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  1. Article ; Online: Locations and structures of influenza A virus packaging-associated signals and other functional elements via an in silico pipeline for predicting constrained features in RNA viruses.

    Beniston, Emma / Skittrall, Jordan P

    PLoS computational biology

    2024  Volume 20, Issue 4, Page(s) e1012009

    Abstract: Influenza A virus contains regions of its segmented genome associated with ability to package the segments into virions, but many such regions are poorly characterised. We provide detailed predictions of the key locations within these packaging- ... ...

    Abstract Influenza A virus contains regions of its segmented genome associated with ability to package the segments into virions, but many such regions are poorly characterised. We provide detailed predictions of the key locations within these packaging-associated regions, and their structures, by applying a recently-improved pipeline for delineating constrained regions in RNA viruses and applying structural prediction algorithms. We find and characterise other known constrained regions within influenza A genomes, including the region associated with the PA-X frameshift, regions associated with alternative splicing, and constraint around the initiation motif for a truncated PB1 protein, PB1-N92, associated with avian viruses. We further predict the presence of constrained regions that have not previously been described. The extra characterisation our work provides allows investigation of these key regions for drug target potential, and points towards determinants of packaging compatibility between segments.
    Language English
    Publishing date 2024-04-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1012009
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  2. Article ; Online: SARS-CoV-2 screening: effectiveness and risk of increasing transmission.

    Skittrall, Jordan P

    Journal of the Royal Society, Interface

    2021  Volume 18, Issue 180, Page(s) 20210164

    Abstract: Testing asymptomatic people for SARS-CoV-2 aims to reduce COVID-19 transmission. Screening programmes' effectiveness depends upon testing strategy, sample handling logistics, test sensitivity and individual behaviour, in addition to dynamics of viral ... ...

    Abstract Testing asymptomatic people for SARS-CoV-2 aims to reduce COVID-19 transmission. Screening programmes' effectiveness depends upon testing strategy, sample handling logistics, test sensitivity and individual behaviour, in addition to dynamics of viral transmission. The interaction between these factors is not fully characterized. We investigated the interaction between these factors to determine how to optimize reduction of transmission. We estimate that under idealistic assumptions 70% of transmission may be averted, but under realistic assumptions only 7% may be averted. We show that programmes that overwhelm laboratory capacity or reduce isolation of those with minor symptoms have increased transmission compared with those that do not: programmes need to be designed to avoid these issues, or they will be ineffective or even counter-productive. Our model allows optimal selection of whom to test, quantifies the balance between accuracy and timeliness, and quantifies potential impacts of behavioural interventions. We anticipate our model can be used to understand optimal screening strategies for other infectious diseases with substantially different dynamics.
    MeSH term(s) COVID-19 ; COVID-19 Testing ; Humans ; SARS-CoV-2
    Language English
    Publishing date 2021-07-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2156283-0
    ISSN 1742-5662 ; 1742-5689
    ISSN (online) 1742-5662
    ISSN 1742-5689
    DOI 10.1098/rsif.2021.0164
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  3. Article ; Online: Serology versus nucleic acid amplification to diagnose acute hepatitis E, United Kingdom, 2014-18.

    Skittrall, Jordan P / Jalal, Hamid

    The Journal of infection

    2022  Volume 85, Issue 3, Page(s) 327–333

    Abstract: ... U test, p = 0.14).: Conclusions: In immunocompetent patients, tests beyond IgM seldom add ...

    Abstract Objectives: Diagnosing hepatitis E infection usually involves specific IgM testing, but sensitivity/specificity concerns mean many guidelines and practices include confirmatory tests. We studied whether additional information confirmatory tests provide justifies their use.
    Methods: We examined 9131 records of anti-hepatitis E IgM assays, 7615 of IgG assays, and 1726 of RT-PCR assays from our regional laboratory, spanning October 2014-October 2018. We paired 495 IgM assay results with a RT-PCR result. We examined whether IgM results predicted PCR results, reviewed discrepant pairs, and investigated the correlation between IgG and PCR results in patients with strongly reactive IgM assays.
    Results: Anti-hepatitis E IgM titres are bimodal. A high cut-off value optimises prediction of RNA detectability. 7/404 low-IgM samples had detectable RNA, 6 from immunosuppressed patients. 26/91 high-IgM samples did not have detectable RNA. In high-IgM samples, RNA detectability was not associated with IgG titre (one-tailed Mann-Whitney U test, p = 0.14).
    Conclusions: In immunocompetent patients, tests beyond IgM seldom add clinically useful information. In patients with immunocompromise, IgM and RNA could contribute information. Additional tests' extra costs/intervention delays cannot be justified. IgM assay cut-offs should reflect titres' bimodal distribution, with values standardised using international units.
    MeSH term(s) Hepatitis Antibodies ; Hepatitis E/diagnosis ; Hepatitis E virus/genetics ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Nucleic Acids ; RNA ; RNA, Viral
    Chemical Substances Hepatitis Antibodies ; Immunoglobulin G ; Immunoglobulin M ; Nucleic Acids ; RNA, Viral ; RNA (63231-63-0)
    Language English
    Publishing date 2022-06-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 424417-5
    ISSN 1532-2742 ; 0163-4453
    ISSN (online) 1532-2742
    ISSN 0163-4453
    DOI 10.1016/j.jinf.2022.06.017
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  4. Article ; Online: Asymptomatic SARS-CoV-2 testing: predictors of effectiveness; risk of increasing transmission

    Skittrall, Jordan P

    medRxiv

    Abstract: Testing asymptomatic people for SARS-CoV-2 aims to reduce COVID-19 transmission. Screening programs9 effectiveness depends upon testing strategy, sample handling logistics, test sensitivity, and individual behavior, in addition to dynamics of viral ... ...

    Abstract Testing asymptomatic people for SARS-CoV-2 aims to reduce COVID-19 transmission. Screening programs9 effectiveness depends upon testing strategy, sample handling logistics, test sensitivity, and individual behavior, in addition to dynamics of viral transmission. We investigated the interaction between these factors to determine how to optimize reduction of transmission. We show that under idealistic assumptions 70% of transmission may be averted, but under realistic assumptions only 7% may be averted. We show that programs that overwhelm laboratory capacity or reduce isolation of those with minor symptoms have increased transmission compared with those that do not: programs need to be designed to avoid these issues. Our model allows optimal selection of whom to test, quantifies the balance between accuracy and timeliness, and quantifies potential impacts of behavioral interventions.
    Keywords covid19
    Language English
    Publishing date 2020-11-24
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.11.24.20236950
    Database COVID19

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  5. Article ; Online: A novel approach to finding conserved features in low-variability gene alignments characterises RNA motifs in SARS-CoV and SARS-CoV-2.

    Skittrall, Jordan P / Irigoyen, Nerea / Brierley, Ian / Gog, Julia R

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 12079

    Abstract: Collections of genetic sequences belonging to related organisms contain information on the evolutionary constraints to which the organisms have been subjected. Heavily constrained regions can be investigated to understand their roles in an organism's ... ...

    Abstract Collections of genetic sequences belonging to related organisms contain information on the evolutionary constraints to which the organisms have been subjected. Heavily constrained regions can be investigated to understand their roles in an organism's life cycle, and drugs can be sought to disrupt these roles. In organisms with low genetic diversity, such as newly-emerged pathogens, it is key to obtain this information early to develop new treatments. Here, we present methods that ensure we can leverage all the information available in a low-signal, low-noise set of sequences, to find contiguous regions of relatively conserved nucleic acid. We demonstrate the application of these methods by analysing over 5 million genome sequences of the recently-emerged RNA virus SARS-CoV-2 and correlating these results with an analysis of 119 genome sequences of SARS-CoV. We propose the precise location of a previously described packaging signal, and discuss explanations for other regions of high conservation.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; COVID-19/genetics ; Nucleotide Motifs ; Sequence Alignment ; Genome, Viral ; Severe acute respiratory syndrome-related coronavirus/genetics
    Language English
    Publishing date 2023-07-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-39207-1
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  6. Article ; Online: Preparing for the next pandemic: reserve laboratory staff are crucial.

    Skittrall, Jordan P / Bentley, Neil / Wreghitt, Tim / Silverston, Paul / Yang, Huina / Aliyu, Sani H / Smielewska, Anna A

    BMJ (Clinical research ed.)

    2022  Volume 378, Page(s) e072467

    MeSH term(s) Disease Outbreaks ; Humans ; Influenza, Human/epidemiology ; Laboratories ; Pandemics/prevention & control
    Language English
    Publishing date 2022-09-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 1362901-3
    ISSN 1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    ISSN (online) 1756-1833
    ISSN 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    DOI 10.1136/bmj-2022-072467
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  7. Article ; Online: A new method for detecting signal regions in ordered sequences of real numbers, and application to viral genomic data.

    Gog, Julia R / Lever, Andrew M L / Skittrall, Jordan P

    PloS one

    2018  Volume 13, Issue 4, Page(s) e0195763

    Abstract: We present a fast, robust and parsimonious approach to detecting signals in an ordered sequence of numbers. Our motivation is in seeking a suitable method to take a sequence of scores corresponding to properties of positions in virus genomes, and find ... ...

    Abstract We present a fast, robust and parsimonious approach to detecting signals in an ordered sequence of numbers. Our motivation is in seeking a suitable method to take a sequence of scores corresponding to properties of positions in virus genomes, and find outlying regions of low scores. Suitable statistical methods without using complex models or making many assumptions are surprisingly lacking. We resolve this by developing a method that detects regions of low score within sequences of real numbers. The method makes no assumptions a priori about the length of such a region; it gives the explicit location of the region and scores it statistically. It does not use detailed mechanistic models so the method is fast and will be useful in a wide range of applications. We present our approach in detail, and test it on simulated sequences. We show that it is robust to a wide range of signal morphologies, and that it is able to capture multiple signals in the same sequence. Finally we apply it to viral genomic data to identify regions of evolutionary conservation within influenza and rotavirus.
    MeSH term(s) Algorithms ; Biological Evolution ; Computational Biology/methods ; Computer Simulation ; Databases, Genetic ; Genetic Variation ; Genome, Viral ; Genomics/methods ; Humans
    Language English
    Publishing date 2018
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0195763
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  8. Article ; Online: Multiplex MinION sequencing suggests enteric adenovirus F41 genetic diversity comparable to pre-COVID-19 era.

    Maes, Mailis / Khokhar, Fahad / Wilkinson, Sam A J / Smith, Andrew D / Kovalenko, Ganna / Dougan, Gordon / Quick, Joshua / Loman, Nicholas J / Baker, Stephen / Curran, Martin D / Skittrall, Jordan P / Houldcroft, Charlotte J

    Microbial genomics

    2023  Volume 9, Issue 1

    Abstract: Human adenovirus F41 causes acute gastroenteritis in children, and has recently been associated with an apparent increase in paediatric hepatitis of unknown aetiology in the UK, with further cases reported in multiple countries. Relatively little is ... ...

    Abstract Human adenovirus F41 causes acute gastroenteritis in children, and has recently been associated with an apparent increase in paediatric hepatitis of unknown aetiology in the UK, with further cases reported in multiple countries. Relatively little is known about the genetic diversity of adenovirus F41 in UK children; and it is unclear what, if any, impact the COVID-19 pandemic has had on viral diversity in the UK. Methods that allow F41 to be sequenced from clinical samples without the need for viral culture are required to provide the genomic data to address these questions. Therefore, we evaluated an overlapping-amplicon method of sequencing adenovirus genomes from clinical samples using Oxford Nanopore technology. We applied this method to a small sample of adenovirus-species-F-positive extracts collected as part of standard care in the East of England region in January-May 2022. This method produced genomes with >75 % coverage in 13/22 samples and >50 % coverage in 19/22 samples. We identified two F41 lineages present in paediatric patients in the East of England in 2022. Where F41 genomes from paediatric hepatitis cases were available (
    MeSH term(s) Humans ; Child ; COVID-19/epidemiology ; Pandemics ; Sequence Analysis ; Adenoviridae/genetics ; Adenoviridae Infections ; Genetic Variation
    Language English
    Publishing date 2023-05-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2835258-0
    ISSN 2057-5858 ; 2057-5858
    ISSN (online) 2057-5858
    ISSN 2057-5858
    DOI 10.1099/mgen.0.000920
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  9. Article ; Online: The changing face of bacteraemia in an HIV-1 positive cohort in the United Kingdom.

    Bryce, Aliya N / Skittrall, Jordan P / Gilleece, Yvonne / Sargent, Catherine

    The Journal of infection

    2017  Volume 74, Issue 3, Page(s) 325–328

    MeSH term(s) Bacteremia ; Cohort Studies ; HIV-1 ; Humans ; United Kingdom
    Language English
    Publishing date 2017
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 424417-5
    ISSN 1532-2742 ; 0163-4453
    ISSN (online) 1532-2742
    ISSN 0163-4453
    DOI 10.1016/j.jinf.2016.12.014
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  10. Article ; Online: Diagnostic tool or screening programme? Asymptomatic testing for SARS-CoV-2 needs clear goals and protocols.

    Skittrall, Jordan P / Fortune, Mary D / Jalal, Hamid / Zhang, Hongyi / Enoch, David A / Brown, Nicholas M / Swift, Anne

    The Lancet regional health. Europe

    2020  Volume 1, Page(s) 100002

    Language English
    Publishing date 2020-12-15
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2666-7762
    ISSN (online) 2666-7762
    DOI 10.1016/j.lanepe.2020.100002
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