Next‐generation technologies and data analytical approaches for epigenomics

Abstract

Epigenetics refers to the collection of heritable features that modulate the genome-environment interaction without being encoded in the actual DNA sequence. While being mitotically and sometimes even meiotically transmitted, epigenetic traits often demonstrate extensive flexibility. This allows cells to acquire diverse gene expression patterns during differentiation, but also to adapt to a changing environment. However, epigenetic alterations are not always beneficial to the organism, as they are, for example, frequently identified in human diseases such as cancer. Accurate and cost-efficient genome-scale profiling of epigenetic features is thus of major importance to pinpoint these "epimutations," for example, to monitor the epigenetic impact of environmental exposure. Over the last decade, the field of epigenetics has been revolutionized by several innovative "epigenomics" technologies exactly addressing this need. In this review, we discuss and compare widely used next-generation methods to assess DNA methylation and hydroxymethylation, noncoding RNA expression, histone modifications, and nucleosome positioning. Although recent methods are typically based on "second-generation" sequencing, we also pay attention to still commonly used array- and PCR-based methods, and look forward to the additional advantages of single-molecule sequencing. As the current bottleneck in epigenomics research is the analysis rather than generation of data, the basic difficulties and problem-solving strategies regarding data preprocessing and statistical analysis are introduced for the different technologies. Finally, we also consider the complications associated with epigenomic studies of species with yet unsequenced genomes and possible solutions.

Clinical Challenges in Diagnosing the Genetic Etiology of Hearing Loss

“…Modifier genes for deafness exist that can rescue the hearing loss phenotype, but these prove even more difficult to identify, likely again due to genetic heterogeneity [see chapter by Yousaf et al, this vol., pp. [73][74][75][76][77][78][79][80][81][82][83].…”

“…In unclear cases, traditional Sanger sequencing may be performed for verification. Next-generation sequencing platforms do allow for identification of DNA methylation, noncoding RNAs, and histone modifications [73] . However, the application of such technology is limited by our nascent understanding of the role of epigenetics in heritable hearing loss.…”

Forest tree genomics: 10 achievements from the past 10 years and future prospects

“…In recent years, epigenomics has emerged in parallel to the development of next-generation sequencing (NGS) techniques, genomic resources, and associated bioinformatics and biostatistics packages, together with the use of specific methods to identify DNA methylation marks. Three main methods for detecting DNA methylation at the genome-wide level have been applied to trees (Mensaert et al 2014;Rodriguez et al 2012; ESM_4.doc, ESM_5.doc): (1) methylation-sensitive amplification polymorphism (MSAP), (2) methylated DNA immunoprecipitation (MeDIP), and (3) whole-genome bisulfite sequencing (WGBS).…”

Translating Next-Generation Sequencing from Clinical Trials to Clinical Practice for the Treatment of Advanced Cancers

“…Epigenetics have been connected to dysregulation of gene function and alteration of gene expression patterns [18]. Epigenetic traits are flexible, reversible and influenced by the environment; including chemical, nutritional and physical influences [19]. Epigenetics can be responsible for silencing gene expression, which can be inherited and result in development of certain diseases, such as cancer [18].…”

“…This integral disruption of a human genome through epigenetic abnormalities, allows for tumorgenesis [18]. NGS can identify epigenetic features on a genomic scale [19]. Targeted therapies that reverse gene silencing are currently at the forefront for future epigenetic therapy [18].…”