Reviews & Analysis

Recent developments in methods for RNA sequencing have led to an increased understanding of transcriptomes — both qualitative and quantitative. Ongoing developments include advances in direct RNA sequencing and approaches that allow RNA quantification from very small amounts of cellular materials.

This Progress article describes how the application of powerful technologies — based on bioinformatics, next-generation sequencing and biochemistry — has allowed us to map and characterize global adenosine-to-inosine RNA editing.

During development, boundaries between groups of cells that express different genes need to be established and maintained so that tissues can be patterned. This Review discusses the range of mechanisms — from feedback loops to physical forces — that have emerged as important for developmental boundaries.

Diseases are increasingly being found to reflect the perturbations of complex molecular networks. The principles of network medicine are being used to identify new disease genes, determine the functional significance of disease-associated mutations, and identify new drug targets and biomarkers.

Five experts discuss the challenges of making pharmacogenomics a reality.

The amount of genome-scale data on covalent histone modification patterns is rapidly increasing. This Review brings together current knowledge on how modification 'signatures' relate to the structure and function of chromatin, from regulatory elements and gene structure to organization in the nucleus.

To achieve their diverse regulatory functions, specific small RNA strands need to pair with the correct Argonaute protein partners. This Review discusses the recent substantial progress in understanding how small RNA sorting occurs in animals and plants.

Biases in synonymous codon usage are pervasive across taxa, genomes and genes, and understanding their causes has implications for molecular evolution and biotechnology. This article assesses the competing models for codon bias, in light of genome-scale and high-throughput data.

This article assesses the alternative methods for identifying natural alleles that control quantitative traits inArabidopsis thaliana, with a particular emphasis on the need to adapt study designs to account for the context of ecology and adaptation in nature.

Phenotypes are the key to a better understanding of the genotype–phenotype map and of the basis of disease and evolutionary fitness. The authors argue here that phenomics — comprehensive phenotyping on an organism-wide scale — will bring benefits at least as great as the Human Genome Project.

Analytical methods that use knowledge of biological pathways are being developed to extract more information from genome-wide association studies and to guide follow-up studies. This Review discusses the use of pathway-based analysis, the available tools, statistical considerations and directions for future improvements.

Genome-wide studies of protein–DNA interactions are helping to provide a more complete picture of the regulation of transcriptional programmes during plant development. Models of regulation have evolved from hierarchies of transcription factors to complex networks that involve these factors and chromatin-modifying proteins.

Prediction of genetic values using whole-genome markers has been successfully applied in commercial breeding. This article outlines the use of this method for predicting health-related outcomes in humans.

Genomic rearrangements cause human genomic disorders and are implicated in many cancers. Many rearrangements do not occur at random and this Review brings together recent findings on different influences — from nuclear organization to DNA sequence — that affect where and when rearrangements happen.

Many models have been proposed to explain how and why trinucleotide repeats in the human genome can expand and cause disease. This Review re-evaluates such models in the light of our knowledge of where and when instability occurs during human development.

The multisubunit Mediator complex is a transcriptional co-activator that interacts directly with RNA polymerase II. The Mediator can also interact with and coordinate the action of numerous other co-activators and co-repressors, leading to distinct transcriptional outputs in response to different cellular signals.

There is increasing interest in investigating the influence of rare variants on common diseases, aided by high-throughput sequencing. However, the statistical approaches that are essential for analysing associations between rare variants and traits of interest are urgently in need of evaluation and refinement.

Chronic stress is increasingly implicated as a contributing factor in common diseases, including cancer, cardiovascular disease and diabetes. This Opinion article brings together evidence supporting the idea that stress can induce epigenetic changes that alter cell behaviour and thereby lead to disease.

Identity by descent (IBD) — the probability that two alleles descended from a common ancestor — is used in fundamental applications such as gene mapping and estimating heritability. The authors offer a solution to the confusion between IBD and identity by state (IBS) that is caused by the common practice of using dense SNPs to estimate IBD.

Understanding the intrinsic sequence specificity of proteins — particularly of transcription factors — that interact with DNA is an important component of studies of gene regulation. Several recently developed methods have greatly increased the throughput of protein–DNA interaction studies, and the sophistication of computational modelling is improving.