What can epigenomics do for you?

Abstract

In 1990, with the initial launch of a 15-year project to map and sequence the human genome, a new era of science began. However, even after its successful and early completion in 2001 [1], no one could have foreseen how, only a few years later, genome sequencing would explode to become a widely applied multi-purpose tool whose applications include the mapping of epigenetic modifications and the complete assessment of both coding and non-coding RNA transcripts. The game changer behind this explosion was the transition from the classic electrophoretic Sanger sequencing method, which had limited scalability, to image-based massively parallel 'sequencing-by-synthesis' platforms. It had already become clear in the early days of the post-genome era, before these technological breakthroughs, that there were additional layers to the primary sequence waiting to be uncovered, and a small number of pilot epigenome projects, including the Human Epigenome Consortium (HEC), were launched [2,3]. While on the right track, these early projects suffered from lacking the sequencing capacity required to tackle the multidimensional space of the epigenome. This obstacle was overcome in 2006, with the introduction of next generation sequencing platforms, and the NIH was commendably fast to capitalize on these developments by implementing both its ENCODE and 'Roadmap Epigenomics' projects. ENCODE aimed to utilize the newly generated epigenome maps to assist in discovering and assigning functional elements in the genome, while the Roadmap Epigenomics Program aimed to create reference maps for the majority of normal, primary cell types [4,5]. The success of these projects has helped to popularize epigenomics and has proved somewhat contagious, with additional consortia, such as the recently funded BLUEPRINT (European) and DEEP (German), arriving on the scene; the International Human Epigenome Consortium (IHEC) now coordinates international efforts. The core technologies used in these projects, and in general across the field, have stabilized over the years and standards are now largely agreed upon. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) [6,7] remains the standard assay for determining transcription factor binding, as well as for mapping the genome-wide distribution of histone modifications. Continued efforts to increase sensitivity and resolution has resulted in some recent technical improvements to the basic ChIP-seq method, in the form of nano-ChIP-seq [8] and ChIP-exo [9], respectively. By contrast, dozens of assays exist for DNA methylation [10], although most genome-wide studies are focused on just a few of these [11-13]. As costs continue to decrease, methods are converging on whole genome bisulfite sequencing [14], which had previously been prohibitively expensive. As with exome sequencing, the subject of Genome Biology's 2011 special issue [15], the driving force behind the ongoing explosion in epigenome studies, and data, has been an increase in sequencing capacity at reduced cost.