Advancing epigenetics towards systems biology
The network has brought together systems biology and epigenetic methodologies by both collaborations between computational and experimental groups as well as by developing computational expertise within experimental epigenetics groups. This changed research landscape will be a lasting legacy of the project. A large number of published and upcoming papers represent the significant incorporation of computational methods into mainstream epigenetics and epigenomics. EpiGeneSys members have contributed to software compendia in large community efforts such as the EC collaborative project BLUEPRINT, IHEC (International Human Epigenome Consortium) and projects such as the US NIH Epigenomics and 4D-Nucleomics Roadmaps. Software implementing systems biology approaches to epigenetic problems is being deployed throughout the large EpiGeneSys community, and is being applied daily to generate a large number of publications. Partly as a result of these integration efforts many participating Institutes and Universities in Europe are making group leader appointments of mathematicians, physicists, and modellers into biology based departments. The reverse is also beginning to happen in some places.
Impact on science policy
By structuring research in epigenetics to move into systems biology, EpiGeneSys has increased the competitiveness of the European Research Area (ERA) in many different aspects ranging from scientific knowledge and technology, to medical applications and human health, to education and training, and public education as well as supporting EU policy. A feasibility study undertaken by the network showed that greater engagement with policy makers and other scientific bodies could ensure the right support for scientific research, both in the field of epigenetics and more generally, including promoting the right environment for investment in research, ensuring better collaboration across disciplines and the EU, and ensuring the right policies are in place in terms of education, long-term support and funding. As an open and inclusive network EpiGeneSys has had the cohesive strength to catalyse interdisciplinarity and pave the way for future translational research. Systems biology approaches are expected to be useful at the clinical level and in generating new hypothesis to understand mechanism behind disease origin.
As an important consideration for science policy makers it should also be mentioned that EpiGeneSys through its interdisciplinary approach and its contribution to all levels of research, from elucidating basic molecular mechanisms to developing new technologies and methodologies as well as providing novel types of diagnostic and therapeutic approaches plays an important role in contributing to the economy through a process of research leading to deployment and subsequently driving economic growth.
Epigenetics has the potential to be a key element in a paradigm change of our understanding of health and disease and fundamentally influence public health policies. Epigenetic modifications are normally used during the development and maintenance of different cell types, but faulty epigenetic regulation can cause lasting damage, leading to cancer and other diseases ranging from metabolic disorders such as diabetes, to heart disease and mental health conditions. In the last 30 years, epigenetically induced changes in gene expression have been linked to many different cancers, among them bowel, breast, lung, prostate, liver, ovarian and pancreatic cancer. DNA methylation levels seem also to affect factors influencing cancer risk, such as obesity, smoking and ageing. Epigenetics also play a role in the autoimmune diseases such as rheumatoid arthritis with aberrant levels of DNA methylation and histone modifications having been connected to increased levels of inflammatory proteins in affected bone joints. Epigenetics has also been linked to a range of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, and epigenetic changes have been observed in mental retardation disorders with severe intellectual disabilities. The last few years have seen increasing interest in investigating the epigenetic dimension of neuropsychiatric diseases such as schizophrenia, bipolar disorder and depression. The interdisciplinary approach of EpiGeneSys has greatly contributed to the continuing development of technologies and analysis methodologies which are necessary to advance the understanding of disease, particularly for sequencing techniques such as ChIP-seq, footprinting techniques (DNase-seq, ATAC-seq) with inference of nucleosome distributions, bisulfite sequencing in the area of DNA methylation as well as chromosome conformation capture. Single cell methods have added the power to understand heterogeneity of the genome, transcriptome and epigenome which may underlie disease progression and ageing.
Novel therapies and interventions
Precision medicine involves the collaboration of many disciplines, from molecular biology and chemistry to physics and computational science; it requires a seamless transition from basic research to translation medicine and on to the clinic. Research conducted in the context of EpiGeneSys has added to our knowledge about how epigenetic patterns can serve as biomarkers for the diagnosis of disease, the early identification of patients at risk of a disease and to trace or predict the efficiency of particular treatments in patients. This helps the stratification of patients into groups according to their type of response to a treatment.
EpiGeneSys views basic research and applied research as being complementary to each other and therefore both important and essential, a dichotomy basic – applied research should be avoided and instead the continuum and non-linear nature of research be recognised. The increasing number of cancer therapies would not have been possible without publicly funded research supporting investigation of cellular mechanisms. Improved communication with policy makers is needed to draw attention to the contribution that basic research makes to applied science. Investigating the molecular basis of life has led and will again lead to many game-changing breakthroughs.