CTTV020_epigenomes_of_cell_lines_PILOT-sc-3526
CTTV020_epigenomes_of_cell_lines_PILOT
• To establish a systematic approach for the determination of human biological & disease relevance through the generation of epigenome data in cell types of interest.  • Integration of cell type epigenome data with existing & newly generated reference data from human tissue and cell types to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients.  • To provide a framework for the identification of optimal cell types for target identification/validation studies and drug discovery programs across multiple therapeutic areas.  • Development of bioinformatics pipelines and CTTV components for analysis and provision of data
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