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July 7, 2019  |  

Moving forward: recent developments for the ferret biomedical research model.

Since the initial report in 1911, the domestic ferret has become an invaluable biomedical research model. While widely recognized for its utility in influenza virus research, ferrets are used for a variety of infectious and noninfectious disease models due to the anatomical, metabolic, and physiological features they share with humans and their susceptibility to many human pathogens. However, there are limitations to the model that must be overcome for maximal utility for the scientific community. Here, we describe important recent advances that will accelerate biomedical research with this animal model. Copyright © 2018 Albrecht et al.

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July 7, 2019  |  

Culture- and metagenomics-enabled analyses of the Methanosphaera genus reveals their monophyletic origin and differentiation according to genome size.

The genus Methanosphaera is a well-recognized but poorly characterized member of the mammalian gut microbiome, and distinctive from Methanobrevibacter smithii for its ability to induce a pro-inflammatory response in humans. Here we have used a combination of culture- and metagenomics-based approaches to expand the representation and information for the genus, which has supported the examination of their phylogeny and physiological capacity. Novel isolates of the genus Methanosphaera were recovered from bovine rumen digesta and human stool, with the bovine isolate remarkable for its large genome size relative to other Methanosphaera isolates from monogastric hosts. To substantiate this observation, we then recovered seven high-quality Methanosphaera-affiliated population genomes from ruminant and human gut metagenomic datasets. Our analyses confirm a monophyletic origin of Methanosphaera spp. and that the colonization of monogastric and ruminant hosts favors representatives of the genus with different genome sizes, reflecting differences in the genome content needed to persist in these different habitats.

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July 7, 2019  |  

Meeting report: mobile genetic elements and genome plasticity 2018

The Mobile Genetic Elements and Genome Plasticity conference was hosted by Keystone Symposia in Santa Fe, NM USA, February 11–15, 2018. The organizers were Marlene Belfort, Evan Eichler, Henry Levin and Lynn Maquat. The goal of this conference was to bring together scientists from around the world to discuss the function of transposable elements and their impact on host species. Central themes of the meeting included recent innovations in genome analysis and the role of mobile DNA in disease and evolution. The conference included 200 scientists who participated in poster presentations, short talks selected from abstracts, and invited talks. A total of 58 talks were organized into eight sessions and two workshops. The topics varied from mechanisms of mobilization, to the structure of genomes and their defense strategies to protect against transposable elements.

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July 7, 2019  |  

Immunoglobulin gene analysis as a tool for investigating human immune responses.

The human immunoglobulin repertoire is a hugely diverse set of sequences that are formed by processes of gene rearrangement, heavy and light chain gene assortment, class switching and somatic hypermutation. Early B cell development produces diverse IgM and IgD B cell receptors on the B cell surface, resulting in a repertoire that can bind many foreign antigens but which has had self-reactive B cells removed. Later antigen-dependent development processes adjust the antigen affinity of the receptor by somatic hypermutation. The effector mechanism of the antibody is also adjusted, by switching the class of the antibody from IgM to one of seven other classes depending on the required function. There are many instances in human biology where positive and negative selection forces can act to shape the immunoglobulin repertoire and therefore repertoire analysis can provide useful information on infection control, vaccination efficacy, autoimmune diseases, and cancer. It can also be used to identify antigen-specific sequences that may be of use in therapeutics. The juxtaposition of lymphocyte development and numerical evaluation of immune repertoires has resulted in the growth of a new sub-speciality in immunology where immunologists and computer scientists/physicists collaborate to assess immune repertoires and develop models of immune action.© 2018 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

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July 7, 2019  |  

Complete genome sequences of four Salmonella enterica subsp. enterica serovar Senftenberg and Montevideo isolates associated with a 2016 multistate outbreak in the United States.

A multistate outbreak of 11 Salmonella infections linked to pistachio nuts occurred in 2016. In this announcement, we report the complete genome sequences of four Salmonella enterica subsp. enterica serovar Senftenberg and S. enterica subsp. enterica serovar Montevideo isolates from pistachios collected during the 2016 outbreak investigation.

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July 7, 2019  |  

Interpreting whole-genome sequence analyses of foodborne bacteria for regulatory applications and outbreak investigations.

Whole-genome sequence (WGS) analysis has revolutionized the food safety industry by enabling high-resolution typing of foodborne bacteria. Higher resolving power allows investigators to identify origins of contamination during illness outbreaks and regulatory activities quickly and accurately. Government agencies and industry stakeholders worldwide are now analyzing WGS data routinely. Although researchers have published many studies that assess the efficacy of WGS data analysis for source attribution, guidance for interpreting WGS analyses is lacking. Here, we provide the framework for interpreting WGS analyses used by the Food and Drug Administration’s Center for Food Safety and Applied Nutrition (CFSAN). We based this framework on the experiences of CFSAN investigators, collaborations and interactions with government and industry partners, and evaluation of the published literature. A fundamental question for investigators is whether two or more bacteria arose from the same source of contamination. Analysts often count the numbers of nucleotide differences [single-nucleotide polymorphisms (SNPs)] between two or more genome sequences to measure genetic distances. However, using SNP thresholds alone to assess whether bacteria originated from the same source can be misleading. Bacteria that are isolated from food, environmental, or clinical samples are representatives of bacterial populations. These populations are subject to evolutionary forces that can change genome sequences. Therefore, interpreting WGS analyses of foodborne bacteria requires a more sophisticated approach. Here, we present a framework for interpreting WGS analyses that combines SNP counts with phylogenetic tree topologies and bootstrap support. We also clarify the roles of WGS, epidemiological, traceback, and other evidence in forming the conclusions of investigations. Finally, we present examples that illustrate the application of this framework to real-world situations.

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July 7, 2019  |  

Genomic sequencing of Bordetella pertussis for epidemiology and global surveillance of whooping cough.

Bordetella pertussis causes whooping cough, a highly contagious respiratory disease that is reemerging in many world regions. The spread of antigen-deficient strains may threaten acellular vaccine efficacy. Dynamics of strain transmission are poorly defined because of shortcomings in current strain genotyping methods. Our objective was to develop a whole-genome genotyping strategy with sufficient resolution for local epidemiologic questions and sufficient reproducibility to enable international comparisons of clinical isolates. We defined a core genome multilocus sequence typing scheme comprising 2,038 loci and demonstrated its congruence with whole-genome single-nucleotide polymorphism variation. Most cases of intrafamilial groups of isolates or of multiple isolates recovered from the same patient were distinguished from temporally and geographically cocirculating isolates. However, epidemiologically unrelated isolates were sometimes nearly undistinguishable. We set up a publicly accessible core genome multilocus sequence typing database to enable global comparisons of B. pertussis isolates, opening the way for internationally coordinated surveillance.

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July 7, 2019  |  

sppIDer: a species identification tool to investigate hybrid genomes with high-throughput sequencing.

The genomics era has expanded our knowledge about the diversity of the living world, yet harnessing high-throughput sequencing data to investigate alternative evolutionary trajectories, such as hybridization, is still challenging. Here we present sppIDer, a pipeline for the characterization of interspecies hybrids and pure species, that illuminates the complete composition of genomes. sppIDer maps short-read sequencing data to a combination genome built from reference genomes of several species of interest and assesses the genomic contribution and relative ploidy of each parental species, producing a series of colorful graphical outputs ready for publication. As a proof-of-concept, we use the genus Saccharomyces to detect and visualize both interspecies hybrids and pure strains, even with missing parental reference genomes. Through simulation, we show that sppIDer is robust to variable reference genome qualities and performs well with low-coverage data. We further demonstrate the power of this approach in plants, animals, and other fungi. sppIDer is robust to many different inputs and provides visually intuitive insight into genome composition that enables the rapid identification of species and their interspecies hybrids. sppIDer exists as a Docker image, which is a reusable, reproducible, transparent, and simple-to-run package that automates the pipeline and installation of the required dependencies (https://github.com/GLBRC/sppIDer; last accessed September 6, 2018).

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July 7, 2019  |  

Clustering of circular consensus sequences: accurate error correction and assembly of single molecule real-time reads from multiplexed amplicon libraries.

Targeted resequencing with high-throughput sequencing (HTS) platforms can be used to efficiently interrogate the genomes of large numbers of individuals. A critical issue for research and applications using HTS data, especially from long-read platforms, is error in base calling arising from technological limits and bioinformatic algorithms. We found that the community standard long amplicon analysis (LAA) module from Pacific Biosciences is prone to substantial bioinformatic errors that raise concerns about findings based on this pipeline, prompting the need for a new method.A single molecule real-time (SMRT) sequencing-error correction and assembly pipeline, C3S-LAA, was developed for libraries of pooled amplicons. By uniquely leveraging the structure of SMRT sequence data (comprised of multiple low quality subreads from which higher quality circular consensus sequences are formed) to cluster raw reads, C3S-LAA produced accurate consensus sequences and assemblies of overlapping amplicons from single sample and multiplexed libraries. In contrast, despite read depths in excess of 100X per amplicon, the standard long amplicon analysis module from Pacific Biosciences generated unexpected numbers of amplicon sequences with substantial inaccuracies in the consensus sequences. A bootstrap analysis showed that the C3S-LAA pipeline per se was effective at removing bioinformatic sources of error, but in rare cases a read depth of nearly 400X was not sufficient to overcome minor but systematic errors inherent to amplification or sequencing.C3S-LAA uses a divide and conquer processing algorithm for SMRT amplicon-sequence data that generates accurate consensus sequences and local sequence assemblies. Solving the confounding bioinformatic source of error in LAA allowed for the identification of limited instances of errors due to DNA amplification or sequencing of homopolymeric nucleotide tracts. For research and development in genomics, C3S-LAA allows meaningful conclusions and biological inferences to be made from accurately polished sequence output.

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July 7, 2019  |  

Implementation of pharmacogenomics in everyday clinical settings.

Currently, germline pharmacogenomics (PGx) is successfully implemented within certain specialties in clinical care. With the integration of PGx in pharmacotherapy multiple stakeholders are involved, which are identified in this chapter. Clinically relevant pharmacogenes with their related PGx test are discussed, along with diagnostic test criteria to guide clinicians and policy makers in PGx test selection. The chapter further reviews the similarities and the differences between the guidelines of the Dutch Pharmacogenetics Working Group and the Clinical Pharmacogenetics Implementation Consortium which both support healthcare professionals in understanding PGx test results and help guiding pharmacotherapy by providing evidence-based dosing recommendations. Finally, clinical studies which provide scientific evidence and information on cost-effectiveness supporting clinical implementation of PGx in clinical care are discussed along with the remaining barriers for adoption of PGx testing by healthcare professionals.© 2018 Elsevier Inc. All rights reserved.

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July 7, 2019  |  

A universal SNP and small-indel variant caller using deep neural networks.

Despite rapid advances in sequencing technologies, accurately calling genetic variants present in an individual genome from billions of short, errorful sequence reads remains challenging. Here we show that a deep convolutional neural network can call genetic variation in aligned next-generation sequencing read data by learning statistical relationships between images of read pileups around putative variant and true genotype calls. The approach, called DeepVariant, outperforms existing state-of-the-art tools. The learned model generalizes across genome builds and mammalian species, allowing nonhuman sequencing projects to benefit from the wealth of human ground-truth data. We further show that DeepVariant can learn to call variants in a variety of sequencing technologies and experimental designs, including deep whole genomes from 10X Genomics and Ion Ampliseq exomes, highlighting the benefits of using more automated and generalizable techniques for variant calling.

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July 7, 2019  |  

Genome size estimation of Chinese cultured artemisia annua L.

Almost all of antimalarial artemisinin is extracted from the traditional Chinese medicinal plant Artemisia annua L. However, under the condition of insufficient genomic in- formation and unresolved genetic backgrounds, regulatory mechanism of artemisinin biosynthetic pathway has not yet been clear. The genome size of genuine A. annua plants is an especially important and fundamental parameter, which helpful for further insight into genomic studies of ar- temisinin biosynthesis and improvement. In current study, all those genome sizes of A. annua samples collected with Barcoding identification were evaluated to be 1.38-1.49 Gb by Flow Cytometry (FCM) with Nipponbare as the bench- mark calibration standard and soybean and maize as two internal standards individually and simultaneously. The ge- nome estimation of seven A. annua strains came from five China provinces (Shandong, Hunan, Chongqing, Sichuan, and Hainan) with a low coefficient of variation (CV, = 2.96%) wasrelative accurate, 12.87% (220 Mb) less than previous reports about a foreign A. annuaspecies with a single con- trol. It facilitated the schedule of A. annua whole genome sequencing project, optimization of assembly methods and insight into its subsequent genetics and evolution.

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