Canadian scientists play major role in international effort to map the human epigenome

CEEHRC scientists contribute to the International Human Epigenome Consortium’s collection of 41 publications in Cell, Cell Press-associated and other high-impact journals

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.

“We are well on our way towards accomplishing our primary goal to create high quality reference maps of the epigenome for the scientific community,” said Martin Hirst (BC Cancer Agency and UBC), chair of the IHEC international scientific steering committee and CEEHRC Network leader. “Now that a baseline picture of the epigenome is taking shape, we can start to integrate information about the effects of the environment, aging and disease on the epigenome.”

Members of the Canadian Epigenetics, Environment and Health Research Consortium (CEEHRC) Network contributed seven papers to the IHEC collection.

Hirst and colleague Connie Eaves (BC Cancer Agency and UBC) published today in Cell Reports the first epigenetic profiles of normal cell types in human breast tissue. This information will help scientists understand how normal mammary glands develop and serve as a comparator for diseased tissues. Hirst’s group also published another study in Cell Reports today that reveals novel methodology for analyzing epigenomes, and applies it to understanding the biology of stem cells.

A team led by Marco Marra (BC Cancer Agency and UBC) used similar methods to identify epigenetic changes that are thought to contribute to the development of a rare childhood cancer called malignant rhabdoid tumour. This study was published in Cancer Cell earlier this year and is highlighted in the IHEC release as one of the 41 ground-breaking epigenomics papers.

A study co-led by researchers at McGill University and the Wellcome Trust Sanger Institute (UK) deciphers what causes the epigenomes of immune cells to vary among apparently healthy individuals. 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 (McGill University and Génome Québec Innovation Centre). “As more of the pieces are assembled, they provide potential new targets for therapeutic agents.”

One of the main initial challenges for 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 (McGill University and Génome Québec Innovation Centre) 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, is described in a new paper published in Cell Systems. Bourque's group also published a new computational method for analysing epigenomics data in Bioinformatics.

Gathering data on the human epigenome raises ethical questions, as well. Another paper in Cell by Yann Joly (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.”

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The full collection of IHEC papers is available at