Review Articles in 2020

The development of successful anticancer therapies relies on identifying drug targets that are genuine cancer-specific vulnerabilities. In this article, Lin and Sheltzer discuss how the different genetic and pharmacological methods for identifying and characterizing cancer dependencies each have important strengths and limitations. Responsible and orthogonal use of these methods holds promise for maximizing the ability of preclinical research to translate into clinical benefit.

In this Review, several experts discuss progress in the decade since the development of transposon-based approaches for bacterial genetic screens. They describe how advances in both experimental technologies and analytical strategies are resulting in insights into diverse biological processes.

The role of DNA methylation in genomic imprinting and X-chromosome inactivation (XCI) is well documented, but other imprinting mechanisms exist. Here, the authors review the role of oocyte-derived histone H3 lysine 27 trimethylation in establishing autosomal imprinting and imprinted XCI.

Long-read sequencing is becoming more accessible and more accurate. In this Review, Logsdon et al. discuss the currently available platforms, how the technologies are being applied to assemble and phase human genomes, and their impact on improving our understanding of human genetic variation.

The capacity to regenerate tissue varies across different species and tissue types. The poor regenerative capacity of organs such as the heart and nervous system contributes to the aetiology of a number of serious diseases, including heart failure and Alzheimer disease. In this Review, Goldman and Poss discuss how genetic programmes of regeneration are regulated and how the control mechanisms might be adapted to treat human disease.

Genetic recombination is a fundamental biological process generating genetic variation by shuffling combinations of alleles. In this Review, Peñalba and Wolf focus on how sequencing-based approaches are providing diverse insights into recombination rate variation across levels of biological organization and timescales, from individual gametes of single individuals to populations through evolutionary history.

Wilkinson and colleagues discuss haematopoietic stem cell (HSC) self-renewal in mice and humans. Experimental techniques for assaying HSC self-renewal are addressed, along with biological mechanisms regulating HSC self-renewal in vivo and ex vivo, and the therapeutic implications of this understanding.

Understanding evolutionary relationships between species requires the generation of accurate phylogenetic trees. In this Review, Kapli, Yang and Telford discuss the principles, steps and computational tools for phylogenetic tree building. They describe the impact of burgeoning genomic datasets as well as the diverse sources of errors and how they can be mitigated.

Colour traits have been useful for studying the genetics underlying adaptive evolution. This Review discusses how genomic technologies are providing a deeper understanding of these traits, revealing fresh insights into their genetic architecture, evolvability and origins of adaptive variation.

Genetic improvement of production traits in aquaculture has great potential to help meet the rising seafood demands driven by human population growth. The authors review how genomics is being applied to aquaculture species at all stages of the domestication process to optimize selective breeding.

Improvements in DNA extraction methods and sequencing technologies have led to the successful sequencing of numerous whole ancient genomes. In this Review, the authors provide an overview of how ancient DNA has informed our understanding of the domestication of various animal species, including dogs, pigs, cattle, goats and chickens.

Understanding developmental trajectories has recently been enabled by progress in modern lineage-tracing methods that combine genetic lineage analysis with omics-based characterization of cell states (particularly transcriptomes). In this Review, Wagner and Klein discuss the conceptual underpinnings, experimental strategies and analytical considerations of these approaches, as well as the biological insights gained.

Electronic health records (EHRs) linked to biobanks provide new opportunities for developing and applying polygenic risk scores in the clinic. The authors review the opportunities and challenges that arise when using EHR data for the systematic evaluation of patient disease susceptibilities.

With the increasing availability of ancient genomes from the same region or locality, the field of human history has started to address sociocultural aspects of human behaviour. The authors review recent case studies reconstructing the social consequences of past human migrations and advocate that this complex enterprise should be addressed by multidisciplinary teams.

Pollinators are critical for food security but bees, in particular, have experienced worrying population declines in recent years. This Review discusses how genomic technologies can be used to monitor and improve the health of managed and wild bee populations.

This Review outlines a broad, universal framework for systems biology applied to infectious disease research. From study design and omics data collection, analysis, visualization and interpretation to translational outcomes, the authors illustrate how systems biology can provide insights into host–pathogen relationships for the betterment of human health.

RNA interference (RNAi) effector proteins have highly conserved roles in chromosome function. This Review traces the evolutionary history of RNAi components and discusses their lesser-known roles in regulating chromosome segregation, gene dosage and DNA damage resolution, from unicellular eukaryotes to mammals.

Adeno-associated virus (AAV) vector-mediated gene delivery has had long-term therapeutic effects for several diseases, including haemophilia and Duchenne muscular dystrophy. Genetically modifying AAV vectors to increase their transduction efficiency, vector tropism and ability to avoid the host immune response may further increase the success of AAV gene therapy.

Although single reference genomes are valuable resources, they do not capture genetic diversity among individuals. Sherman and Salzberg discuss the concept of ‘pan-genomes’, which are reference genomes that encompass the genetic variation within a given species. Focusing particularly on large eukaryotic pan-genomes, they describe the latest progress, the varied methodological approaches and computational challenges, as well as applications in fields such as agriculture and human disease.

In this Review, Gasperini, Tome and Shendure discuss the evolving definitions of transcriptional enhancers, as well as diverse modern experimental tools to identify them. The authors describe how these diverse mindsets and methods provide differing but complementary insights into enhancers, each with notable strengths and caveats. They discuss how such views and approaches might be combined in a comprehensive catalogue of functional enhancers.