Overall Research Goals
The German epigenome programme DEEP will establish a coordinated network for interdisciplinary epigenome research in Germany. Within the next five years DEEP will generate 70 human and mouse reference epigenomes in primary cell/tissue types in normal and diseased states. The DEEP programme will initially focus on adipocytes, hepatocytes, macrophages/monocytes, fibroblasts, epithelial cells and T-memory/effector cells in the context of defined metabolic and inflammatory diseases. Epigenomes will be exclusively generated using next generation sequencing technologies. DEEP combines strong experimental and bioinformatic expertise to compile, deposite and visualize reference epigenomes in a public repository as a contribution to IHEC.
A major goal of DEEP is to functionally interpret the reference epigenomic data and to gain new insights into epigenetic regulation and dysregulation of cellular programmes in complex diseases with high socioeconomic impact. Disease-oriented investigations using mouse models and human cell systems within DEEP will directly address mechanistic aspects. The overarching goal of these projects is to understand cellular function by epigenetic control, both on the level of individual cell types and in their crosstalk, in the context of complex systemic diseases such as adipositas, fatty liver disease, bowel disease and rheumatoid arthritis. DEEP will be integrated in a series of national and international research programmes to establish a first network for epigenomic biomedical research in Germany. Along this line DEEP will constitute an open network to associate and integrate 30 new epigenome projects in emerging fields following a successful midterm review.
Epigenomic data production
The epigenome of a cell refers to the collection of DNA methylation, histone modifications, chromatin accessibility and the set of coding and non-coding RNA molecules (Bernstein et al. Nature Biotechnology, 2010). The DEEP consortium will generate 70 epigenomes produced by a coordinated network of six production units (SP2-1 to SP2-3). These centers will comprise complementary expertise to produce epigenomes at highest possible standards from human and mouse cells and tissues. One epigenome comprises the collection of whole genome bisulfite sequencing (WGBS), chromatin immunoprecipitation (ChIP-seq), chromatin-accessibility (DNAseI-seq) and deep sequencing of long/short RNAs (RNA-seq). The parallel operating data production units will have a disease and cell type specific focus and will closely collaborate with the disease-oriented project partners. They will actively contribute to downstream bioinformatic analysis and data-interpretation.
Four bioinformatics subprojects (SP1-1 to SP1-4) will deal with the collection, mapping, visualization, integration and interpretation of epigenomic data generated by the sequencing units. The Data Collection Center (DCC) located in Heidelberg (SP1-2) and the Data Analysis Center in Saarbrücken (SP1-1) comprise the bioinformatics core of the consortium. The DCC will be responsible for the pseudonymisation of samples, the collection of primary quality controlled data from the sequencing units. WGBS-, DNAse-seq, ChIP-seq data and RNA-seq data will be mapped and transferred to the DCC. All DACs will contribute to the development of novel concepts and server based software tools for the analysis and visualization of epigenomic data in the areas of DNA-methylation-, chromatin structure & modification- and functional RNA mapping.
Disease-oriented functional studies
A key element of the DEEP program is the study of disease-oriented aspects using comparative epigenomics. Complementary to these epigenomic approaches seven expert research groups will perform comparative functional epigenomic studies to validate and understand the epigenetic contribution in metabolic (SP4-1 and SP4-2) and inflammatory diseases (SP5-1 to SP5-3). The disease-oriented projects focus on adipositas, liver steatosis, rheumatoid arthritis and inflammatory bowel disease. All disease-oriented projects have a dual task within DEEP:
- they will provide purified cells/tissues of defined normal and diseased states for epigenomic analysis (adipocytes, monocytes, macrophages, hepatocytes, T-cells, fibroblasts, epithelial cells) and
- they will establish and apply model systems to (functionally) test hypotheses generated by the interpretation of comparative maps.
The projects will closely cooperate with the data production and the data analysis units to obtain novel insights in the pathophysiology of systemic diseases and to define possible targets for new diagnostics and therapeutic interventions.