the biological consequences of mutations and sequence heterogeneity in human genes and their controlling regions. The product will comprise i) a comprehensive database of known single nucleotide polymorphisms (SNPs), splice variants, translocations, copy number changes, and other alterations in genetic sequence that change the sequence, transcription or translation of human, rat or mouse proteins; ii) a comprehensive knowledgebase of literature-reported associations between human, rat and mouse sequence heterogeneities and the functional consequences of those differences to protein levels, protein stability and half life, enzymatic activity, substrate specificity, protein complex formation, protein-protein and protein-compound interactions, transcription factor activity or any other characteristic of biological consequence; iii) a suite of software tools, building on the GeneGo MetaDiscovery platform. This product, by combining knowledge on the functional consequences of sequence variations with a best- in-class systems biology software platform, will be unique in the marketplace. The product will allow the user to search for known sequence variations and their functional effects, identify metabolic and signaling networks within which the altered proteins are acting, and to categorize diseases and adverse drug effects associated with sequence variations. The user will be able to quickly identify potential strategies and targets for therapeutic interventions to combat increased vulnerability to disease or toxicity, find alternative therapeutic approaches to avoid sequence-related altered pharmacology or absorption, distribution, metabolism, elimination or toxicity parameters (ADMET), identify biomarkers of adverse effects associated with sequence variations. The product will smooth the progress "personalized medicine" by facilitating the application of personal genetic profiles to identify optimal therapeutic strategies for illness and disease. This will be an invaluable tool for disease research, pharmaceutical discovery, toxicology and clinical medicine. It will market and sold by GeneGo as part of the MetaDiscovery suite of products.
Public Health Relevance Statement: Project narrative The goal of this project is to develop a computational platform for functional analysis of the biological consequences of mutations and sequence heterogeneity in human genes and their controlling regions.
Project Terms: Absorption; Address; Adverse drug effect; Adverse effects; Affinity; Algorithms; Amino Acid Sequence; Analysis, Data; Binding; Binding (Molecular Function); Biologic Characteristic; Biological; Biological Characteristics; Cell Communication and Signaling; Cell Signaling; Characteristic, Biologic; Clinical Medicine; Common Rat Strains; Computer Programs; Computer Software Tools; Computer software; Data; Data Analyses; Data Banks; Data Bases; Data Set; Databank, Electronic; Databanks; Database, Electronic; Databases; Dataset; Development; Disease; Disorder; Drug Side Effects; Enzymes; Gene Expression; Gene Transcription; Gene variant; Genes; Genetic; Genetic Alteration; Genetic Change; Genetic Diversity; Genetic Transcription; Genetic Variation; Genetic defect; Genotype; Goals; Half-Life; Half-Lifes; Heterogeneity; Human; Human, General; Imagery; Intermediary Metabolism; Intracellular Communication and Signaling; Investigators; Knowledge; Link; Literature; METBL; Mammals, Mice; Mammals, Rats; Man (Taxonomy); Man, Modern; Maps; Marketing; Medical Sciences, Clinical; Medicine; Metabolic; Metabolic Processes; Metabolism; Methods; Mice; Molecular Biology, Protein Sequencing; Molecular Interaction; Mouse Protein; Murine; Mus; Mutation; Network Analysis; Ontology; Pathway Analysis; Pathway interactions; Peer Review; Peptide Sequence Determination; Pharmaceutical Agent; Pharmaceuticals; Pharmacogenomics; Pharmacologic Substance; Pharmacological Substance; Pharmacology; Phase; Physicians; Polymorphism, Single Base; Post-Translational Modifications; Post-Translational Protein Processing; Posttranslational Modifications; Process; Process of absorption; Protein Modification; Protein Modification, Post-Translational; Protein Processing, Post-Translational; Protein Processing, Posttranslational; Protein Sequencing; Protein Structure, Primary; Protein/Amino Acid Biochemistry, Post-Translational Modification; Proteins; RNA Expression; RNA Splicing; Rat; Rattus; Reporting; Research; Research Design; Research Personnel; Researchers; SNP; SNPs; Science of Medicine; Sequence Determinations, Amino Acid; Sequence Determinations, Protein; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; Single Nucleotide Polymorphism; Software; Software Tools; Splicing; Structure; Study Type; Substrate Specificity; System; System, LOINC Axis 4; Systems Biology; Therapeutic; Therapeutic Intervention; Tools, Software; Toxic effect; Toxicities; Toxicology; Transcription; Transcription, Genetic; Translations; Treatment Side Effects; Variant; Variation; Variation (Genetics); Visual; Visualization; Xenobiotics; absorption; allelic variant; biological signal transduction; biomarker; clinical data repository; clinical data warehouse; combat; computer program/software; data repository; disease/disorder; drug clearance; drug metabolism; experiment; experimental research; experimental study; functional genomics; functional group; gene product; genetic profiling; genetic variant; genome mutation; human data; interest; intervention therapy; measurement of metabolism; metabolomics; pathway; protein complex; protein expression; protein function; protein sequence; relational database; research study; side effect; study design; success; therapy adverse effect; tool; transcription factor; treatment adverse effect
