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  1. AU="Giroux, Nicholas S"
  2. AU="Carmen Avila-Casado"
  3. AU=Coke Christopher J.
  4. AU="Nascimento, José Hamilton do"
  5. AU="Parel, Philip M"
  6. AU="Sandrine Barbaux"
  7. AU="Sarkar, S."
  8. AU="Maymi, Valerie"
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  1. Article ; Online: Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection.

    McClain, Micah T / Zhbannikov, Ilya / Satterwhite, Lisa L / Henao, Ricardo / Giroux, Nicholas S / Ding, Shengli / Burke, Thomas W / Tsalik, Ephraim L / Nix, Christina / Balcazar, Jorge Prado / Petzold, Elizabeth A / Shen, Xiling / Woods, Christopher W

    iScience

    2023  Volume 27, Issue 1, Page(s) 108288

    Abstract: To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined ... ...

    Abstract To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) at admission and compared subjects who improved from their moderate disease with those who later clinically decompensated and required invasive mechanical ventilation or died. Chromatin accessibility and transcriptomic immune profiles were markedly altered between the two groups, with strong signals in CD4
    Language English
    Publishing date 2023-11-29
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.108288
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Author Correction: Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.

    Giroux, Nicholas S / Ding, Shengli / McClain, Micah T / Burke, Thomas W / Petzold, Elizabeth / Chung, Hong A / Rivera, Grecia O / Wang, Ergang / Xi, Rui / Bose, Shree / Rotstein, Tomer / Nicholson, Bradly P / Chen, Tianyi / Henao, Ricardo / Sempowski, Gregory D / Denny, Thomas N / De Ussel, Maria Iglesias / Satterwhite, Lisa L / Ko, Emily R /
    Ginsburg, Geoffrey S / Kraft, Bryan D / Tsalik, Ephraim L / Shen, Xiling / Woods, Christopher W

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 6462

    Language English
    Publishing date 2023-04-20
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-33323-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: fastMitoCalc: an ultra-fast program to estimate mitochondrial DNA copy number from whole-genome sequences

    Qian, Yong / Butler, Thomas J / Opsahl-Ong, Krista / Giroux, Nicholas S / Sidore, Carlo / Nagaraja, Ramaiah / Cucca, Francesco / Ferrucci, Luigi / Abecasis, Gonçalo R / Schlessinger, David / Ding, Jun

    Bioinformatics. 2017 May 01, v. 33, no. 9

    2017  

    Abstract: Mitochondrial DNA (mtDNA) copy number is tightly regulated in tissues, and is both a critical determinant of mitochondrial function and a potential biomarker for disease. We and other groups have shown that the mtDNA copy number per cell can be directly ... ...

    Abstract Mitochondrial DNA (mtDNA) copy number is tightly regulated in tissues, and is both a critical determinant of mitochondrial function and a potential biomarker for disease. We and other groups have shown that the mtDNA copy number per cell can be directly estimated from whole-genome sequencing. The computation is based on the rationale that sequencing coverage should be proportional to the underlying DNA copy number for autosomal and mitochondrial DNA, and most computing time is spent calculating the average autosomal DNA coverage across ∼3 billion bases. That makes analyzing tens of thousands of available samples very slow. Here we present fastMitoCalc, which takes advantage of the indexing of sequencing alignment files and uses a randomly selected small subset (0.1%) of the nuclear genome to estimate autosomal DNA coverage accurately. It is more than 100 times faster than current programs. fastMitoCalc also provides an option to estimate copy number using a single autosomal chromosome, which could also achieve high accuracy but is slower. Using fastMitoCalc, it becomes much more feasible now to conduct analyses on large-scale consortium data to test for association of mtDNA copy number with quantitative traits or nuclear variants. Availability and Implementation: fastMitoCalc is available at https://lgsun.irp.nia.nih.gov/hsgu/software/mitoAnalyzer/index.html Contact: jun.ding@nih.gov Supplementary information: Supplementary data are available at Bioinformatics online.
    Keywords bioinformatics ; biomarkers ; chromosomes ; mitochondria ; mitochondrial DNA ; nuclear genome ; quantitative traits ; sequence analysis ; tissues
    Language English
    Dates of publication 2017-0501
    Size p. 1399-1401.
    Publishing place Oxford University Press
    Document type Article
    ZDB-ID 1468345-3
    ISSN 1460-2059 ; 1367-4811 ; 1367-4803
    ISSN (online) 1460-2059 ; 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btw835
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Mucosal-associated invariant T cell responses differ by sex in COVID-19.

    Yu, Chen / Littleton, Sejiro / Giroux, Nicholas S / Mathew, Rose / Ding, Shengli / Kalnitsky, Joan / Yang, Yuchen / Petzold, Elizabeth / Chung, Hong A / Rivera, Grecia O / Rotstein, Tomer / Xi, Rui / Ko, Emily R / Tsalik, Ephraim L / Sempowski, Gregory D / Denny, Thomas N / Burke, Thomas W / McClain, Micah T / Woods, Christopher W /
    Shen, Xiling / Saban, Daniel R

    Med (New York, N.Y.)

    2021  Volume 2, Issue 6, Page(s) 755–772.e5

    Abstract: Background: Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, but the mechanisms governing this disparity remain incompletely understood.: Methods: We carried out sex-balanced sampling of peripheral ... ...

    Abstract Background: Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, but the mechanisms governing this disparity remain incompletely understood.
    Methods: We carried out sex-balanced sampling of peripheral blood mononuclear cells from hospitalized and non-hospitalized individuals with confirmed COVID-19, uninfected close contacts, and healthy control individuals for 36-color flow cytometry and single-cell RNA sequencing.
    Findings: Our results revealed a pronounced reduction of circulating mucosal-associated invariant T (MAIT) cells in infected females. Integration of published COVID-19 airway tissue datasets suggests that this reduction represented a major wave of MAIT cell extravasation during early infection in females. Moreover, MAIT cells from females possessed an immunologically active gene signature, whereas cells from males were pro-apoptotic.
    Conclusions: Our findings uncover a female-specific protective MAIT cell profile, potentially shedding light on reduced COVID-19 susceptibility in females.
    Funding: This work was supported by NIH/NIAID (U01AI066569 and UM1AI104681), the Defense Advanced Projects Agency (DARPA; N66001-09-C-2082 and HR0011-17-2-0069), the Veterans Affairs Health System, and Virology Quality Assurance (VQA; 75N93019C00015). The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health. COVID-19 samples were processed under Biosafety level 2 (BSL-2) with aerosol management enhancement or BSL-3 in the Duke Regional Biocontainment Laboratory, which received partial support for construction from NIH/NIAID (UC6AI058607).
    MeSH term(s) COVID-19 ; Female ; Flow Cytometry ; Humans ; Leukocytes, Mononuclear ; Lymphocyte Activation ; Male ; Mucosal-Associated Invariant T Cells ; United States
    Language English
    Publishing date 2021-04-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 2666-6340
    ISSN (online) 2666-6340
    DOI 10.1016/j.medj.2021.04.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.

    Giroux, Nicholas S / Ding, Shengli / McClain, Micah T / Burke, Thomas W / Petzold, Elizabeth / Chung, Hong A / Rivera, Grecia O / Wang, Ergang / Xi, Rui / Bose, Shree / Rotstein, Tomer / Nicholson, Bradly P / Chen, Tianyi / Henao, Ricardo / Sempowski, Gregory D / Denny, Thomas N / De Ussel, Maria Iglesias / Satterwhite, Lisa L / Ko, Emily R /
    Ginsburg, Geoffrey S / Kraft, Bryan D / Tsalik, Ephraim L / Shen, Xiling / Woods, Christopher

    Research square

    2022  

    Abstract: SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein ... ...

    Abstract SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG seroconversion has not been defined. We performed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and RNA-seq on peripheral blood mononuclear cells (PBMCs) from outpatients with mild or moderate symptom severity at different stages of clinical illness. Early in the disease course prior to IgG seroconversion, modifications in chromatin accessibility associate with mild or moderate symptoms are already robust and include severity-associated changes in accessibility of genes in interleukin signaling, regulation of cell differentiation and cell morphology. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif accessibility for individual PBMC cell types over time. The most extensive remodeling occurred in CD14+ monocytes, where sub-populations with distinct chromatin accessibility profiles were observed prior to seroconversion. Mild symptom severity is marked by upregulation classical antiviral pathways including those regulating IRF1 and IRF7, whereas in moderate disease these classical antiviral signals diminish suggesting dysregulated and less effective responses. Together, these observations offer novel insight into the epigenome of early mild SARS-CoV-2 infection and suggest that detection of chromatin remodeling in early disease may offer promise for a new class of diagnostic tools for COVID-19.
    Language English
    Publishing date 2022-04-07
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-1479864/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.

    Giroux, Nicholas S / Ding, Shengli / McClain, Micah T / Burke, Thomas W / Petzold, Elizabeth / Chung, Hong A / Rivera, Grecia O / Wang, Ergang / Xi, Rui / Bose, Shree / Rotstein, Tomer / Nicholson, Bradly P / Chen, Tianyi / Henao, Ricardo / Sempowski, Gregory D / Denny, Thomas N / De Ussel, Maria Iglesias / Satterwhite, Lisa L / Ko, Emily R /
    Ginsburg, Geoffrey S / Kraft, Bryan D / Tsalik, Ephraim L / Shen, Xiling / Woods, Christopher W

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 11714

    Abstract: SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein ... ...

    Abstract SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG seroconversion has not been defined. We performed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and RNA-seq on peripheral blood mononuclear cells (PBMCs) from outpatients with mild or moderate symptom severity at different stages of clinical illness. Early in the disease course prior to IgG seroconversion, modifications in chromatin accessibility associated with mild or moderate symptoms were already robust and included severity-associated changes in accessibility of genes in interleukin signaling, regulation of cell differentiation and cell morphology. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif accessibility for individual PBMC cell types over time. The most extensive remodeling occurred in CD14+ monocytes, where sub-populations with distinct chromatin accessibility profiles were observed prior to seroconversion. Mild symptom severity was marked by upregulation of classical antiviral pathways, including those regulating IRF1 and IRF7, whereas in moderate disease, these classical antiviral signals diminished, suggesting dysregulated and less effective responses. Together, these observations offer novel insight into the epigenome of early mild SARS-CoV-2 infection and suggest that detection of chromatin remodeling in early disease may offer promise for a new class of diagnostic tools for COVID-19.
    MeSH term(s) Antiviral Agents ; COVID-19/genetics ; Chromatin/genetics ; Humans ; Immunoglobulin G/genetics ; Leukocytes, Mononuclear ; SARS-CoV-2 ; Seroconversion ; Severity of Illness Index
    Chemical Substances Antiviral Agents ; Chromatin ; Immunoglobulin G
    Language English
    Publishing date 2022-07-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-15668-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: fastMitoCalc: an ultra-fast program to estimate mitochondrial DNA copy number from whole-genome sequences.

    Qian, Yong / Butler, Thomas J / Opsahl-Ong, Krista / Giroux, Nicholas S / Sidore, Carlo / Nagaraja, Ramaiah / Cucca, Francesco / Ferrucci, Luigi / Abecasis, Gonçalo R / Schlessinger, David / Ding, Jun

    Bioinformatics (Oxford, England)

    2017  

    Language English
    Publishing date 2017-01-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btw835
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: fastMitoCalc: an ultra-fast program to estimate mitochondrial DNA copy number from whole-genome sequences.

    Qian, Yong / Butler, Thomas J / Opsahl-Ong, Krista / Giroux, Nicholas S / Sidore, Carlo / Nagaraja, Ramaiah / Cucca, Francesco / Ferrucci, Luigi / Abecasis, Gonçalo R / Schlessinger, David / Ding, Jun

    Bioinformatics (Oxford, England)

    2017  Volume 33, Issue 9, Page(s) 1399–1401

    Abstract: Availability and implementation: fastMitoCalc is available at https://lgsun.irp.nia.nih.gov/hsgu/software/mitoAnalyzer/index.html.: Contact: jun.ding@nih.gov.: Supplementary information: Supplementary data are available at Bioinformatics online. ...

    Abstract Availability and implementation: fastMitoCalc is available at https://lgsun.irp.nia.nih.gov/hsgu/software/mitoAnalyzer/index.html.
    Contact: jun.ding@nih.gov.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) Gene Dosage ; Genome, Human ; Genome, Mitochondrial ; Genomics/methods ; Humans ; Sequence Analysis, DNA/methods ; Software
    Language English
    Publishing date 2017-05-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btw835
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity.

    Giroux, Nicholas S / Ding, Shengli / McClain, Micah T / Burke, Thomas W / Petzold, Elizabeth / Chung, Hong A / Palomino, Grecia R / Wang, Ergang / Xi, Rui / Bose, Shree / Rotstein, Tomer / Nicholson, Bradly P / Chen, Tianyi / Henao, Ricardo / Sempowski, Gregory D / Denny, Thomas N / Ko, Emily R / Ginsburg, Geoffrey S / Kraft, Bryan D /
    Tsalik, Ephraim L / Woods, Christopher W / Shen, Xiling

    bioRxiv : the preprint server for biology

    2020  

    Abstract: SARS-CoV-2 infection triggers highly variable host responses and causes varying degrees of illness in humans. We sought to harness the peripheral blood mononuclear cell (PBMC) response over the course of illness to provide insight into COVID-19 ... ...

    Abstract SARS-CoV-2 infection triggers highly variable host responses and causes varying degrees of illness in humans. We sought to harness the peripheral blood mononuclear cell (PBMC) response over the course of illness to provide insight into COVID-19 physiology. We analyzed PBMCs from subjects with variable symptom severity at different stages of clinical illness before and after IgG seroconversion to SARS-CoV-2. Prior to seroconversion, PBMC transcriptomes did not distinguish symptom severity. In contrast, changes in chromatin accessibility were associated with symptom severity. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif occupancy for individual PBMC cell types. The most extensive remodeling occurred in CD14+ monocytes where sub-populations with distinct chromatin accessibility profiles were associated with disease severity. Our findings indicate that pre-seroconversion chromatin remodeling in certain innate immune populations is associated with divergence in symptom severity, and the identified transcription factors, regulatory elements, and downstream pathways provide potential prognostic markers for COVID-19 subjects.
    Language English
    Publishing date 2020-12-09
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2020.12.04.412155
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity

    Giroux, Nicholas S. / Ding, Shengli / McClain, Micah T. / Burke, Thomas W. / Petzold, Elizabeth W. / Chung, Hong A. / Palomino, Grecia R. / Wang, Ergang / Xi, Rui / Bose, Shree / Rotstein, Tomer / Nicholson, Bradly P. / Chen, Tianyi / Henao, Ricardo / Sempowski, Gregory D. / Denny, Thomas N. / Ko, Emily R. / Ginsburg, Geoffrey S. / Kraft, Bryan D. /
    Tsalik, Ephraim L. / Woods, Christopher W. / Shen, Xiling

    bioRxiv

    Abstract: SARS-CoV-2 infection triggers highly variable host responses and causes varying degrees of illness in humans. We sought to harness the peripheral blood mononuclear cell (PBMC) response over the course of illness to provide insight into COVID-19 ... ...

    Abstract SARS-CoV-2 infection triggers highly variable host responses and causes varying degrees of illness in humans. We sought to harness the peripheral blood mononuclear cell (PBMC) response over the course of illness to provide insight into COVID-19 physiology. We analyzed PBMCs from subjects with variable symptom severity at different stages of clinical illness before and after IgG seroconversion to SARS-CoV-2. Prior to seroconversion, PBMC transcriptomes did not distinguish symptom severity. In contrast, changes in chromatin accessibility were associated with symptom severity. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif occupancy for individual PBMC cell types. The most extensive remodeling occurred in CD14+ monocytes where sub-populations with distinct chromatin accessibility profiles were associated with disease severity. Our findings indicate that pre-seroconversion chromatin remodeling in certain innate immune populations is associated with divergence in symptom severity, and the identified transcription factors, regulatory elements, and downstream pathways provide potential prognostic markers for COVID-19 subjects.
    Keywords covid19
    Language English
    Publishing date 2020-12-05
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.12.04.412155
    Database COVID19

    Kategorien

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