Reviews & Analysis

Our understanding of the molecular steps that occur during reprogramming somatic cells to induced pluripotent stem cells has recently been improved through analyses of cell populations and single cells. Here the authors consider the phases of reprogramming, models for describing the process and the roles of reprogramming factors.

Genome-wide data hold the key to answering long-standing questions about the mechanisms of speciation, including the role of gene flow. Here, the authors discuss recently developed methods to analyse genome-wide data and consider emerging results from their recent application.

The three-dimensional organization of genomes can now be explored at increased resolution using approaches based on 3C technology. This Review discusses how these chromatin interaction data sets can be interpreted using statistical approaches and computational modelling, and considers the levels of organization that are revealed.

The authors review statistical methods for meta-analysis of genome-wide association studies (GWASs) and extensions of these methods to complex data. They discuss how low-frequency variants can be incorporated into meta-analyses as next-generation sequencing data become more commonly used in GWASs.

Several promising genetic approaches are being investigated for the treatment of Duchenne muscular dystrophy, including traditional gene therapy, stop codon read-through, exon skipping and increased expression of a compensatory gene. The lessons learned should also be valuable for other disorders.

The recent explosion of genomics data has prompted the development of advanced algorithmic techniques to aid in the analysis, storage and retrieval of these data in the hunt for answers to biological questions. In this article, several examples of these algorithms are highlighted to aid in the use and selection of such algorithms.

This Review discusses the considerations for designing cancer genome-sequencing studies to fulfil different study aims, such as detecting recurrent mutations or assessing clonal evolution. For example, the cohort type and depth of sequencing can influence the downstream analysis.

Mosaicism refers to genetic heterogeneity within an organism that arises from postzygotic mutational events. This Review describes our latest understanding of the diverse types and widespread nature of mosaicism that underlies normal human variation and, in particular, a wide range of clinical diseases.

Recent genome-sequencing studies in human neurodevelopmental and psychiatric disorders have revealed mutations in chromatin-modifying enzymes, such as chromatin remodellers and histone-modifying enzymes. Such studies are improving our understanding of the roles of these modifiers in human neurodevelopment, and this article discusses the emerging roles for several of these enzymes in development and disease.

The concepts of orthology and paralogy are fundamental to comparative genomics and are also frequently used for the functional annotation of uncharacterized genes. However, assumptions regarding function have recently been challenged, and the implications of assigning genes as orthologues or paralogues are far from straightforward.

Although enhancers are crucial and widespread gene-regulatory elements, we are far from a complete understanding of how they function or their importance in areas such as disease and evolution. Five prominent researchers discuss some of the key outstanding questions in enhancer biology.

Evolution by natural selection at genomic loci sculpts the sequence features of not just each immediate locus but also nearby chromosomally linked sites. However, the way that this occurs substantially varies among different species, and this Review discusses potential reasons for these disparities.

Clinical sequencing tests that focus on genes linked to specific diseases or phenotypes are increasingly widely being used. This article discusses how disease-targeting tests retain several advantages despite moves towards the clinical application of whole-genome or exome sequencing.

RNA-binding proteins (RBPs) are crucial for guiding mRNAs through the many steps from transcription to translation and decay. This Review discusses recent insights into the repertoire of RBPs, how they package RNA molecules and how they can connect different processing steps.

Functional interactions between proteins and within proteins results in co-evolutionary signatures in amino acid sequences that serve as clues to various forms of interdependence. This Review discusses the principles and distinctions of the large range of computational tools to analyse protein co-evolution and the biological insight that they are providing.

The authors review new tools for studying the evolution of antibiotic resistance, including approaches to evolve resistance in the laboratory and analysis of clinical samples. Insights into pathways of evolution and the basis of resistance could inform future management of infections.

How much transgenerational epigenetic inheritance takes place, and what impact does this have on organisms? We asked five leading researchers — working on key model organisms and on human disease — for their views.

In this Opinion article, the authors discuss models that could explain the evolution of stress-induced mutagenesis in bacteria. They include a new model that argues that genetic drift could have a role in the evolution of low-fidelity DNA polymerases.

Advances in epigenomic and genetic studies have shown that DNA methylation undergoes local and global changes during mammalian development. This Review discusses the dynamics of this important epigenetic modification across various developmental stages.

Bacterial chromosomes were originally thought to be unstructured and largely unconstrained, but recent advances have supplemented historical research to reveal a highly structured and dynamic chromosome organization. This Review discusses our latest understanding of bacterial chromosome organization, including how the simultaneous nature of DNA replication and chromosome segregation in bacteria necessitates intricate interplay between these processes.