One of the great mysteries in biology is how the many different cell types that make up our bodies are derived from a single cell and from one DNA sequence, or genome. We have learned a lot from studying the human genome, but have only partially unveiled the processes underlying cell determination. The identity of each cell type is largely defined by an instructive layer of molecular annotations on top of the genome – the epigenome – which acts as a blueprint unique to each cell type and developmental stage. Unlike the genome the epigenome changes as cells develop and in response to changes in the environment. Defects in the factors that read, write and erase the epigenetic blueprint are involved in many diseases. The comprehensive analysis of the epigenomes of healthy and abnormal cells will facilitate new ways to diagnose and treat various diseases, and ultimately lead to improved health outcomes.
A collection of 41 coordinated papers now published by scientists from across the International Human Epigenome Consortium (IHEC) sheds light on these processes, taking global research in the field of epigenomics a major step forward. A set of 24 manuscripts has been released as a package in Cell and Cell Press-associated journals, and an additional 17 papers have been published in other high-impact journals.
These papers represent the most recent work of IHEC member projects from Canada, the European Union, Germany, Japan, Singapore, and the United States. The collection of publications showcases the achievements and scientific progress made by IHEC in core areas of current epigenetic investigations.
Epigenetic variations in immune cells
A study co-led by researchers at McGill, in Montreal, and the Wellcome Trust Sanger Institute in the UK, for example, deciphers what causes the epigenomes of immune cells to vary among apparently healthy individuals. The researchers examined major types of immune cells from nearly 200 blood donors in the U.K. The results, published in Cell, indicate that differences in genetic make-up also account for most of the epigenetic variation among individuals. The findings enabled the researchers to identify how genetic variations linked to common inflammatory diseases – such as Crohn’s disease, multiple sclerosis and rheumatoid arthritis -- may perturb the functioning of immune cells.
“Correlating epigenetic changes with genetic variations is like putting together a gigantic puzzle,” said co-senior author Tomi Pastinen, an associate professor in McGill’s Department of Human Genetics. “As more of the pieces are assembled, they provide potential new targets for therapeutic agents.”
Data hub developed at McGill
One of the main initial challenges for the IHEC, founded in 2010, was to find a way to collect and organize data generated by different countries over a number of years. A solution proposed by the team of Guillaume Bourque at McGill was selected and adopted as the IHEC Data Portal. This resource is now the main online tool that gathers all the epigenetic datasets generated by the consortium. Since its launch, the portal has been used more than 15,000 times by scientists from over 100 countries. The data portal, and its ongoing development, are described in a new paper published in Cell Systems by Dr. Bourque and colleagues from the McGill University and Génome Québec Innovation Centre.
Gathering data on the human epigenome raises ethical questions, as well. Another paper in Cell, by Yann Joly and colleagues from McGill’s Centre of Genomics and Policy, analyzes the advantages and limitations of different strategies to share epigenome research data with the scientific community while protecting the identity of participant donors to a reasonable extent. “This is important to prevent loss of privacy and potential research data misuses,” Joly says. “As people become more familiar with new tools for sharing and protecting their health data, novel approaches such as registered access and open consent could facilitate streamlined data access in coming years.”
A global effort
Taken together, the collection of new studies “constitutes a major achievement for IHEC,” said Dr. Eric Marcotte from the Canadian Institutes of Health Research (CIHR) and Chair of the IHEC Executive Committee. “The number of papers and variety of topics addressed by this creative team of scientists from around the globe not only reflects the dynamic nature of this consortium, but is also evidence of the great strength that comes from bringing together complementary expertise, with the potential for far greater impact than an equivalent number of individual projects.”
The International Human Epigenome Consortium (IHEC) is a global consortium with the primary goal of providing free access to high-resolution reference human epigenome maps for normal and disease cell types to the research community. IHEC members support related projects to improve epigenomic technologies, investigate epigenetic regulation in disease processes, and explore broader gene-environment interactions in human health. Current full members of IHEC include: AMED-CREST/IHEC Team Japan; DLR-PT for BMBF German Epigenome Programme DEEP; CIHR Canadian Epigenetics Environment, and Health Research Consortium (CEEHRC); European Union FP7 BLUEPRINT Project; Hong Kong Epigenomics Project; KNIH Korea Epigenome Project; the NIH/NHGRI ENCODE Project; the NIH Roadmap Epigenomics Program; and the Singapore Epigenome Project.
McGill Epigenomics Mapping Centre
tony.kwan [at] mcgill.ca
Media Relations, McGill University
christopher.chipello [at] mcgill.ca