Department of Biomedical Engineering, OHSU, Portland, OR, USA.
Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA.
Commun Biol. 2022 Oct 7;5(1):1066. doi: 10.1038/s42003-022-03975-9.
The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
细胞的表型及其潜在的分子状态受细胞外信号的强烈影响,包括生长因子、激素和细胞外基质蛋白。虽然这些信号通常受到严格控制,但它们的失调会导致与多种疾病相关的表型和分子状态。为了详细了解分子和表型变化之间的联系,我们生成了一个综合数据集,该数据集记录了 MCF10A 乳腺上皮细胞在暴露于 EGF、HGF、OSM、IFNG、TGFB 和 BMP2 配体后转录组、蛋白质组、表观基因组和表型反应。这些配体诱导的分子和细胞表型的系统评估构成了 LINCS 微环境 (ME) 扰动数据集,该数据集经过整理并可供社区广泛分析和开发新的计算方法(synapse.org/LINCS_MCF10A)使用。在说明性分析中,我们展示了如何使用此数据集发现与特定细胞表型相关的功能相关的分子特征。除了这些分析之外,该数据集还将作为更广泛的科学界的资源,用于挖掘生物学见解,比较不同分子模态中传递的信号,并开发用于综合数据分析的新计算方法。