An integrated systems pharmacology platform for pharmacogenomic research

用于药物基因组研究的综合系统药理学平台

• 批准号: 7672029
• 负责人: Richard John Brennan
• 金额: $ 14.84万
• 依托单位: GENEGO, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7672029
• 关键词: Address; Adverse drug effect; Adverse effects; Affinity; Algorithms; Amino Acid Sequence; Binding; Biologic Characteristic; Biological; Biological Markers; Clinical Medicine; Computer software; Data; Data Analyses; Data Set; Databases; Development; Disease; Enzymes; Gene Expression; Genes; Genetic; Genetic Transcription; Genetic Variation; Genotype; Goals; Half-Life; Heterogeneity; Human; Imagery; Knowledge; Link; Literature; Maps; Marketing; Medicine; Metabolic; Metabolism; Methods; Mouse Protein; Mus; Mutation; Ontology; Pathway Analysis; Pathway interactions; Peer Review; Peptide Sequence Determination; Pharmacogenomics; Pharmacologic Substance; Pharmacology; Phase; Physicians; Post-Translational Protein Processing; Process; Proteins; RNA Splicing; Rattus; Reporting; Research; Research Design; Research Personnel; Signal Pathway; Signal Transduction; Single Nucleotide Polymorphism; Software Tools; Structure; Substrate Specificity; System; Systems Biology; Therapeutic; Therapeutic Intervention; Toxic effect; Toxicology; Translations; Variant; Visual; Xenobiotics; absorption; combat; drug clearance; drug metabolism; functional genomics; functional group; genetic profiling; genetic variant; human data; interest; metabolomics; protein complex; protein expression; protein function; research study; success; tool; transcription factor

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：本项目的目标是开发一个数据库和功能基因组分析平台，专门用于研究人类基因及其控制区域中突变和序列异质性的生物学后果。该产品将包括i）已知的单核苷酸多态性（SNP）、剪接变体、易位、拷贝数变化和改变人、大鼠或小鼠蛋白质的序列、转录或翻译的遗传序列中的其他改变的综合数据库; ii）文献报道的人类，大鼠和小鼠的序列异质性以及这些差异对蛋白质水平、蛋白质稳定性和半衰期、酶活性、底物特异性、蛋白质复合物形成、蛋白质-蛋白质和蛋白质-化合物相互作用的功能后果，转录因子活性或生物学后果的任何其他特征; iii）一套软件工具，建立在GeneGo MetaDiscovery平台上。该产品通过将序列变异的功能后果的知识与一流的系统生物学软件平台相结合，将在市场上独一无二。该产品将允许用户搜索已知的序列变异及其功能效应，识别改变的蛋白质作用的代谢和信号网络，并对与序列变异相关的疾病和药物不良反应进行分类。用户将能够快速识别潜在的策略和治疗干预的目标，以对抗增加的疾病或毒性的脆弱性，找到替代治疗方法，以避免序列相关的药理学或吸收，分布，代谢，消除或毒性参数（ADMET）的改变，识别与序列变异相关的不良反应的生物标志物。该产品将通过促进个人基因图谱的应用来确定疾病的最佳治疗策略，从而顺利推进“个性化医疗”。这将是疾病研究、药物发现、毒理学和临床医学的宝贵工具。它将由GeneGo作为MetaDiscovery产品套件的一部分进行营销和销售。