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Although cancer genome sequencing is becoming routine in cancer research, cancer transcriptome profiling through methods such as RNA sequencing (RNA-seq) provides information not only on mutations but also on their functional cellular consequences. This Review discusses how technical and analytical advances in cancer transcriptomics have provided various clinically valuable insights into gene expression signatures, driver gene prioritization, cancer microenvironments, immuno-oncology and prognostic biomarkers.
Genomic technologies are providing a clearer picture of how nuclear receptors (NRs) regulate complex transcriptional networks and contribute to the development and progression of cancer. This deeper understanding of NRs will hopefully lead to improved prognostic tools and new therapeutic targets.
Genetic architecture describes the characteristics of genetic variation that are responsible for phenotypic variability. This Review discusses the types of genetic architecture that have been observed, how they can be measured and how genetic architecture informs the scientific and clinical goals of human genetics.
In this Review, Kanieckiet al. discuss how the use of single-molecule optical microscopy and super-resolution optical microscopy methods has benefited our understanding of homologous recombination by generating detailed insights into the molecules and processes involved.
The rapid development of CRISPR-based gene manipulation has enabled various approaches for high-throughput functional genomics. This Review guides users through the practicalities of CRISPR-based functional genomics screens, including study design options, best-practice approaches, pitfalls to avoid and data analysis strategies.
The wealth of DNA methylation data continues to grow rapidly, including from epigenome-wide association studies (EWAS). However, extracting meaningful biological and clinical information requires diverse computational approaches for data analysis. This Review discusses the range of statistical tools available, including for cell-type deconvolution, identification of important methylation data features, causation and system-level integration with other types of omic data.
Next-generation sequencing has the potential to support public health surveillance systems to improve the early detection of emerging infectious diseases. This Review delineates the role of genomics in rapid outbreak response and the challenges that need to be tackled for genomics-informed pathogen surveillance to become a global reality.
Disease-resistant crops have the potential to reduce crop losses. This Review discusses how advances in genetic and genomic technologies are contributing to efforts by plant breeders to generate durable, broad-spectrum disease resistance in crop plants.
Sexual conflict is thought to increase population genetic diversity though balancing selection, which has important evolutionary implications. This Review discusses how population genomic approaches are contributing to a deeper understanding of sexual conflict and how it is resolved.
Identifying which genes in a genome are essential for survival has been a long-standing goal of geneticists. This Review discusses our evolving understanding of cellular gene essentiality across diverse organisms. It describes how essentiality is often non-absolute but is instead dependent on the environment or genetic background and how this knowledge can be exploited therapeutically.
The DNA methyltransferase (DNMT) family comprises a conserved set of DNA-modifying enzymes. Recent studies have increased our understanding of how DNMT activity is regulated and revealed that, in addition to establishing and maintaining DNA methylation patterns, DNMT enzymes function in transcriptional silencing, transcriptional activation and post-transcriptional regulation.
Despite being a single species, dogs represent nearly 400 breeds with substantial genetic, morphological and behavioural diversity. In this Review, Ostranderet al. discuss how genomics studies of dogs have enhanced our understanding of dog and human population history, the desired and unintended consequences of trait-based selective breeding, and potentially human-applicable insights into cancer, ageing, behaviour and neurological diseases.
Ancient genomes can inform our understanding of the history of human adaptation through the direct tracking of changes in genetic variant frequency across different geographical locations and time periods. The authors review recent ancient DNA analyses of human, archaic hominin, pathogen, and domesticated animal and plant genomes, as well as the insights gained regarding past human evolution and behaviour.
Advances in genome sequencing, editing and synthetic biology have enhanced the feasibility of large-scale genome engineering, termed genome writing. In this Opinion article, Chari and Church discuss the strengths and limitations of diverse strategies for genome writing, including extensively modifying existing genomes versus synthesizing genomesde novo, and they provide future visions for writing large genomes.
Recent microbiome genome-wide association studies have identified numerous associations between human genetic variants and the gut microbiome. Here, the authors review how genetic variation in the host can alter the composition of the gut microbiome towards a disease state, with a focus on disorders of immunity and metabolism.
Cell state transitions during embryonic development are associated with epigenetic changes that alter chromatin structure and gene expression. Interplay between epigenetic regulatory layers can be studied using genomic technologies and embryonic stem cell cultures that reflectin vivocell states.
For clinical cases of Mendelian disease that lack a genetic diagnosis, genome and exome sequencing are increasingly used for seeking the genetic cause. This Review discusses the strategies and computational tools for prioritizing the many genetic variants identified in each genome into those that are most likely to be causal for disease. The authors discuss how diverse types of biochemical, evolutionary, pedigree and clinical-phenotype information are used, and they highlight common pitfalls to be aware of for responsible variant prioritization.
The differentiation of an organism into a male or female phenotype is a critical developmental process, but the mechanisms that control this decision are remarkably evolutionarily labile. This Review discusses the wide diversity of vertebrate sex-determination mechanisms, their rapid evolution under different forms of genetic and environmental control and the over-arching principles that are shared despite this mechanistic diversity.
The last 25 years has seen a revolution in sequencing, with more than 100 vertebrate genome sequences now available. In this Review, Meadows and Lindblad-Toh discuss how the genomics of non-human organisms can provide insights into vertebrate biology and conservation, and how they can contribute to the understanding of human health and disease.
Recent studies have provided insights into the sources of endogenous replication stress, which can result in DNA damage, checkpoint activation and genome-wide replication fork slowing. The authors review established mechanisms involved in the replication stress response, and propose a new model that reconciles data gained from different cellular models.
