CTTV020_epigenomes_of_cell_lines_PILOT___RNA. CTTV020_epigenomes_of_cell_lines_PILOT___RNA

There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard & complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target & compound studies to primary human cells and tissues from both healthy volunteers & patients. Within GSK there have been a small number of focussed studies to understand the relationship between transformed cell lines used in cellular assays and primary cell types using transcriptomic data. However, there is an opportunity to establish a systematic approach for performing this type of analysis on a broader scale across a large number of cell types with multiple genomic data sets. A collated list of cellular assays has been pulled together within GSK across DPUs and Molecular Discovery Research from which the cellular reagents used in these assays can be categorised as follows: (1) Transformed cell lines used across multiple programs (2) Primary human cells (3) Co-culture & complex cellular reagents (e.g. PBMC) We will perform a systematic analysis of transcriptomic & epigenomic profiles in cell types of interest.当前学界正积极构建更具人类生物学与疾病研究相关性的细胞检测体系，具体可通过采用经过充分表征的转化细胞系、原代细胞及复杂细胞模型（如共培养模型、三维培养模型）来实现。尽管该领域在开展非标准化复杂细胞检测以用于靶点验证与化合物药理学研究方面已积累了宝贵经验，但目前仍缺乏一套系统方法，用以判断细胞检测模型的扩展是否能切实提升其人类生物学与疾病研究相关性。日益丰富的公开转录组与表观基因组（DNA元件百科全书ENCODE、表观基因组路线图Epigenome Roadmap）数据集，为明确靶点与化合物研究所用细胞类型，与健康志愿者及患者来源的原代人类细胞、组织之间的关联关系提供了理想的参考基准。在葛兰素史克（GSK）内部，已有少量针对性研究借助转录组数据，探究细胞检测中所用转化细胞系与原代细胞类型之间的关联关系。然而，当前仍存在拓展空间：我们可构建一套系统方法，依托多套基因组数据集，针对大量细胞类型开展更具广度的此类分析。葛兰素史克（GSK）已跨各药物研发单元（DPUs）与分子发现研究部（Molecular Discovery Research）整合了一份细胞检测汇总清单，据此可将这些检测所用的细胞试剂划分为以下三类：(1) 多项目通用的转化细胞系；(2) 原代人类细胞；(3) 共培养及复杂细胞试剂（如外周血单个核细胞PBMC）。我们将针对目标细胞类型的转录组与表观基因组谱图开展系统性分析。