Microbial genomics

Clinical metagenomic next-generation sequencing (mNGS) is rapidly moving from bench to bedside. This Review discusses the clinical applications of mNGS, including infectious disease diagnostics, microbiome analyses, host response analyses and oncology applications. Moreover, the authors review the challenges that need to be overcome for mNGS to be successfully implemented in the clinical laboratory and propose solutions to maximize the benefits of clinical mNGS for patients.

Next-generation sequencing has improved the identification and characterization of antimicrobial resistance. Focusing on sequence-based discovery of antibiotic resistance genes, this Review discusses computational strategies and resources for resistance gene identification in genomic and metagenomic samples, including recent deep-learning approaches.

This article reviews recent advances in ancient pathogen genomics, from methodological improvements in retrieving whole genomes to evolutionary analyses of ancient pathogens that remain relevant to public health. Focusing on the evolutionary history of the plague pathogen Yersinia pestis, the authors present unique insights afforded by the study of ancient pathogen genomes.

Genomics has transformed the field of microbiology, but remaining challenges will need to be tackled for its benefits to be felt globally.

A genomics-informed response to infectious disease has great potential to improve individual patient treatment as well as public health. This Comment discusses the ethical, legal and social challenges that will need to be overcome if clinical pathogen genomics is to be implemented successfully.

In a study in Nature Microbiology, Setoh et al. use deep mutational scanning to speed up viral evolution and identify key determinants of host tropism in Zika virus.

A fuller understanding of bacterial genomic variation could provide insight into host pathophysiology. A new study in Nature demonstrates that structural variants are highly prevalent in human gut microbiomes and that some associate with host disease risk factors.

Two meta-analyses of fecal metagenomics studies report the presence of a microbial signature that is predictive of colorectal cancer.

This Genome Watch article discusses the application of machine learning algorithms to predict the source of food-borne infections.

This month’s Genome Watch explores the genetic variability of the anti-malaria vaccine protein and discusses its significance for an efficacious intervention.

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.

Comparing the microbiomes of great apes enables an evolutionary perspective on microbial communities. This approach is revealing not only new insights about humans and what differentiates us from our closest relatives but also the factors that influence microbiome composition and the ways in which microbiomes diverge.

The virulence of viruses is a major determinant of the health burden of viral infections in humans and other species. In this article, Geoghegan and Holmes discuss how largely disparate research fields — theoretical modelling of virulence evolution and experimental dissection of genetic virulence determinants in laboratory model systems — can be bridged by considering real genomic data of viral evolution in a phylogenetic context. They describe the underlying principles of virulence evolution and how they apply to real-world viral infections and outbreaks of global importance.

High-throughput sequencing technologies have enabled comparative analysis of large numbers of diverse bacterial genomes. Such studies are providing insights into the genomic changes that accompany changes in host specificity, with possible implications for controlling transmission of pathogenic bacteria.

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.

With the increasing availability of microbial whole genomes, researchers are beginning to carry out genome-wide association studies (GWAS) in bacteria, viruses and protozoa. In this Review, the authors discuss the specific challenges and considerations associated with the application of GWAS methods to microorganisms and consider the future of microbial GWAS in the light of lessons learned from human studies.

Fungi are enormously diverse, not the least in potential genetic markers that can be used for high-throughput sequencing studies of the mycobiome. In this Review, Nilsson and colleagues provide advice for leveraging next-generation technologies to explore mycobiome diversity in different habitats.

Although viral sequences are important in taxonomy, classification has typically also required biological properties, thus excluding viruses that were identified by metagenomics. The proposals in this Consensus Statement, which are supported by the International Committee on Taxonomy of Viruses (ICTV), enable viruses that are discovered by sequence alone to be incorporated into virus classification.

Complex microbial communities shape the dynamics of various environments. In this Review, Knight and colleagues discuss the best practices for performing a microbiome study, including experimental design, choice of molecular analysis technology, methods for data analysis and the integration of multiple omics data sets.