Review Articles in 2010

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.

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.

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.

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.

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.

This article discusses how genomic techniques are expected to provide new insights into important problems in conservation and to allow questions to be addressed that have previously not been tractable. The authors also offer advice on choosing the most appropriate genomic approaches for studying different aspects of conservation.

Cancer is fundamentally a disease of the genome and so high-throughput sequencing technologies offer great potential for improving our understanding of the biology and treatment of cancer. Experimental strategies, computational approaches and cancer-specific considerations for detecting different types of genomic alterations are discussed.

What determines whether a tissue or organism can regenerate? What are the cellular sources of regeneration? How are regenerative signals initiated and targeted, and what controls proliferation and patterning during regeneration? Studies in a range of model systems are addressing these key questions.

This Review describes the different types of computational environments — such as cloud and heterogeneous computing — that are increasingly being used by life scientists to manage and analyse large multidimensional data sets.

This article reviews the increasing range of genome-scale methods that are being used to analyse eukaryotic DNA replication. Studies in different species and of replication timing or origin location have yielded varying degrees of success; technical hurdles remain, but important biological insights have been gained.