Despite the past century witnessing considerable advances in our understanding of genetics, the success of genome-wide association studies (GWAS) in detecting putative causal variants has been tinged with disappointment as the effects found have been modest. Epigenetics promises a novel biological foundation of a new way of looking at common diseases because it responds to the environment and governs gene expression – thus potentially mediating a path from environmental effects to gene expression to behavior. The primary objective of the “EpiTrain” Research Training Network is to promote integrative training-through-research in the field of epigenetics, especially of young researchers, both pre- and post-doctoral level, within the frame of high quality international collaborations. By integrating academic and private institutions with specializations in technological, analytical and computational aspects of epigenetic research, the training program will not only provide insights into research techniques and paradigms complementary to the individual projects, but will also strengthen professional skills and enhance the career prospects of the fellows.
EpiTrain ITN publishable project summary –
EpiTrain was an international multidisciplinary research training network aiming to provide integrative training in epigenetics for early career within the frame of high quality international collaborations. The network comprised six partner institutions across Europe, including four academic partners and two industrial partners. A total of 10 early stage researched (ESR) and 6 experienced researcher (ER) research positions were active in the network.
The overall objective of EpiTrain is to develop a broad scale understanding of epigenetic processes in common disease. The project aims to achieve this by providing the EpiTrain Fellows with knowledge of epigenetic processes in common disease development and train them in the relevant technical and analytical aspects. Research efforts focus on the four broad thematic areas and research aims:
(1) Epigenetic Systems Biology Approach: Integrating epigenetic and genetic whole genome information to understand the aetiology of common diseases.
(2) Epigenetic Epidemiology: Epigenetic epidemiology analysis of human complex traits, predominantly using disease discordant twins.
(3) Epigenetic Technologies: Development and application of novel biological assays to characterize the epigenome
(4) Computational Epigenomics: Development of novel analytical approaches to quantify and analyze epigenetic variation.
Work carried out within the project –
Main results arising from the project:
EpiTrain includes four scientific work packages that span the EpiTrain Fellows work.
(WP1) Epigenetic Systems Biology integrates epigenetic and genetic whole genome information to understand the aetiology of common diseases. The work of seven Fellows fell within the scope of WP1. Their main results have contributed to progress in research areas spanning development and application of novel computational tools to integrate epigenetic and genetic data to functionally annotate EWAS findings, application of meta-analysis approaches and integrative epigenomic studies in complex disease,
(WP2) Epigenetic Epidemiology explores epigenetic epidemiology analysis of complex traits, predominantly using disease discordant twins. The work of five Fellows fell within the scope of WP2. Their main results have contributed to progress in research areas spanning epigenetic heritability, environmental epigenomics, impact of artificial reproduction technologies on epigenetic profiles, identification of epigenetic biomarkers for common disease, exploring the role of histone modifications in complex diseases, and profiling epigenetic twin concordance and discordance over time in the context of complex traits.
(WP3) Epigenetic Technologies focuses on the development of novel epigenomic assays and applications in epidemiologic studies. The work of three Fellows fell within the scope of WP3. Their main results have contributed to progress in research areas spanning novel technology development of targeted methylation markers, development of genome-wide surveys to detect differential methylation changes across disease and control samples with functional annotation follow up, and optimization of ChIP-Seq technologies.
(WP4) Computational Epigenomics explores, develops, and applies novel analytical and bioinformatics approaches to quantify and analyze epigenetic variation. The work of five Fellows fell within the scope of WP4. Their main results have contributed to significant progress in research areas spanning application multi-omic integrative computational approaches in complex disease, systematic evaluation of allele-specific DNA methylation, analytical approaches to quantify DNA methylation signals across different technologies, and development of novel algorithms to predict differential methylation.
A key objective of EpiTrain was to provide EpiTrain Fellows with a good understanding of epigenetic processes in common disease development and progressing, and training in the relevant technical and analytical aspects of the research. The project raised a team of 16 talented ESR and ER fellow, who have been trained thoroughly in diverse aspects of epigenetics, computational biology, statistical analysis, molecular techniques, and translational approaches. The EpiTrain network has organized overall seven training workshops and the EpiTrain fellows have attended a large number of courses and workshops, on average 11 training events per EpiTrain Fellow. The Fellows also undertook secondments to research institutions, including both commercial and academic placements, to enable collaborative projects, give an opportunity to experience both academic and industry settings, and enhance the overall training program. By integrating academic and private institutions with specializations in technological, molecular, analytical and computational aspects of epigenetic research, EpiTrain aimed to strengthen the professional skills and enhance the career prospects of EpiTrain Fellows.
- 34 peer-reviewed papers have been published as of February 28th2017. In addition,a number of manuscript currently under review (2 papers) and in preparation (2 papers).
- Results were presented by ESRs and ERs at many national, international conferences, symposia, and workshops (>50 oral and poster presentations)
- Two research symposia were organized in 2014 and 2017, comprising of altogether over 100 participants, including members of the wider European scientific audience.
All deliverables and milestones have been achieved.
Final results and their potential impact and use:
The long-term benefits of EpiTrain include generating a network of young researchers in epigenetics, development of skills and individual Fellow career planning, exchange of knowledge, establishment of new contacts and collaborations across contributing institutions. Impacts on research include contributions to the understanding of the role of epigenetics in human complex disease, with a focus on epigenetic systems biology, epigenetic epidemiology, epigenetic technologies, and computational epigenomics. This knowledge may not only gain insight into mechanisms underlying disease, but has potential for development to future translational, technology and commercial opportunities. Impacts on Fellows include training in both academic and private sector institutions, with effects on each fellow’s research advances and career development. Impact and contribution to the private sector has been considered as a number of technologies and applications have been developed within the network, and there are opportunities for companies to exploit these in partnership with the research teams involved.
EpiTrain MARIE-CURIE ITN
This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 316758.