The German Federal Ministry of Education and Research (BMBF) represented by the Project Management Agency within the German Aerospace Center (PT-DLR) launched the German Epigenome Program “DEEP” on 1 September 2012. DEEP receives an overall funding of approx. 16 Mio EUR and will run for 5 years.
Overall project goal
DEEP creates an interdisciplinary research platform of 17 subprojects linking 21 epigenomic mapping and functional analysis groups across Germany. As the German contribution to IHEC, the ‘International Human Epigenome Consortium’, DEEP will produce und functionally interpret 70 reference epigenomes of selected human (and some murine) cells and tissues using high-throughput technologies and state of the art bioinformatics analysis.
Cell-Types
DEEP will focus on cell-types connected to the following complex diseases with high socio-economic impact: metabolic diseases such as i) steatosis (hepatocytes, kupffer-cells) and ii) adipositas (adipocytes (small/large, visceral/subcutaneous), monocytes, macrophages), as well as inflammatory diseasessuch as iii) morbus crohn (Mucosa, Macrophages, T-memory/effector cells) and iv) rheumatic arthritis (fibroblasts, Macrophages, T-memory/effector cells). The profiling and interpretation of epigenetic signatures or epigenetic (dys)regulation shall contribute to the understanding of the diseases being analyzed and in combination with functional studies lead to the identification of intra- and intercellular networks. These could be starting points for the development of novel diagnostic and therapeutic strategies and biomarkers.
To reach this goal, DEEP will generate for each cell-type genome-wide epigenome maps, including: i) DNA methylation (whole genome bisulfite sequencing), ii) chromatin accessibility (sequencing of DNAse hypersensitive sites), iii) 6 core histone modifications (ChIP-Seq), iv) transcriptome (RNA-seq) v) standard genotyping (SNP-array). On the bioinformatics level new strategies, concepts and tools for the visualization, integration and interpretation of epigenomic high-througput data shall be established.
Scientific Platforms
Deep is assembled on three interacting scientific platforms: production of epigenomic mapping-data, bioinformatics analysis and method-development and functional analysis with disease-orientation (see Figure 1, Table 1). The disease-oriented platform will contribute expertise to isolate highly purified cell types/tissues for epigenomic mapping and will analyse cell type-/ tissue-associated aspects of the complex diseases. The epigenomic sequencing units will generate primary epigenomic mapping-data that will be submitted to a central data collection unit and interpreted in close collaboration with central bioinformatics units responsible for high quality public data deposition and deep functional interpretation. A programme coordination and communcation platform will monitor the quality controlled data generation and foster interactions between bioinformatics and experimental analysis groups across platforms. DEEP will further coordinate its activities with IHEC and other epigenetic initiatives to establish unified standards for epigenomic data and for scientific exchange. Along this line DEEP will support IHEC in its dissemination activities through a DEEP associated coordination office.
verview of the DEEP-network structure of subprojects organized in four platforms: i) functional analysis with disease-orientation, ii) production of epigenomic mapping-data, iii) bioinformatics analysis and method development and iv) programme coordination and communication. The figure shows the placement of subprojects in the platforms and their interactions (arrows). DNAseI-seq: DNAseI sequencing, WGBS: whole genome bisulfite sequencing, ChIP-seq: ChIP sequencing, RNA-seq: RNA sequencing, DCC: Data Collection Center, DAC: Data Analysis Center.
Why Epigenomics?
The deciphering of the human genome sequence has helped our understanding of biological processes in health and diseases. However, the way in which the genomic information is organized within the cell, through epigenetic processes, is known to play a major role in regulating gene expression and in controlling specific cellular functions. Epigenetics and epigenomics research explores those processes. They go beyond DNA-stored information and are essential for packaging and interpreting the genome, are fundamental to normal development and cell differentiation, and are increasingly recognized as being involved in human disease.
Mis-steps in epigenomic programming have been directly implicated in common human diseases such as diabetes, inflammation, cancer as well as in ageing. Importantly, epigenomic changes are potentially reversible by drug treatments. This has significant implications for the prevention and treatment of these major human diseases with regenerative medicine as a very promising clinical approach. Hence, it will be important to have reference epigenome maps of all relevant human cell types to evaluate the importance and the consequences of these epigenetic changes as well as their impact on health.
Differences in epigenetic profiles are known to be induced by environmental and nutrition changes, so that maps for reference epigenomes will greatly broaden our understanding of how the environment and nutrition will modulate epigenetic alterations. This new, non DNA-based, knowledge will have a major impact for novel avenues in preventing and diagnosing major human diseases.
Get to know some of the people behind IHEC and listen to their personal vision and opinions.
The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery
Highlighted Publications
IHEC is committed to rapidly share research outcomes with epigenetic scientists around the globe.
In November 2016, IHEC scientists released a collection of 41 coordinated publications in Cell, Cell Press-associated and other high-impact journals.
Moreover, please take a look at the various publications originating from the individual research endeavors related to IHEC by following the link to the respective project websites.
IHEC Cell Papers
The collection of 41 coordinated papers published by scientists from across IHEC consists of a set of 24 manuscripts released as a package in Cell and Cell Press-associated journals, and an additional 17 papers published in other high-impact journals.
Key research findings presented in the collection can be collated into four broad categories with a first group of papers presenting a series of molecular and computational approaches to deconvolute distinct epigenomic signatures from tissues that contain a mix of different cell types.
A second group of publications highlights IHEC’s significant efforts and investments to develop new computational tools for the access, distribution and sharing of epigenomic data via various channels to the community. The IHEC Data Portal is one example of the tools developed to bolster the more than 7,000 datasets and make them accessible for widespread usage in biology and medicine.
In a third category, datasets produced by IHEC members were used to investigate molecular mechanisms underlying different cellular processes in normal and abnormal cell development. These analyses may in future help doctors to target the right treatments to the right patients.
A fourth group of papers in the collection uses epigenomic information to characterize how genetic variants affect the expression of genes, and how these genes in turn contribute to disease.
The full collection of IHEC papers is available at: http://www.cell.com/consortium/IHEC
Courtesy of Cell Press
Individual Publications from IHEC-associated Projects
Funding calls
- Request for Information (RFI): Challenges and Opportunities in Understanding Nuclear Organization in Space and Time (4D Nucleome)July 18, 2018In 2015, the NIH launched the “4D Nucleome” (4DN) Common Fund Program that aims to understand the principles underlying nuclear organization in space and time, the role nuclear organization plays in gene expression and cellular function, and how changes in nuclear organization affect normal development as well as various diseases (https://commonfund.nih.gov/4Dnucleome ). The initial… Read more
- NIH Common Fund: 4D Nucleome Program Announces First Funding Opportunities November 26, 2014The NIH has issued six Funding Opportunity Announcements for the 4D Nucleome program. Some of these are open to applicants outside of the US, or to applications with partners outside of the US. Please feel free to share this information with other researchers in this area if you think they may be interested. For more information and details on how to apply, click the links… Read more
- Multilateral France-Germany-Canada call for proposals on Epigenomics of Complex Diseases November 14, 2014The Agence Nationale de la Recherche (ANR), the Bundesministerium für Bildung und Forschung (BMBF) and the Canadian Institutes of Health Research (CIHR) together with the Fonds de Recherche du Québec – Santé (FRQS) are launching a multilateral joint transnational call for proposals to support epigenomics of common and complex diseases. The call aims to promote and create strategic synergy and… Read more
- European Commission has published the first work programme and calls December 18, 2013European Commission has published the first work programme and calls for the health, demographic change and wellbeing challenge societal challenge of Horizon 2020 for 2014/15 a few days ago. Horizon 2020 is the EU Research and Innovation programme with nearly €80 billion of funding available (€7 billion for Health) over 7 years (2014 to 2020). The societal challenge ‘Health, demographic change… Read more
- Bilateral French-German call for proposals on Epigenomics of Common and Age-related Diseases February 20, 2013The Agence Nationale de la Recherche (ANR) is joining the BMBF (Bundesministerium für Bildung und Forschung – German ministry for education and research) to launch a joint call which aims to promote synergy and added value through the establishment of high-quality, interdisciplinary binational collaborations among researchers in France and Germany, in the field of human epigenomics. Key… Read more
- NIH Common Fund announces new funding opportunity for the epigenomics program January 11, 2013The Funding Opportunity Announcement (FAO) seeks proposals to develop novel tools and technologies for tissue-, cell-, or locus-specific manipulation of the epigenome. Proposals may also develop tools and technologies to enable epigenetic manipulation with precise temporal control. Also investigators at foreign institutions are eligible to apply. Read more
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