Opinion in 2013

Next-generation sequencing for variant identification is now becoming widespread, although pipelines have not yet been optimized. In this Perspective article, the authors discuss ways to minimize erroneous variant calls, in particular, by using replicates.

Bacterial whole-genome sequencing is showing promise in clinical applications. Here, the authors present their opinions on what the main bioinformatic challenges are in transferring bacterial whole-genome sequencing to medical diagnostics.

The authors discuss strategies and challenges of population-based studies of epigenetic variation. Such studies should contribute to our understanding of the contribution of epigenetic factors to human disease, but need to be performed and interpreted with consideration of their limitations.

The data from genome-wide association studies can be applied to genotype data to predict the phenotype of a complex trait. Here the authors discuss the potential pitfalls of such analyses and the inherent limitations of the method.

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.

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.

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.