Large scale gene expression analysis of cellular states

描述(由申请人提供)：在这个项目中，我们的目标是为LINCS计划创建数据生成和分析的第一部分。具体地说，我们将使用布罗德研究所开发的一种新的全基因组表达谱分析方法(基于Luminex珠子分析)来分类各种小分子和遗传扰动在广泛的人类细胞系中的细胞后果。我们将在20种细胞类型中进行这些扰动，这些细胞类型是根据它们的生物多样性和广泛的科学界的兴趣而选择的。对于遗传扰动，我们将描述用4,000种社区感兴趣的小分子化合物(包括从MLPCN网络中出现的化合物)处理每一种细胞系的细胞后果。对于基因扰动，我们将对3000个人类基因进行功能增强和功能丧失的研究。由此产生的表情数据将不受限制地向公众开放，重要的是，将伴随着一系列分析工具，使研究人员能够通过网络界面查询数据。该项目已经过配置，以便a)可以在未来进行更大规模的工作，b)可以适应未来技术平台的变化，c)可以适应与其他类型数据的集成。

DESCRIPTION (provided by applicant): In this project we aim to create a first installment of data generation and analysis for the LINCS program. Specifically, we will use a novel approach to genome-wide expression profiling developed at the Broad Institute (based on a Luminex bead assay) to catalog the cellular consequences of diverse small-molecule and genetic perturbations in a breadth of human cell lines. We will perform these perturbations in 20 cell types chosen for their biological diversity and interest to the broad scientific community. For the genetic perturbations, we will profile the cellular consequences of treatment of each of these cell lines with 4,000 small-molecule compounds of interest to the community (including compounds emerging from the MLPCN network). For the genetic perturbations, we will perform both gain- and loss-of-function studies for 3,000 human genes. The resulting expression data will be made publicly available without restriction, and importantly, will be accompanied by a series of analytical tools that will enable researchers to query the data via a web interface. The project has been configured so that it a) can scale to larger efforts in the future, b) can accommodate technology platform changes in the future, and c) can accommodate the integration with other types of data.