Biology subjects

Smith, G.

Publications and source records attributed to Smith, G..

At least 73 records · Page 4Linked to original sources

bioRxiv2020

Coupled Control of Distal Axon Integrity and Somal Responses to Axonal Damage by the Palmitoyl Acyltransferase ZDHHC17

After optic nerve crush (ONC), the cell bodies and distal axons of most retinal ganglion cells (RGCs) degenerate. RGC somal and distal axon degeneration were previously thought to be controlled by two distinct pathways, involving activation of the kinase DLK and loss of the axon survival factor NMNAT2, respectively. However, we found that mutual palmitoylation by the palmitoyl acyltransferase ZDHHC17 couples the DLK and NMNAT2 signals, which together form a "trust, but verify system". In healthy optic nerves, ZDHHC17-dependent palmitoylation ensures NMNAT-dependent distal axon integrity, while following ONC, ZDHHC17-dependent palmitoylation is critical for DLK-dependent somal degeneration. We found that ZDHHC17 also controls survival-versus-degeneration decisions in sensory neurons and identified motifs in NMNAT2 and DLK that govern their ZDHHC17-dependent regulation. These findings suggest that the control of somal and distal axon integrity should be considered as a single, holistic process, involving two palmitoylation-dependent pathways acting in concert.

neuroscience↗

bioRxiv2020

Amino acids whose intracellular levels change most during aging alter chronological lifespan of fission yeast

Amino acid deprivation or supplementation can affect cellular and organismal lifespan, but we know little about the role of concentration changes in free, intracellular amino acids during aging. Here, we determine free amino-acid levels during chronological aging of non-dividing fission yeast cells. We compare wild-type with long-lived mutant cells that lack the Pka1 protein of the protein kinase A signalling pathway. In wild-type cells, total amino-acid levels decrease during aging, but much less so in pka1 mutants. Two amino acids strongly change as a function of age: glutamine decreases, especially in wild-type cells, while aspartate increases, especially in pka1 mutants. Supplementation of glutamine is sufficient to extend the chronological lifespan of wild-type but not of pka1{Delta} cells. Supplementation of aspartate, on the other hand, shortens the lifespan of pka1{Delta} but not of wild-type cells. Our results raise the possibility that certain amino acids are biomarkers of aging, and their concentrations during aging can promote or limit cellular lifespan.

physiology↗

bioRxiv2020

NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge

There is an urgent need for a safe and protective vaccine to control the global spread of SARS-CoV-2 and prevent COVID-19. Here, we report the immunogenicity and protective efficacy of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length SARS-CoV-2 spike (S) glycoprotein stabilized in the prefusion conformation. Cynomolgus macaques (Macaca fascicularis) immunized with NVX-CoV2373 and the saponin-based Matrix-M adjuvant induced anti-S antibody that was neutralizing and blocked binding to the human angiotensin-converting enzyme 2 (hACE2) receptor. Following intranasal and intratracheal challenge with SARS-CoV-2, immunized macaques were protected against upper and lower infection and pulmonary disease. These results support ongoing phase 1/2 clinical studies of the safety and immunogenicity of NVX-CoV2327 vaccine (NCT04368988). HighlightsO_LIFull-length SARS-CoV-2 prefusion spike with Matrix-M1 (NVX-CoV2373) vaccine. C_LIO_LIInduced hACE2 receptor blocking and neutralizing antibodies in macaques. C_LIO_LIVaccine protected against SARS-CoV-2 replication in the nose and lungs. C_LIO_LIAbsence of pulmonary pathology in NVX-CoV2373 vaccinated macaques. C_LI

immunology↗

bioRxiv2020

Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate

Vaccine efforts against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the current COVID-19 pandemic are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. Here, we performed cryo-EM and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax based on a full-length spike protein formulated in polysorbate 80 (PS 80) detergent. Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared to published spike ectodomain structures. Interestingly, we also observed novel interactions between the spike trimers allowing formation of higher order spike complexes. This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen.

immunology↗

bioRxiv2020

Decadal changes in fire frequencies shift tree communities and functional traits

Global change has resulted in chronic shifts in fire regimes, increasing fire frequency in some regions and decreasing it in others. Predicting the response of ecosystems to changing fire frequencies is challenging because of the multi-decadal timescales over which fire effects emerge and the variability in environmental conditions, fire types, and plant composition across biomes. Here, we address these challenges using surveys of tree communities across 29 sites that experienced multi-decadal alterations in fire frequencies spanning ecosystems and environmental conditions. Relative to unburned plots, more frequently burned plots had lower tree basal area and stem densities that compounded over multiple decades: average fire frequencies reduced basal area by only 4% after 16 years but 57% after 64 years, relative to unburned plots. Fire frequency had the largest effects on basal area in savanna ecosystems and in sites with strong wet seasons. Analyses of tree functional-trait data across North American sites revealed that frequently burned plots had tree communities dominated by species with low biomass nitrogen and phosphorus content and with more efficient nitrogen acquisition through ectomycorrhizal symbioses (rising from 85% to nearly 100%). Our data elucidate the impact of long-term fire regimes on tree community structure and composition, with the magnitude of change depending on climate, vegetation type, and fire history. The effects of widespread changes in fire regimes underway today will manifest in decades to come and have long-term consequences for carbon storage and nutrient cycling.

ecology↗

bioRxiv2020

SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice

The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).

microbiology↗

bioRxiv2020

Ozone-induced changes in murine lung extracellular vesicle number and small RNA content

Inhalation exposure to ozone (O3) causes adverse respiratory health effects that result from airway inflammation, a complex response mediated by changes to airway cellular transcriptional programs. These programs may be regulated in part by a subset of microRNAs transferred between cells (e.g. epithelial cells and macrophages) via extracellular vesicles (EV miRNA). To explore this, we exposed female C57BL/6J mice to filtered air (FA), 1, or 2 ppm O3 by inhalation and collected bronchoalveolar lavage fluid (BALF) 21 hours later for markers of airway inflammation, EVs, and EV miRNA. Both concentrations of O3 significantly increased markers of inflammation (neutrophils and total protein) and the number of EVs in the BALF. Using high-throughput small RNA sequencing, we identified several differentially expressed (DE) BALF EV miRNAs after 1 ppm (16 DE miRNAs) and 2 ppm (99 DE miRNAs) O3 versus FA exposure. O3 concentration response patterns in EV miRNA expression were apparent, particularly for the two most highly expressed (miR-2137 and miR-126-3p) and lowly expressed (miR-378-3p and miR-351-5p) miRNAs. Integrative analysis of EV miRNA expression and airway cellular mRNA expression identified EV miR-22-3p as a candidate regulator of transcriptomic responses to O3 in airway macrophages. In contrast, we did not identify candidate miRNA regulators of mRNA expression data from conducting airways (predominantly composed of epithelial cells). In summary, our data show that O3 exposure alters EV release and EV miRNA expression, suggesting that further investigation of EVs may provide insight into their effects on airway macrophage function and other mechanisms of O3-induced respiratory inflammation.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pharmacology and toxicology↗

bioRxiv2020

Plasmids shape the diverse accessory resistomes of Escherichia coli ST131

The human gut microbiome includes beneficial, commensal and pathogenic bacteria that possess antimicrobial resistance (AMR) genes that exchange these predominantly through conjugative plasmids. Escherichia coli is a significant component of the gastrointestinal microbiome and is typically non-pathogenic in this niche. In contrast, extra-intestinal pathogenic E. coli (ExPEC) including ST131 may occupy other environments like the urinary tract or bloodstream where they express genes enabling AMR and host cell adhesion like type 1 fimbriae. The extent to which commensal E. coli and uropathogenic ExPEC ST131 share AMR genes remains understudied at a genomic level, and here we examined this using a preterm infant resistome. Here, individual ST131 had small differences in AMR gene content relative to a larger shared resistome. Comparisons with a range of plasmids common in ST131 showed that AMR gene composition was driven by conjugation, recombination and mobile genetic elements. Plasmid pEK499 had extended regions in most ST131 Clade C isolates, and it had evidence of a co-evolutionary signal based on protein-level interactions with chromosomal gene products, as did pEK204 that had a type IV fimbrial pil operon. ST131 possessed extensive diversity of selective type 1, type IV, P and F17-like fimbriae genes that was highest in subclade C2. The structure and composition of AMR genes, plasmids and fimbriae vary widely in ST131 Clade C and this may mediate pathogenicity and infection outcomes. Data SummaryThe following files are available on the FigShare project "Plasmids_ST131_resistome_2020" : O_LI The set of 794 AMR genes derived from [74] are available (with their protein sequence translation) at FigShare at doi: dx.doi.org/10.6084/m9.figshare.11961402. C_LIO_LI The AMR gene profiles per sample determined by their BLAST sequence similarity results against CARD are available at FigShare at doi: dx.doi.org/10.6084/m9.figshare.11961612. This dataset includes the PlasmidFinder results. It also includes other AMR database comparisons (ARG-ANNOT, ResFinder, MegaRes, VFDB and VirulenceFinder). C_LIO_LI The BLAST sequence similarity results for the fim, pil, pap and ucl operons genes versus 4,071 E. coli ST131 assemblies from Decano & Downing (2019) are available at FigShare at doi: dx.doi.org/10.6084/m9.figshare.11961711. C_LIO_LI The genome sequences and annotation files for reference genomes NCTC13441, EC958 and SE15, along with the assembled contigs for 83972 and 3_2_53FAA are available at FigShare at doi: dx.doi.org/10.6084/m9.figshare.11961813. C_LIO_LI The 4,071 E. coli ST131 genome assemblies from Decano & Downing (2019) are available at FigShare at doi: 10.6084/m9.figshare.11962278 (the first 1,680 assemblies) and at doi: dx.doi.org/10.6084/m9.figshare.11962557 (the second 2,391 assemblies). C_LI

genomics↗

bioRxiv2020

Detecting genetic variation and base modifications together in the same single molecules of DNA and RNA at base pair resolution using a magnetic tweezer platform.

Accurate decoding of nucleic acid variation is important to understand the complexity and regulation of genome function. Here we introduce a single-molecule platform based on magnetic tweezer (MT) technology that can identify and map the positions of sequence variation and multiple base modifications together in the same single molecules of DNA or RNA at single base resolution. Using synthetic templates, we demonstrate that our method can distinguish the most common epigenetic marks on DNA and RNA with high sensitivity, specificity and precision. We also developed a highly specific CRISPR-Cas enrichment strategy to target genomic regions in native DNA without amplification. We then used this method to enrich native DNA from E. coli and characterized the differential levels of adenine and cytosine base modifications together in molecules of up to 5 kb in length. Finally, we enriched the 5 UTR of FMR1 from cells derived from a Fragile X carrier and precisely measured the repeat expansion length and methylation status of each molecule. These results demonstrate that our platform can detect a variety of genetic, epigenetic and base modification changes concomitantly within the same single molecules.

genomics↗

bioRxiv2020

Discovery of a 382-nt deletion during the early evolution of SARS-CoV-2

To date, the SARS-CoV-2 genome has been considered genetically more stable than SARS-CoV or MERS-CoV. Here we report a 382-nt deletion covering almost the entire open reading frame 8 (ORF8) of SARS-CoV-2 obtained from eight hospitalized patients in Singapore. The deletion also removes the ORF8 transcription-regulatory sequence (TRS), which in turn enhances the downstream transcription of the N gene. We also found that viruses with the deletion have been circulating for at least four weeks. During the SARS-CoV outbreak in 2003, a number of genetic variants were observed in the human population [1], and similar variation has since been observed across SARS-related CoVs in humans and bats. Overwhelmingly these viruses had mutations or deletions in ORF8, that have been associated with reduced replicative fitness of the virus [2]. This is also consistent with the observation that towards the end of the outbreak sequences obtained from human SARS cases possessed an ORF8 deletion that may be associated with host adaptation [1]. We therefore hypothesise that the major deletion revealed in this study may lead to an attenuated phenotype of SARS-CoV-2.

microbiology↗

bioRxiv2019

A precision virtual crossmatch decision support system for interpretation of ambiguous molecular HLA typing data

Virtual crossmatch (VXM) compares a transplant candidates unacceptable antigens to the HLA typing of the donor before an organ offer is accepted and, in selected cases, supplant a prospective physical crossmatch. However, deceased donor typing can be ambiguous, leading to uncertainty in compatibility prediction. We have developed a web application that utilizes ambiguous HLA molecular typing data to assist in VXM assessments. The application compares a candidates listed unacceptable antigens to computed probabilities of all possible two-field donor HLA alleles and UNOS antigens. The VIrtual CrossmaTch for mOleculaR HLA typing (VICTOR) tool can be accessed at http://www.transplanttoolbox.org/victor. We reanalyzed historical VXM cases where a transplant centers manual interpretation of molecular typing results influenced offer evaluation. We found that VICTORs automated interpretation of ambiguous donor molecular typing data would influence VXM decisions. Standardized interpretation of molecular typing data, if applied to the match run, could also change which offers are made. HLA typing ambiguity has been an underappreciated source of immunological risk in organ transplantation. The VICTOR tool can serve as a testbed for development of allocation policies with the aim of decreasing offers refused due to HLA incompatibility.

immunology↗

bioRxiv2019

SVCurator: A Crowdsourcing app to visualize evidence of structural variants for the human genome

A high quality benchmark for small variants encompassing 88 to 90% of the reference genome has been developed for seven Genome in a Bottle (GIAB) reference samples. However a reliable benchmark for large indels and structural variants (SVs) is yet to be defined. In this study, we manually curated 1235 SVs which can ultimately be used to evaluate SV callers or train machine learning models. We developed a crowdsourcing app - SVCurator - to help curators manually review large indels and SVs within the human genome, and report their genotype and size accuracy.\n\nSVCurator is a Python Flask-based web platform that displays images from short, long, and linked read sequencing data from the GIAB Ashkenazi Jewish Trio son [NIST RM 8391/HG002], We asked curators to assign labels describing SV type (deletion or insertion), size accuracy, and genotype for 1235 putative insertions and deletions sampled from different size bins between 20 and 892,149 bp. The crowdsourced results were highly concordant with 37 out of the 61 curators having at least 78% concordance with a set of expert curators, where there was 93% concordance amongst expert curators. This produced high confidence labels for 935 events. When compared to the heuristic-based draft benchmark SV callset from GIAB, the SVCurator crowdsourced labels were 94.5% concordant with the benchmark set. We found that curators can successfully evaluate putative SVs when given evidence from multiple sequencing technologies.

genomics↗

bioRxiv2019

Assessing metadata and curation quality: a case study from the development of a third-party curation service at Springer Nature

Since 2017, the publisher Springer Nature has provided an optional Research Data Support service to help researchers deposit and curate data that support their peer-reviewed publications. This service builds on a Research Data Helpdesk, which since 2016 has provided support to authors and editors who need advice on the options available for sharing their research data. In this paper we describe a short project which aimed to facilitate an objective assessment of metadata quality, undertaken during the development of a third-party curation service for researchers (Research Data Support). We provide details on the single-blind user-testing which was undertaken, and the results gathered during this experiment. We also briefly describe the curation services which have been developed and introduced following an initial period of testing and piloting. This paper will be presented at the International Digital Curation Conference 2019, and has been submitted to the International Journal of Digital curation.

scientific communication and education↗

bioRxiv2019

Using Twitter To Generate Signals For The Enhancement Of Syndromic Surveillance Systems: Semi-Supervised Classification For Relevance Filtering in Syndromic Surveillance

We investigate the use of Twitter data to deliver signals for syndromic surveillance in order to assess its ability to augment existing syndromic surveillance efforts and give a better understanding of symptomatic people who do not seek health care advice directly. We focus on a specific syndrome - asthma/difficulty breathing. We outline data collection using the Twitter streaming API as well as analysis and pre-processing of the collected data. Even with keyword-based data collection, many of the tweets collected are not be relevant because they represent chatter, or talk of awareness instead of suffering a particular condition. In light of this, we set out to identify relevant tweets to collect a strong and reliable signal. For this, we investigate text classification techniques, and in particular we focus on semi-supervised classification techniques since they enable us to use more of the Twitter data collected without needing to label it all. In this paper, propose a semi-supervised approach to symptomatic tweet classification and relevance filtering. We also propose the use of emojis and other special features capturing the tweets tone to improve the classification performance. Our results show that negative emojis and those that denote laughter provide the best classification performance in conjunction with a simple bag of words approach. We obtain good performance on classifying symptomatic tweets with both supervised and semi-supervised algorithms and found that the proposed semi-supervised algorithms preserve more of the relevant tweets and may be advantegeous in the context of a weak signal. Finally, we found some correlation (r = 0.414, p = 0.0004) between the Twitter signal generated with the semi-supervised system and data from consultations for related health conditions.

epidemiology↗

bioRxiv2018

Predictive Modelling of The Dynamic Patterns of Thinkingin Attention-Deficit/Hyperactivity Disorder: DiagnosticAccuracy of Spatiotemporal Fractal Measures

BackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterized by executive function (EF) dynamics disturbances. Notwithstanding, current advances in translational neuroscience, no ADHD objective, clinically useful, diagnostic marker is available to date.\n\nObjectivesUsing a customized definition of EF and a new clinical paradigm, we performed a prospective diagnostic accuracy trial to assess the diagnostic value of several fractal measures from the thinking processes or inferences in a cohort of ADHD children and typically developing controls.\n\nMethodWe included children from age five to twelve diagnosed with a reference standard based on case history, physical and neurological examination, Conners 3rd Edition, and DSM-V. The index test consisted of a computer-based inference task with a set of eight different instances of the \"Battleships\" game to be solved. A consecutive series of 18 cases and 18 controls (n = 36) recruited at the primary paediatrics service from the Nelson Marlborough Health in New Zealand underwent the reference standard and the index test. Several fractal measures were obtained from the inference task to produce supervised classification models.\n\nResultsNotably, the summarized logistic regressions predicted probabilities from the eight games played by each children yielded a 100% classification accuracy, sensitivity and specificity in both a training and an independent testing/validating cohort.\n\nConclusionsFrom a translational vantage point the expeditious method and the robust results make this technique a promising candidate to develop a screening, diagnostic and monitoring system for ADHD, and may serve to assess other EF disturbances.

clinical trials↗

bioRxiv2018

Whole genome sequencing for predicting Mycobacterium abscessus drug susceptibility

Mycobacterium abscessus is emerging as an important pathogen in chronic lung diseases with concern regarding patient to patient transmission. The recent introduction of routine whole genome sequencing (WGS) as a replacement for existing reference techniques in England provides an opportunity to characterise the genetic determinants of resistance. We conducted a systematic review to catalogue all known resistance determining mutations. This knowledge was used to construct a predictive algorithm based on mutations in the erm(41) and rrl genes which was tested on a collection of 203 sequentially acquired clinical isolates for which there was paired genotype/phenotype data. A search for novel resistance determining mutations was conducted using an heuristic algorithm.\n\nThe sensitivity of existing knowledge for predicting resistance in clarithromycin was 95% (95% CI 89 - 98%) and the specificity was 66% (95% CI 54 - 76%). Subspecies alone was a poor predictor of resistance to clarithromycin. Eight potential new resistance conferring SNPs were identified. WGS demonstrates probable resistance determining SNPs in regions the NTM-DR line probe cannot detect. These mutations are potentially clinically important as they all occurred in samples predicted to be inducibly resistant, and for which a macrolide would therefore currently be indicated. We were unable to explain all resistance, raising the possibility of the involvement of other as yet unidentified genes.

microbiology↗

bioRxiv2018

A quantitative evaluation of MIRU-VNTR typing against whole-genome sequencing for identifying Mycobacterium tuberculosis transmission: A prospective observational cohort study

SummaryO_ST_ABSBackgroundC_ST_ABSMycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) typing is widely used in high-income countries for Mycobacterium tuberculosis typing. Whole-genome sequencing (WGS) is known to deliver greater specificity, but no quantitative prospective comparison has yet been undertaken.\n\nMethodsWe studied isolates from the English Midlands, sampled consecutively between 1 January 2012 and 31 December 2015. In addition to routinely performed MIRU-VNTR typing, DNA was extracted from liquid cultures and sequenced using Illumina technology. Demographic and epidemiological data were extracted from the Enhanced Tuberculosis Surveillance system maintained by Public Health England. Closely related samples, defined using a threshold of five single nucleotide variants (SNVs), were compared to samples with identical MIRU-VNTR profiles, with shared epidemiological risk factors, and to those with both characteristics.\n\nFindings1,999 patients were identified for whom at least one M. tuberculosis isolate had been MIRU-VNTR typed and sequenced. Comparing epidemiological risk factors with close genetic relatedness, only coresidence had a positive predictive value of over 5%. Excluding co-resident individuals, 18.6% of patients with identical MIRU-VNTR profiles were within 5 SNVs. Where patients also shared social risk factors and ethnic group, this rose to 48%. Only 8% of MIRU-VNTR linked pairs in lineage 1 were within 5 SNV, compared to 31% in lineage 4.\n\nInterpretationIn the setting studied, MIRU-VNTR typing and epidemiological risk factors are poorly predictive of close genomic relatedness, assessed by SNV. MIRU-VNTR performance varies markedly by lineage.\n\nFundingPublic Health England, National Institute of Health Research Oxford Biomedical Research Centre.

microbiology↗

bioRxiv2018

Control of artefactual variation in reported inter-sample relatedness during clinical use of a Mycobacterium tuberculosis sequencing pipeline

Contact tracing requires reliable identification of closely related bacterial isolates. When we noticed the reporting of artefactual variation between M. tuberculosis isolates during routine next generation sequencing of Mycobacterium spp, we investigated its basis in 2,018 consecutive M. tuberculosis isolates. In the routine process used, clinical samples were decontaminated and inoculated into broth cultures; from positive broth cultures DNA was extracted, sequenced, reads mapped, and consensus sequences determined. We investigated the process of consensus sequence determination, which selects the most common nucleotide at each position. Having determined the high-quality read depth and depth of minor variants across 8,006 M. tuberculosis genomic regions, we quantified the relationship between the minor variant depth and the amount of non-Mycobacterial bacterial DNA, which originates from commensal microbes killed during sample decontamination. In the presence of non-Mycobacterial bacterial DNA, we found significant increases in minor variant frequencies of more than 1.5 fold in 242 regions covering 5.1% of the M. tuberculosis genome. Included within these were four high variation regions strongly influenced by the amount of non-Mycobacterial bacterial DNA. Excluding these four regions from pairwise distance comparisons reduced biologically implausible variation from 5.2% to 0% in an independent validation set derived from 226 individuals. Thus, we have demonstrated an approach identifying critical genomic regions contributing to clinically relevant artefactual variation in bacterial similarity searches. The approach described monitors the outputs of the complex multi-step laboratory and bioinformatics process, allows periodic process adjustments, and will have application to quality control of routine bacterial genomics.

microbiology↗