An integrated systems pharmacology platform for pharmacogenomic research

项目描述（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突变和序列异质性的生物学后果。该产品将包括i)已知单核苷酸多态性（snp）、剪接变异、易位、拷贝数变化和其他改变人类、大鼠或小鼠蛋白质序列、转录或翻译的基因序列改变的综合数据库；Ii)文献报道的人类、大鼠和小鼠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、转录因子活性或任何其他生物学后果特征的功能后果之间的关联的综合知识库；iii)一套软件工具，建立在GeneGo metaddiscovery平台上。该产品通过将序列变异的功能结果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影响，识别改变的蛋白质起作用的代谢和信号网络，并对与序列变异相关的疾病和不良药物效应进行分类。用户将能够快速确定治疗干预的潜在策略和目标，以对抗疾病或毒性增加的脆弱性，找到替代治疗方法，以避免与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，识别与序列变化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和疾病的最佳治疗策略，从而使“个性化医疗”的进展更加顺利。这将是疾病研究、药物发现、毒理学和临床医学的宝贵工具。它将作为metaddiscovery系列产品的一部分由GeneGo进行营销和销售。

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.