摘要:
随着转录组及蛋白质组等多组学数据的低成本测定技术的不断成熟,不同生理或病理状态下的细胞反应数据得以大量积累. 研究者可以利用这些数据来探究生物内在机理、推断疾病发生与发展机制、寻找药物靶标. 美国国立卫生研究院于2010年启动了基于网络的细胞反应印记整合图书馆(Library of Integrated Network-based Cellular Signatures, LINCS)大数据计划,该计划通过在一系列扰动下的基因表达水平及其他细胞反应水平的变化建立了一个基于整合网络的细胞反应数据库,阐明在不同的基因和环境压力下细胞是如何反应的,将基础研究与临床治疗联系起来,从而推动转化医学的快速发展. 本文综述了LINCS计划的起源、意义、实验技术、质量控制、数据内容和分析工具,总结了LINCS计划产生的大数据在基因调控关系、疾病发生模式和药物不良反应等方面的应用研究.
Abstract:
Maturing low-cost acquisition technology of multi-omics data, e.g. transcriptome and proteome data, continues to generate extensive amounts of cellular response data in numerous physiological and pathological condition. Researchers can use these data to explore the mechanism of biological processes, infer the generation and development of diseases, and discover the targets of drugs. In 2010, the National Institutes of Health (NIH) launched a project named Library of Integrated Network-based Cellular Signatures (LINCS). The project established an integrated network-based cellular response database by measuring the change of gene expression and other levels of cellular response after a series of perturbations, illustrated that how cell reacts under multiple genetic and environmental stresses, and connected basic medical research and clinical therapy to promote the rapid development of translational medicine. Here we review the origin, significance, experimental technology, quality control, data content and analysis tools of the LINCS project. We also summarize the applied research of the LINCS project in the aspects of gene regulation, disease generation, and adverse drug reactions.