Reactome: An Open Knowledgebase of Human Pathways

描述(由申请者提供)：我们寻求更新反应组人类生物途径和过程知识库的核心运营资金。Reactome是一个经过精心策划的知识库，可以作为开放获取的资源在线提供，生物研究社区的所有成员都可以自由使用和重新分发。它被遗传学家、基因组学研究人员、临床研究人员和分子生物学家用来解释高通量实验研究的结果，被寻求开发从基因组学研究中挖掘知识的新算法的生物信息学家使用，被系统生物学家用来构建正常和异常通路的预测模型。我们的管理系统在很大程度上依赖社区内独立调查人员的专业知识，他们在一批专门的管理人员的指导下，编写对人类生物途径的机器可读的精确描述。每条路径在发布之前都经过了广泛的检查和同行审查，以确保其事实准确性和与数据模型的一致性。证据追踪系统确保所有断言都得到主要文献的支持，并确保从动物模型中的同源事件推断出的人类分子事件具有可审计的推理链。Reactome描述的精选途径目前覆盖了基因组翻译部分的大约四分之一。我们还提供了一个由保守的机器学习方法预测的“功能相互作用”(FIS)网络，它覆盖了额外四分之一的翻译基因组，总共覆盖了大约50%的已知基因组。在接下来的五年里，我们寻求(1)将受管理的蛋白质和其他功能实体的数量增加到至少10,500个；(2)用代表疾病状态的1200个基因的变异反应来补充正常途径；(3)将Reactome F1网络的规模增加到15,000个分子；以及(4)加强网站和其他资源，以满足不断增长和多样化的用户社区的需求。

DESCRIPTION (provided by applicant): We seek renewal of the core operating funding for the Reactome Knowledgebase of Human Biological Pathways and Processes. Reactome is a curated knowledgebase available online as an open access resource that can be freely used and redistributed by all members of the biological research community. It is used by geneticists, genomics researchers, clinical researchers and molecular biologists to interpret the results of high-throughput experimental studies, by bioinformaticians seeking to develop novel algorithms for mining knowledge from genomics studies, and by systems biologists building predictive models of normal and abnormal pathways. Our curational system draws heavily on the expertise of independent investigators within the community who author precise machine-readable descriptions of human biological pathways under the guidance of a staff of dedicated curators. Each pathway is extensively checked and peer-reviewed prior to publication to ensure its factual accuracy and compliance with the data model. A system of evidence tracking ensures that all assertions are backed up by the primary literature, and that human molecular events inferred from orthologous ones in animal models have an auditable inference chain. Curated pathways described by Reactome currently cover roughly one quarter of the translated portion of the genome. We also offer a network of "functional interactions" (FIs) predicted by a conservative machine-learning approach, that covers an additional quarter of the translated genome, for a combined coverage of roughly 50% of the known genome. Over the next five years, we seek to (1) increase the number of curated proteins and other functional entities to at least 10,500; (2) to supplement normal pathways with variant reactions for 1200 genes representing disease states; (3) increase the size of the Reactome Fl network to 15,000 molecules; and (4) enhance the web site and other resources to meet the needs of a growing and diverse user community.