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  1. Article ; Online: High-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection

    Erica Normandin / Melissa Rudy / Nikolaos Barkas / Stephen F. Schaffner / Zoe Levine / Robert F. Padera / Mehrtash Babadi / Shibani S. Mukerji / Daniel J. Park / Bronwyn L. MacInnis / Katherine J. Siddle / Pardis C. Sabeti / Isaac H. Solomon

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 12

    Abstract: Here, by high-resolution SARS-CoV-2 sequencing, genomic and transcriptomic analyses from tissue samples, Normandin et al. investigate viral dynamics in fatal cases of COVID-19, revealing persistent infection in distinct anatomical sites, including the ... ...

    Abstract Here, by high-resolution SARS-CoV-2 sequencing, genomic and transcriptomic analyses from tissue samples, Normandin et al. investigate viral dynamics in fatal cases of COVID-19, revealing persistent infection in distinct anatomical sites, including the heart and testis.
    Keywords Science ; Q
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Detection of low-density Plasmodium falciparum infections using amplicon deep sequencing

    Angela M. Early / Rachel F. Daniels / Timothy M. Farrell / Jonna Grimsby / Sarah K. Volkman / Dyann F. Wirth / Bronwyn L. MacInnis / Daniel E. Neafsey

    Malaria Journal, Vol 18, Iss 1, Pp 1-

    2019  Volume 13

    Abstract: Abstract Background Deep sequencing of targeted genomic regions is becoming a common tool for understanding the dynamics and complexity of Plasmodium infections, but its lower limit of detection is currently unknown. Here, a new amplicon analysis tool, ... ...

    Abstract Abstract Background Deep sequencing of targeted genomic regions is becoming a common tool for understanding the dynamics and complexity of Plasmodium infections, but its lower limit of detection is currently unknown. Here, a new amplicon analysis tool, the Parallel Amplicon Sequencing Error Correction (PASEC) pipeline, is used to evaluate the performance of amplicon sequencing on low-density Plasmodium DNA samples. Illumina-based sequencing of two Plasmodium falciparum genomic regions (CSP and SERA2) was performed on two types of samples: in vitro DNA mixtures mimicking low-density infections (1–200 genomes/μl) and extracted blood spots from a combination of symptomatic and asymptomatic individuals (44–653,080 parasites/μl). Three additional analysis tools—DADA2, HaplotypR, and SeekDeep—were applied to both datasets and the precision and sensitivity of each tool were evaluated. Results Amplicon sequencing can contend with low-density samples, showing reasonable detection accuracy down to a concentration of 5 Plasmodium genomes/μl. Due to increased stochasticity and background noise, however, all four tools showed reduced sensitivity and precision on samples with very low parasitaemia (< 5 copies/μl) or low read count (< 100 reads per amplicon). PASEC could distinguish major from minor haplotypes with an accuracy of 90% in samples with at least 30 Plasmodium genomes/μl, but only 61% at low Plasmodium concentrations (< 5 genomes/μl) and 46% at very low read counts (< 25 reads per amplicon). The four tools were additionally used on a panel of extracted parasite-positive blood spots from natural malaria infections. While all four identified concordant patterns of complexity of infection (COI) across four sub-Saharan African countries, COI values obtained for individual samples differed in some cases. Conclusions Amplicon deep sequencing can be used to determine the complexity and diversity of low-density Plasmodium infections. Despite differences in their approach, four state-of-the-art tools resolved known haplotype mixtures with similar sensitivity and precision. Researchers can therefore choose from multiple robust approaches for analysing amplicon data, however, error filtration approaches should not be uniformly applied across samples of varying parasitaemia. Samples with very low parasitaemia and very low read count have higher false positive rates and call for read count thresholds that are higher than current default recommendations.
    Keywords Targeted amplicon deep sequencing ; Haplotype calling ; Multiplicity of infection ; Multiclonal infection ; Within-host diversity ; Molecular epidemiology ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
    Subject code 500
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Real-time Metagenomic Analysis of Undiagnosed Fever Cases Unveils a Yellow Fever Outbreak in Edo State, Nigeria

    Fehintola V. Ajogbasile / Judith U. Oguzie / Paul E. Oluniyi / Philomena E. Eromon / Jessica N. Uwanibe / Samar B. Mehta / Katherine J. Siddle / Ikponmwosa Odia / Sarah M. Winnicki / Nosa Akpede / George Akpede / Sylvanus Okogbenin / Ephraim Ogbaini-Emovon / Bronwyn L. MacInnis / Onikepe A. Folarin / Kayvon Modjarrad / Stephen F. Schaffner / Oyewale Tomori / Chikwe Ihekweazu /
    Pardis C. Sabeti / Christian T. Happi

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 6

    Abstract: Abstract Fifty patients with unexplained fever and poor outcomes presented at Irrua Specialist Teaching Hospital (ISTH) in Edo State, Nigeria, an area endemic for Lassa fever, between September 2018 - January 2019. After ruling out Lassa fever, plasma ... ...

    Abstract Abstract Fifty patients with unexplained fever and poor outcomes presented at Irrua Specialist Teaching Hospital (ISTH) in Edo State, Nigeria, an area endemic for Lassa fever, between September 2018 - January 2019. After ruling out Lassa fever, plasma samples from these epidemiologically-linked cases were sent to the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer’s University, Ede, Osun State, Nigeria, where we carried out metagenomic sequencing which implicated yellow fever virus (YFV) as the etiology of this outbreak. Twenty-nine of the 50 samples were confirmed positive for YFV by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), 14 of which resulted in genome assembly. Maximum likelihood phylogenetic analysis revealed that these YFV sequences formed a tightly clustered clade more closely related to sequences from Senegal than sequences from earlier Nigerian isolates, suggesting that the YFV clade responsible for this outbreak in Edo State does not descend directly from the Nigerian YFV outbreaks of the last century, but instead reflects a broader diversity and dynamics of YFV in West Africa. Here we demonstrate the power of metagenomic sequencing for identifying ongoing outbreaks and their etiologies and informing real-time public health responses, resulting in accurate and prompt disease management and control.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Streamlined inactivation, amplification, and Cas13-based detection of SARS-CoV-2

    Jon Arizti-Sanz / Catherine A. Freije / Alexandra C. Stanton / Brittany A. Petros / Chloe K. Boehm / Sameed Siddiqui / Bennett M. Shaw / Gordon Adams / Tinna-Solveig F. Kosoko-Thoroddsen / Molly E. Kemball / Jessica N. Uwanibe / Fehintola V. Ajogbasile / Philomena E. Eromon / Robin Gross / Loni Wronka / Katie Caviness / Lisa E. Hensley / Nicholas H. Bergman / Bronwyn L. MacInnis /
    Christian T. Happi / Jacob E. Lemieux / Pardis C. Sabeti / Cameron Myhrvold

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 9

    Abstract: The COVID-19 pandemic has highlighted the need for user-friendly diagnostic techniques. Here, the authors present SHINE, a streamlined and optimised Cas13-based method with accompanying smartphone app for visual diagnosis. ...

    Abstract The COVID-19 pandemic has highlighted the need for user-friendly diagnostic techniques. Here, the authors present SHINE, a streamlined and optimised Cas13-based method with accompanying smartphone app for visual diagnosis.
    Keywords Science ; Q
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  5. Article ; Online: Combining genomics and epidemiology to track mumps virus transmission in the United States.

    Shirlee Wohl / Hayden C Metsky / Stephen F Schaffner / Anne Piantadosi / Meagan Burns / Joseph A Lewnard / Bridget Chak / Lydia A Krasilnikova / Katherine J Siddle / Christian B Matranga / Bettina Bankamp / Scott Hennigan / Brandon Sabina / Elizabeth H Byrne / Rebecca J McNall / Rickey R Shah / James Qu / Daniel J Park / Soheyla Gharib /
    Susan Fitzgerald / Paul Barreira / Stephen Fleming / Susan Lett / Paul A Rota / Lawrence C Madoff / Nathan L Yozwiak / Bronwyn L MacInnis / Sandra Smole / Yonatan H Grad / Pardis C Sabeti

    PLoS Biology, Vol 18, Iss 2, p e

    2020  Volume 3000611

    Abstract: Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. We paired epidemiological data from public health investigations ... ...

    Abstract Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. We paired epidemiological data from public health investigations with analysis of mumps virus whole genome sequences from 201 infected individuals, focusing on Massachusetts university communities. Our analysis suggests continuous, undetected circulation of mumps locally and nationally, including multiple independent introductions into Massachusetts and into individual communities. Despite the presence of these multiple mumps virus lineages, the genomic data show that one lineage has dominated in the US since at least 2006. Widespread transmission was surprising given high vaccination rates, but we found no genetic evidence that variants arising during this outbreak contributed to vaccine escape. Viral genomic data allowed us to reconstruct mumps transmission links not evident from epidemiological data or standard single-gene surveillance efforts and also revealed connections between apparently unrelated mumps outbreaks.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections

    Angela M. Early / Marc Lievens / Bronwyn L. MacInnis / Christian F. Ockenhouse / Sarah K. Volkman / Samuel Adjei / Tsiri Agbenyega / Daniel Ansong / Stacey Gondi / Brian Greenwood / Mary Hamel / Chris Odero / Kephas Otieno / Walter Otieno / Seth Owusu-Agyei / Kwaku Poku Asante / Hermann Sorgho / Lucas Tina / Halidou Tinto /
    Innocent Valea / Dyann F. Wirth / Daniel E. Neafsey

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 10

    Abstract: Host immune responses exert selective pressure on Plasmodium falciparum. Here, the authors show that allele-specific immunity impacts the antigenic diversity of individual malaria infections. This process partially explains the extreme amino acid ... ...

    Abstract Host immune responses exert selective pressure on Plasmodium falciparum. Here, the authors show that allele-specific immunity impacts the antigenic diversity of individual malaria infections. This process partially explains the extreme amino acid diversity of many parasite antigens and suggests that vaccines should account for allele-specific immunity.
    Keywords Science ; Q
    Language English
    Publishing date 2018-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya.

    Jason P Wendler / John Okombo / Roberto Amato / Olivo Miotto / Steven M Kiara / Leah Mwai / Lewa Pole / John O'Brien / Magnus Manske / Dan Alcock / Eleanor Drury / Mandy Sanders / Samuel O Oyola / Cinzia Malangone / Dushyanth Jyothi / Alistair Miles / Kirk A Rockett / Bronwyn L MacInnis / Kevin Marsh /
    Philip Bejon / Alexis Nzila / Dominic P Kwiatkowski

    PLoS ONE, Vol 9, Iss 5, p e

    2014  Volume 96486

    Abstract: Drug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested the genome-wide associations (GWA) of sequence-based genotypes from 35 Kenyan P. falciparum parasites with the ... ...

    Abstract Drug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested the genome-wide associations (GWA) of sequence-based genotypes from 35 Kenyan P. falciparum parasites with the activities of 22 antimalarial drugs.Parasites isolated from children with acute febrile malaria were adapted to culture, and sensitivity was determined by in vitro growth in the presence of anti-malarial drugs. Parasites were genotyped using whole genome sequencing techniques. Associations between 6250 single nucleotide polymorphisms (SNPs) and resistance to individual anti-malarial agents were determined, with false discovery rate adjustment for multiple hypothesis testing. We identified expected associations in the pfcrt region with chloroquine (CQ) activity, and other novel loci associated with amodiaquine, quinazoline, and quinine activities. Signals for CQ and primaquine (PQ) overlap in and around pfcrt, and interestingly the phenotypes are inversely related for these two drugs. We catalog the variation in dhfr, dhps, mdr1, nhe, and crt, including novel SNPs, and confirm the presence of a dhfr-164L quadruple mutant in coastal Kenya. Mutations implicated in sulfadoxine-pyrimethamine resistance are at or near fixation in this sample set.Sequence-based GWA studies are powerful tools for phenotypic association tests. Using this approach on falciparum parasites from coastal Kenya we identified known and previously unreported genes associated with phenotypic resistance to anti-malarial drugs, and observe in high-resolution haplotype visualizations a possible signature of an inverse selective relationship between CQ and PQ.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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