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  1. Article ; Online: Who Lives, Who Dies, Who Tells Your Story?

    Duggal, Priya

    The Journal of infectious diseases

    2023  Volume 228, Issue 7, Page(s) 811–813

    Language English
    Publishing date 2023-07-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiad201
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  2. Article: Identity by descent mapping of HCV spontaneous clearance in populations of diverse ancestry.

    Yu, Zixuan / Abdel-Azim, Salma / Duggal, Priya / Vergara, Candelaria

    Research square

    2023  

    Abstract: Background: Acute infection with hepatitis C virus (HCV) affects millions of individuals worldwide. Host genetics plays a role in spontaneous clearance of the acute infection which occurs in approximately 30% of the individuals. Common variants in : ... ...

    Abstract Background: Acute infection with hepatitis C virus (HCV) affects millions of individuals worldwide. Host genetics plays a role in spontaneous clearance of the acute infection which occurs in approximately 30% of the individuals. Common variants in
    Results: We detected 1,711,832 and 5,678,043 and individual pairs of IBD segments in the European and African ancestry individuals, respectively. As expected, individuals of African descent had more, and shorter segments compared to Europeans. We did not detect any significant IBD signals in the known associated gene regions.
    Conclusions: IBD is based on sharing of haplotypes and is most powerful in populations with a shared founder or recent common ancestor. For the complex trait of HCV clearance, we used two outbred, global populations that limited our power to detect IBD associations. Overall, in this population-based sample we failed to detect rare variations associated with HCV clearance in individuals of European and African ancestry.
    Language English
    Publishing date 2023-01-09
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-2433454/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Defining representativeness of study samples in medical and population health research.

    Rudolph, Jacqueline E / Zhong, Yongqi / Duggal, Priya / Mehta, Shruti H / Lau, Bryan

    BMJ medicine

    2023  Volume 2, Issue 1, Page(s) e000399

    Abstract: Medical and population health science researchers frequently make ambiguous statements about whether they believe their study sample or results are representative of some (implicit or explicit) target population. This article provides a comprehensive ... ...

    Abstract Medical and population health science researchers frequently make ambiguous statements about whether they believe their study sample or results are representative of some (implicit or explicit) target population. This article provides a comprehensive definition of representativeness, with the goal of capturing the different ways in which a study can be representative of a target population. It is proposed that a study is representative if the estimate obtained in the study sample is generalisable to the target population (owing to representative sampling, estimation of stratum specific effects, or quantitative methods to generalise or transport estimates) or the interpretation of the results is generalisable to the target population (based on fundamental scientific premises and substantive background knowledge). This definition is explored in the context of four covid-19 studies, ranging from laboratory science to descriptive epidemiology. All statements regarding representativeness should make clear the way in which the study results generalise, the target population the results are being generalised to, and the assumptions that must hold for that generalisation to be scientifically or statistically justifiable.
    Language English
    Publishing date 2023-05-16
    Publishing country England
    Document type Journal Article
    ISSN 2754-0413
    ISSN (online) 2754-0413
    DOI 10.1136/bmjmed-2022-000399
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  4. Article ; Online: A hepatitis B virus (HBV) sequence variation graph improves alignment and sample-specific consensus sequence construction.

    Duchen, Dylan / Clipman, Steven J / Vergara, Candelaria / Thio, Chloe L / Thomas, David L / Duggal, Priya / Wojcik, Genevieve L

    PloS one

    2024  Volume 19, Issue 4, Page(s) e0301069

    Abstract: Nearly 300 million individuals live with chronic hepatitis B virus (HBV) infection (CHB), for which no curative therapy is available. As viral diversity is associated with pathogenesis and immunological control of infection, improved methods to ... ...

    Abstract Nearly 300 million individuals live with chronic hepatitis B virus (HBV) infection (CHB), for which no curative therapy is available. As viral diversity is associated with pathogenesis and immunological control of infection, improved methods to characterize this diversity could aid drug development efforts. Conventionally, viral sequencing data are mapped/aligned to a reference genome, and only the aligned sequences are retained for analysis. Thus, reference selection is critical, yet selecting the most representative reference a priori remains difficult. We investigate an alternative pangenome approach which can combine multiple reference sequences into a graph which can be used during alignment. Using simulated short-read sequencing data generated from publicly available HBV genomes and real sequencing data from an individual living with CHB, we demonstrate alignment to a phylogenetically representative 'genome graph' can improve alignment, avoid issues of reference ambiguity, and facilitate the construction of sample-specific consensus sequences more genetically similar to the individual's infection. Graph-based methods can, therefore, improve efforts to characterize the genetics of viral pathogens, including HBV, and have broader implications in host-pathogen research.
    MeSH term(s) Hepatitis B virus/genetics ; Humans ; Genome, Viral ; Consensus Sequence/genetics ; Phylogeny ; Sequence Alignment/methods ; Genetic Variation ; Hepatitis B, Chronic/virology ; DNA, Viral/genetics ; Sequence Analysis, DNA/methods
    Chemical Substances DNA, Viral
    Language English
    Publishing date 2024-04-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0301069
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  5. Article ; Online: Correction: Enterovirus D68 molecular and cellular biology and pathogenesis.

    Elrick, Matthew J / Pekosz, Andrew / Duggal, Priya

    The Journal of biological chemistry

    2021  Volume 296, Page(s) 100587

    Language English
    Publishing date 2021-04-09
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2021.100587
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  6. Article ; Online: Enterovirus D68 molecular and cellular biology and pathogenesis.

    Elrick, Matthew J / Pekosz, Andrew / Duggal, Priya

    The Journal of biological chemistry

    2021  Volume 296, Page(s) 100317

    Abstract: In recent years, enterovirus D68 (EV-D68) has advanced from a rarely detected respiratory virus to a widespread pathogen responsible for increasing rates of severe respiratory illness and acute flaccid myelitis (AFM) in children worldwide. In this review, ...

    Abstract In recent years, enterovirus D68 (EV-D68) has advanced from a rarely detected respiratory virus to a widespread pathogen responsible for increasing rates of severe respiratory illness and acute flaccid myelitis (AFM) in children worldwide. In this review, we discuss the accumulating data on the molecular features of EV-D68 and place these into the context of enterovirus biology in general. We highlight similarities and differences with other enteroviruses and genetic divergence from own historical prototype strains of EV-D68. These include changes in capsid antigens, host cell receptor usage, and viral RNA metabolism collectively leading to increased virulence. Furthermore, we discuss the impact of EV-D68 infection on the biology of its host cells, and how these changes are hypothesized to contribute to motor neuron toxicity in AFM. We highlight areas in need of further research, including the identification of its primary receptor and an understanding of the pathogenic cascade leading to motor neuron injury in AFM. Finally, we discuss the epidemiology of the EV-D68 and potential therapeutic approaches.
    MeSH term(s) Central Nervous System Viral Diseases/epidemiology ; Central Nervous System Viral Diseases/virology ; Enterovirus D, Human/classification ; Enterovirus D, Human/genetics ; Enterovirus D, Human/pathogenicity ; Enterovirus Infections/epidemiology ; Enterovirus Infections/virology ; Humans ; Myelitis/epidemiology ; Myelitis/virology ; Neuromuscular Diseases/epidemiology ; Neuromuscular Diseases/virology ; Phylogeny
    Language English
    Publishing date 2021-01-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2021.100317
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  7. Article ; Online: Does Malnutrition Have a Genetic Component?

    Duggal, Priya / Petri, William A

    Annual review of genomics and human genetics

    2018  Volume 19, Page(s) 247–262

    Abstract: Malnutrition is a complex disorder, defined by an imbalance, excess, or deficiency of nutrient intake. The visible signs of malnutrition are stunted growth and wasting, but malnourished children are also more likely to have delays in neurocognitive ... ...

    Abstract Malnutrition is a complex disorder, defined by an imbalance, excess, or deficiency of nutrient intake. The visible signs of malnutrition are stunted growth and wasting, but malnourished children are also more likely to have delays in neurocognitive development, vaccine failure, and susceptibility to infection. Despite malnutrition being a major global health problem, we do not yet understand the pathogenesis of this complex disorder. Although lack of food is a major contributor to childhood malnutrition, it is not the sole cause. The mother's prenatal nutritional status, enteric infections, and intestinal inflammation also contribute to the risk of childhood malnutrition and recovery. Here, we discuss another potential risk factor, host and maternal genetics, that may play a role in the risk of malnutrition via several biological pathways. Understanding the genetic risks of malnutrition may help to identify ideal targets for intervention and treatment of malnutrition.
    MeSH term(s) Child ; Child Nutrition Disorders/epidemiology ; Child Nutrition Disorders/genetics ; Genetic Predisposition to Disease ; Growth ; Humans ; Malnutrition/epidemiology ; Malnutrition/genetics ; Prevalence
    Language English
    Publishing date 2018-06-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2037670-4
    ISSN 1545-293X ; 1527-8204
    ISSN (online) 1545-293X
    ISSN 1527-8204
    DOI 10.1146/annurev-genom-083117-021340
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  8. Article ; Online: Obesity could shift severe COVID-19 disease to younger ages.

    Kass, David A / Duggal, Priya / Cingolani, Oscar

    Lancet (London, England)

    2020  Volume 395, Issue 10236, Page(s) 1544–1545

    MeSH term(s) Adult ; Age Factors ; Aged ; Body Mass Index ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Obesity/complications ; Obesity/epidemiology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/epidemiology ; Risk Factors
    Keywords covid19
    Language English
    Publishing date 2020-05-04
    Publishing country England
    Document type Letter
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(20)31024-2
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  9. Article ; Online: Multiancestry sex-stratified genomic associations with HIV viral load and controller status from the ICGH.

    Vergara, Candelaria / Tuff, Jeffrey F / Fellay, Jacques / Duggal, Priya / Scully, Eileen P / McLaren, Paul J

    JCI insight

    2023  Volume 8, Issue 11

    Abstract: Biological sex and host genetics influence HIV pathogenesis. Females have a higher likelihood of spontaneous viral control and lower set point viral load (spVL). No prior studies have assessed sex-specific genetics of HIV. To address this, we performed a ...

    Abstract Biological sex and host genetics influence HIV pathogenesis. Females have a higher likelihood of spontaneous viral control and lower set point viral load (spVL). No prior studies have assessed sex-specific genetics of HIV. To address this, we performed a sex-stratified genome-wide association study using data from the ICGH. Although it is the largest collection of genomic data in HIV, this multiethnic sample of 9,705 people is 81.3% male. We sought to identify sex-specific genetic variants and genes associated with HIV spVL and control. We confirmed associations in the HLA and CCR5 regions in males and HLA in females. Gene-based analyses detected associations between HIV spVL and PET100, PCP2, XAB2, and STXBP2 only in males. We detected variants with a significant sex-differential effect on spVL in SDC3 and PUM1 (rs10914268) and PSORS1C2 (rs1265159) and on HIV control in SUB1 (rs687659), AL158151.3, PTPA, and IER5L (rs4387067). Those variants have epigenetic and genetic interactions with relevant genes with both cis and trans effects. In summary, we identified sex-shared associations at the single-variant level, sex-specific associations at the gene-based level, and genetic variants with significant differential effects between the sexes.
    MeSH term(s) Female ; Humans ; Male ; HIV Infections/genetics ; HIV-1/genetics ; Viral Load/genetics ; Genome-Wide Association Study ; Genomics ; RNA-Binding Proteins/genetics
    Chemical Substances PUM1 protein, human ; RNA-Binding Proteins
    Language English
    Publishing date 2023-06-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.170068
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  10. Article: A hepatitis B virus (HBV) sequence variation graph improves sequence alignment and sample-specific consensus sequence construction for genetic analysis of HBV.

    Duchen, Dylan / Clipman, Steven / Vergara, Candelaria / Thio, Chloe L / Thomas, David L / Duggal, Priya / Wojcik, Genevieve L

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Hepatitis B virus (HBV) remains a global public health concern, with over 250 million individuals living with chronic HBV infection (CHB) and no curative therapy currently available. Viral diversity is associated with CHB pathogenesis and immunological ... ...

    Abstract Hepatitis B virus (HBV) remains a global public health concern, with over 250 million individuals living with chronic HBV infection (CHB) and no curative therapy currently available. Viral diversity is associated with CHB pathogenesis and immunological control of infection. Improved methods to characterize the viral genome at both the population and intra-host level could aid drug development efforts. Conventionally, HBV sequencing data are aligned to a linear reference genome and only sequences capable of aligning to the reference are captured for analysis. Reference selection has additional consequences, including sample-specific 'consensus' sequence construction. It remains unclear how to select a reference from available sequences and whether a single reference is sufficient for genetic analyses. Using simulated short-read sequencing data generated from full-length publicly available HBV genome sequences and HBV sequencing data from a longitudinally sampled individual with CHB, we investigate alternative graph-based alignment approaches. We demonstrate that using a phylogenetically representative 'genome graph' for alignment, rather than linear reference sequences, avoids issues of reference ambiguity, improves alignment, and facilitates the construction of sample-specific consensus sequences genetically similar to an individual's infection. Graph-based methods can therefore improve efforts to characterize the genetics of viral pathogens, including HBV, and may have broad implications in host pathogen research.
    Language English
    Publishing date 2023-01-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.11.523611
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