Objective

Open Targets is a public-private initiative between EMBL-EBI, Wellcome Trust Sanger Institute, GlaxoSmithKine (GSK) and Biogen, generating evidence on the validity of therapeutic targets based on genome-scale experiments and analysis. The Open Targets Cell Line Epigenome Project focuses more specifically on the challenge of selecting appropriate cellular models for target validation and drug screening that exhibit sufficient relevance to pathways and phenotypes associated with a particular disease or biology. The implementation of more complex, disease relevant models through use of 3D culture, tissue slices and primary cells is improving the predictive power of in vitro assays. However, due to limitations in cell and tissue supply, scalability, assay reproducibility and amenability to genetic manipulation, there often remains a need to utilise transformed cell lines. Currently cell lines are often chosen based on historical usage even if they are a poor substitute for that cell type or tissue. To address the gap in data driven cell line and model selection, this project aims to establish a systematic approach to determine biological relevance through generation and analysis of transcriptomic and epigenomic data (RNA/ChIP/ATAC-seq). All data will be shared publicly, enabling biologists to select the most appropriate, predictive cellular model for their research and to establish optimal assay critical paths for translating target biology & compound pharmacology to the clinic.