LINCS Information FramEwork (LIFE) to Integrate and Analyze Diverse Data Set

该申请寻求资金来开发LIFE——一种新型信息系统，可以无缝集成由NIH集成网络细胞特征（LINCS）图书馆和其他筛选项目产生的各种数据集。LINCS计划的目的是产生一个广泛的参考集的细胞反应签名，以各种小分子和遗传扰动。目标是创建一个可持续的和广泛可获得的知识资源，以促进我们对维持健康发育的分子生物成分高度协调的相互作用以及它们的扰动如何导致疾病的理解。LINCS产生的数据跨越各种分析格式和技术，包括生化和单细胞表型反应，以及全基因组转录谱。该计划的成功关键依赖于有效的信息学解决方案，将各种（当前和未来）数据类型整合到连贯的数据集中，并使不同背景和不同目标的科学家可以访问、解释和操作这些数据。我们建议开发一种新的以知识为基础的生活

This application seeks funds to develop LIFE - a novel information system to seamlessly integrate diverse data set produced by the NIH Library of Integrated Network-Based Cellular Signatures (LINCS) and other screening programs. The LINCS program aims to generate an extensive reference set of cellular response signatures to a variety of small molecule and genetic perturbations. The goal is to create a sustainable and widely accessible knowledge resource to advance our understanding of the highly orchestrated interplay of molecular biological components in maintaining healthy development and how their perturbation causes disease. Data produced at LINCS span a variety of assay formats and technologies, including biochemical and single cell phenotypic responses, and genome-wide transcriptional profiling. The success of this initiative critically relies on an effective informatics solution to integrate the various (current and future) data types into coherent data sets and to make them accessible, interpretable, and actionable for scientists of different backgrounds and with different objectives. We propose to develop LIFE - a novel knowledge-based information system that will solve this challenge. Tremendous progress has been made during the last decade developing Semantic Web technologies with the goals of formalizing knowledge, linking information across different domains, and integrating heterogeneous data from diverse sources. LIFE will leverage these technologies and extend them further. LIFE will incorporate biomedical domain-level ontologies, including our recently developed BioAssay Ontology, to associate related data types and to provide a knowledge context of the LINCS assays and their outcomes. LIFE will be scalable with respect to information volume and complexity. A key novel feature of LIFE will be the potential to derive novel implicit knowledge by various inference mechanisms; similar to how humans obtain insights by (mentally) connecting different pieces of information. The overarching goal of the LIFE system is to help scientists to use data and results produced in the LINCS and other NIH screening programs in their own research and to support their translation towards the development of novel therapeutics.