Future potential of the Human Epigenome Project

Abstract

Deciphering the information encoded in the human genome is key for the further understanding of human biology, physiology and evolution. With the draft sequence of the human genome completed, elucidation of the epigenetic information layer of the human genome becomes accessible. Epigenetic mechanisms are mediated by either chemical modifications of the DNA itself or by modifications of proteins that are closely associated with DNA. Defects of the epigenetic regulation involved in processes such as imprinting, X chromosome inactivation, transcriptional control of genes, as well as mutations affecting DNA methylation enzymes, contribute fundamentally to the etiology of many human diseases. Headed by the Human Epigenome Consortium, the Human Epigenome Project is a joint effort by an international collaboration that aims to identify, catalog and interpret genome-wide DNA methylation patterns of all human genes in all major tissues. Methylation variable positions are thought to reflect gene activity, tissue type and disease state, and are useful epigenetic markers revealing the dynamic state of the genome. Like single nucleotide polymorphisms, methylation variable positions will greatly advance our ability to elucidate and diagnose the molecular basis of human diseases.

Molecular studies of major depressive disorder: the epigenetic perspective

“…This is one of the targets of the Human Epigenome Project (www.epigenome.org), which aims to map all methylation variable positions in the genome. 113 Producing a reference map of the entire human epigenome is going to be a gargantuan task, especially given the huge epigenetic differences that are likely to occur both between tissue/cell types, and within a specific tissue/cell type over the course of development. To date, this private/public consortium has released DNA methylation profiles of the major histocompatibility complex 114 and chromosomes 6, 20 and 22.…”

Epigenetics: from the past to the present

“…The goal of deciphering the 'human epigenetic code' will only be achieved once the pattern of imprinted marks on histones in chromatin is determined. At present, there is already DNA methylation profiling of human chromosomes 6, 20 and 22, there are the reference epigenomes from 127 tissue and cell types and the integrative analysis of 111 of these epigenomes (Eckhardt et al 2004;Eckhardt et al 2006;Jones et al 2008;Bernstein et al 2010). Nowadays, the scientific community is making efforts for the development and improvement of tools and technologies that facilitate the storage, management and analysis of data obtained from study models.…”

The role of longitudinal cohort studies in epigenetic epidemiology: challenges and opportunities

“…Pre-processing of data is often necessary to generate comparable data from samples between and within individuals over time. International initiatives to address and reach consensus on such issues are in progress [65]. Equally important is that many of these methods seek to optimize the signal-to-noise ratio.…”

“…International efforts to create reference epigenomes from homogeneous cell samples will be highly beneficial [65]. However, variation due to cellular and tissue heterogeneity is just one example of the wide breadth of issues regarding noise that require detailed and systematic study.…”