Dubovenko Alexey, Nikolsky Yuri, Rakhmatulin Eugene, Nikolskaya Tatiana
Clarivate Analytics, 1500 Spring Garden Street, Fourth Floor, Philadelphia, PA, 19130, USA.
Prosapia Genetics, Solana Beach, CA, 92075, USA.
Methods Mol Biol. 2017;1613:101-124. doi: 10.1007/978-1-4939-7027-8_6.
Analysis of NGS and other sequencing data, gene variants, gene expression, proteomics, and other high-throughput (OMICs) data is challenging because of its biological complexity and high level of technical and biological noise. One way to deal with both problems is to perform analysis with a high fidelity annotated knowledgebase of protein interactions, pathways, and functional ontologies. This knowledgebase has to be structured in a computer-readable format and must include software tools for managing experimental data, analysis, and reporting. Here, we present MetaCore™ and Key Pathway Advisor (KPA), an integrated platform for functional data analysis. On the content side, MetaCore and KPA encompass a comprehensive database of molecular interactions of different types, pathways, network models, and ten functional ontologies covering human, mouse, and rat genes. The analytical toolkit includes tools for gene/protein list enrichment analysis, statistical "interactome" tool for the identification of over- and under-connected proteins in the dataset, and a biological network analysis module made up of network generation algorithms and filters. The suite also features Advanced Search, an application for combinatorial search of the database content, as well as a Java-based tool called Pathway Map Creator for drawing and editing custom pathway maps. Applications of MetaCore and KPA include molecular mode of action of disease research, identification of potential biomarkers and drug targets, pathway hypothesis generation, analysis of biological effects for novel small molecule compounds and clinical applications (analysis of large cohorts of patients, and translational and personalized medicine).
由于其生物学复杂性以及高水平的技术和生物学噪声，对NGS及其他测序数据、基因变异、基因表达、蛋白质组学和其他高通量（组学）数据进行分析具有挑战性。解决这两个问题的一种方法是使用包含蛋白质相互作用、信号通路和功能本体的高保真注释知识库进行分析。该知识库必须采用计算机可读格式构建，并且必须包括用于管理实验数据、分析和报告的软件工具。在此，我们介绍MetaCore™和关键信号通路顾问（KPA），这是一个用于功能数据分析的集成平台。在内容方面，MetaCore和KPA包含一个涵盖不同类型分子相互作用、信号通路、网络模型以及涵盖人类、小鼠和大鼠基因的十个功能本体的综合数据库。分析工具包包括用于基因/蛋白质列表富集分析的工具、用于识别数据集中连接过度和连接不足蛋白质的统计“相互作用组”工具，以及一个由网络生成算法和过滤器组成的生物网络分析模块。该套件还具有高级搜索功能，这是一个用于组合搜索数据库内容的应用程序，以及一个名为通路图创建器的基于Java的工具，用于绘制和编辑自定义通路图。MetaCore和KPA的应用包括疾病研究的分子作用模式、潜在生物标志物和药物靶点的识别、通路假设生成、新型小分子化合物的生物学效应分析以及临床应用（对大量患者队列的分析以及转化医学和个性化医学）。
