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  1. AU="Pardis C. Sabeti"
  2. AU=Arkowitz Robert A
  3. AU="Sempoux, Christine"
  4. AU="Selebatso, Moses"
  5. AU=Sountoulides Petros
  6. AU="Huachun Zou"
  7. AU=SHENG Nan AU=SHENG Nan
  8. AU="Gascon, Pierre"
  9. AU="Hoa Phong, Pham Huu Thien"
  10. AU="Guiyan Ni"

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  1. Artikel ; Online: Containing the spread of mumps on college campuses

    Mirai Shah / Gabrielle Ferra / Susan Fitzgerald / Paul J. Barreira / Pardis C. Sabeti / Andrés Colubri

    Royal Society Open Science, Vol 9, Iss

    2022  Band 1

    Abstract: College campuses are vulnerable to infectious disease outbreaks, and there is an urgent need to develop better strategies to mitigate their size and duration, particularly as educational institutions around the world adapt to in-person instruction during ...

    Abstract College campuses are vulnerable to infectious disease outbreaks, and there is an urgent need to develop better strategies to mitigate their size and duration, particularly as educational institutions around the world adapt to in-person instruction during the COVID-19 pandemic. Towards addressing this need, we applied a stochastic compartmental model to quantify the impact of university-level responses to contain a mumps outbreak at Harvard University in 2016. We used our model to determine which containment interventions were most effective and study alternative scenarios without and with earlier interventions. This model allows for stochastic variation in small populations, missing or unobserved case data and changes in disease transmission rates post-intervention. The results suggest that control measures implemented by the University's Health Services, including rapid isolation of suspected cases, were very effective at containing the outbreak. Without those measures, the outbreak could have been four times larger. More generally, we conclude that universities should apply (i) diagnostic protocols that address false negatives from molecular tests and (ii) strict quarantine policies to contain the spread of easily transmissible infectious diseases such as mumps among their students. This modelling approach could be applied to data from other outbreaks in college campuses and similar small population settings.
    Schlagwörter infectious disease ; mumps outbreak ; college campus ; stochastic susceptible exposed infectious recovered model ; public health intervention ; Harvard University ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2022-01-01T00:00:00Z
    Verlag The Royal Society
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: The HLA-II immunopeptidome of SARS-CoV-2

    Shira Weingarten-Gabbay / Da-Yuan Chen / Siranush Sarkizova / Hannah B. Taylor / Matteo Gentili / Gabrielle M. Hernandez / Leah R. Pearlman / Matthew R. Bauer / Charles M. Rice / Karl R. Clauser / Nir Hacohen / Steven A. Carr / Jennifer G. Abelin / Mohsan Saeed / Pardis C. Sabeti

    Cell Reports, Vol 43, Iss 1, Pp 113596- (2024)

    1481  

    Abstract: Summary: Targeted synthetic vaccines have the potential to transform our response to viral outbreaks, yet the design of these vaccines requires a comprehensive knowledge of viral immunogens. Here, we report severe acute respiratory syndrome coronavirus 2 ...

    Abstract Summary: Targeted synthetic vaccines have the potential to transform our response to viral outbreaks, yet the design of these vaccines requires a comprehensive knowledge of viral immunogens. Here, we report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides that are naturally processed and loaded onto human leukocyte antigen-II (HLA-II) complexes in infected cells. We identify over 500 unique viral peptides from canonical proteins as well as from overlapping internal open reading frames. Most HLA-II peptides colocalize with known CD4+ T cell epitopes in coronavirus disease 2019 patients, including 2 reported immunodominant regions in the SARS-CoV-2 membrane protein. Overall, our analyses show that HLA-I and HLA-II pathways target distinct viral proteins, with the structural proteins accounting for most of the HLA-II peptidome and nonstructural and noncanonical proteins accounting for the majority of the HLA-I peptidome. These findings highlight the need for a vaccine design that incorporates multiple viral elements harboring CD4+ and CD8+ T cell epitopes to maximize vaccine effectiveness.
    Schlagwörter CP: Microbiology ; CP: Immunology ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2024-01-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Antigen test swabs are comparable to nasopharyngeal swabs for sequencing of SARS-CoV-2

    Sayf Al-Deen Hassouneh / Alexa Trujillo / Sobur Ali / Eleonora Cella / Catherine Johnston / Katherine C. DeRuff / Pardis C. Sabeti / Taj Azarian

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Band 7

    Abstract: Abstract Viral genomic surveillance has been integral in the global response to the SARS-CoV-2 pandemic. Surveillance efforts rely on the availability of representative clinical specimens from ongoing testing activities. However, testing practices have ... ...

    Abstract Abstract Viral genomic surveillance has been integral in the global response to the SARS-CoV-2 pandemic. Surveillance efforts rely on the availability of representative clinical specimens from ongoing testing activities. However, testing practices have recently shifted due to the widespread availability and use of rapid antigen tests, which could lead to gaps in future monitoring efforts. As such, genomic surveillance strategies must adapt to include laboratory workflows that are robust to sample type. To that end, we compare the results of RT-qPCR and viral genome sequencing using samples from positive BinaxNOW COVID-19 Antigen Card swabs (N = 555) to those obtained from nasopharyngeal (NP) swabs used for nucleic acid amplification testing (N = 135). We show that swabs obtained from antigen cards are comparable in performance to samples from NP swabs, providing a viable alternative and allowing for the potential expansion of viral genomic surveillance to outpatient clinic as well as other settings where rapid antigen tests are often used.
    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2023-07-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; 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  Band 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.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2023-02-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Single-cell profiling of lncRNA expression during Ebola virus infection in rhesus macaques

    Luisa Santus / Maria Sopena-Rios / Raquel García-Pérez / Aaron E. Lin / Gordon C. Adams / Kayla G. Barnes / Katherine J. Siddle / Shirlee Wohl / Ferran Reverter / John L. Rinn / Richard S. Bennett / Lisa E. Hensley / Pardis C. Sabeti / Marta Melé

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

    2023  Band 14

    Abstract: Abstract Long non-coding RNAs (lncRNAs) are involved in numerous biological processes and are pivotal mediators of the immune response, yet little is known about their properties at the single-cell level. Here, we generate a multi-tissue bulk RNAseq ... ...

    Abstract Abstract Long non-coding RNAs (lncRNAs) are involved in numerous biological processes and are pivotal mediators of the immune response, yet little is known about their properties at the single-cell level. Here, we generate a multi-tissue bulk RNAseq dataset from Ebola virus (EBOV) infected and not-infected rhesus macaques and identified 3979 novel lncRNAs. To profile lncRNA expression dynamics in immune circulating single-cells during EBOV infection, we design a metric, Upsilon, to estimate cell-type specificity. Our analysis reveals that lncRNAs are expressed in fewer cells than protein-coding genes, but they are not expressed at lower levels nor are they more cell-type specific when expressed in the same number of cells. In addition, we observe that lncRNAs exhibit similar changes in expression patterns to those of protein-coding genes during EBOV infection, and are often co-expressed with known immune regulators. A few lncRNAs change expression specifically upon EBOV entry in the cell. This study sheds light on the differential features of lncRNAs and protein-coding genes and paves the way for future single-cell lncRNA studies.
    Schlagwörter Science ; Q
    Thema/Rubrik (Code) 612
    Sprache Englisch
    Erscheinungsdatum 2023-06-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: HLA-I immunopeptidome profiling of human cells infected with high-containment enveloped viruses

    Shira Weingarten-Gabbay / Leah R. Pearlman / Da-Yuan Chen / Susan Klaeger / Hannah B. Taylor / Nicole L. Welch / Derin B. Keskin / Steven A. Carr / Jennifer G. Abelin / Mohsan Saeed / Pardis C. Sabeti

    STAR Protocols, Vol 3, Iss 4, Pp 101910- (2022)

    2022  

    Abstract: Summary: Immunopeptidome profiling of infected cells is a powerful technique for detecting viral peptides that are naturally processed and loaded onto class I human leukocyte antigens (HLAs-I). Here, we provide a protocol for preparing samples for ... ...

    Abstract Summary: Immunopeptidome profiling of infected cells is a powerful technique for detecting viral peptides that are naturally processed and loaded onto class I human leukocyte antigens (HLAs-I). Here, we provide a protocol for preparing samples for immunopeptidome profiling that can inactivate enveloped viruses while still preserving the integrity of the HLA-I complex. We detail steps for lysate preparation of infected cells followed by HLA-I immunoprecipitation and virus inactivation. We further describe peptide purification for mass spectrometry outside a high-containment facility.For complete details on the use and execution of this protocol, please refer to Weingarten-Gabbay et al. (2021).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
    Schlagwörter Immunology ; Microbiology ; Mass Spectrometry ; Science (General) ; Q1-390
    Sprache Englisch
    Erscheinungsdatum 2022-12-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: The case for altruism in institutional diagnostic testing

    Ivan Specht / Kian Sani / Yolanda Botti-Lodovico / Michael Hughes / Kristin Heumann / Amy Bronson / John Marshall / Emily Baron / Eric Parrie / Olivia Glennon / Ben Fry / Andrés Colubri / Pardis C. Sabeti

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Band 7

    Abstract: Abstract Amid COVID-19, many institutions deployed vast resources to test their members regularly for safe reopening. This self-focused approach, however, not only overlooks surrounding communities but also remains blind to community transmission that ... ...

    Abstract Abstract Amid COVID-19, many institutions deployed vast resources to test their members regularly for safe reopening. This self-focused approach, however, not only overlooks surrounding communities but also remains blind to community transmission that could breach the institution. To test the relative merits of a more altruistic strategy, we built an epidemiological model that assesses the differential impact on case counts when institutions instead allocate a proportion of their tests to members’ close contacts in the larger community. We found that testing outside the institution benefits the institution in all plausible circumstances, with the optimal proportion of tests to use externally landing at 45% under baseline model parameters. Our results were robust to local prevalence, secondary attack rate, testing capacity, and contact reporting level, yielding a range of optimal community testing proportions from 18 to 58%. The model performed best under the assumption that community contacts are known to the institution; however, it still demonstrated a significant benefit even without complete knowledge of the contact network.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 306
    Sprache Englisch
    Erscheinungsdatum 2022-02-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Identifying gene expression programs of cell-type identity and cellular activity with single-cell RNA-Seq

    Dylan Kotliar / Adrian Veres / M Aurel Nagy / Shervin Tabrizi / Eran Hodis / Douglas A Melton / Pardis C Sabeti

    eLife, Vol

    2019  Band 8

    Abstract: Identifying gene expression programs underlying both cell-type identity and cellular activities (e.g. life-cycle processes, responses to environmental cues) is crucial for understanding the organization of cells and tissues. Although single-cell RNA-Seq ( ...

    Abstract Identifying gene expression programs underlying both cell-type identity and cellular activities (e.g. life-cycle processes, responses to environmental cues) is crucial for understanding the organization of cells and tissues. Although single-cell RNA-Seq (scRNA-Seq) can quantify transcripts in individual cells, each cell’s expression profile may be a mixture of both types of programs, making them difficult to disentangle. Here, we benchmark and enhance the use of matrix factorization to solve this problem. We show with simulations that a method we call consensus non-negative matrix factorization (cNMF) accurately infers identity and activity programs, including their relative contributions in each cell. To illustrate the insights this approach enables, we apply it to published brain organoid and visual cortex scRNA-Seq datasets; cNMF refines cell types and identifies both expected (e.g. cell cycle and hypoxia) and novel activity programs, including programs that may underlie a neurosecretory phenotype and synaptogenesis.
    Schlagwörter gene expression programs ; single-cell Rna-Seq ; matrix factorization ; visual cortex ; brain organoids ; synaptogenesis ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 612
    Sprache Englisch
    Erscheinungsdatum 2019-07-01T00:00:00Z
    Verlag eLife Sciences Publications Ltd
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: Development of a SNP barcode to genotype Babesia microti infections.

    Mary Lynn Baniecki / Jade Moon / Kian Sani / Jacob E Lemieux / Stephen F Schaffner / Pardis C Sabeti

    PLoS Neglected Tropical Diseases, Vol 13, Iss 3, p e

    2019  Band 0007194

    Abstract: Babesia microti is tick-borne disease that is an emerging threat to public health due to increasing prevalence and expanding geographic range. Detection and constant surveillance of babesiosis is imperative for predicting pathogen expansion. Leveraging ... ...

    Abstract Babesia microti is tick-borne disease that is an emerging threat to public health due to increasing prevalence and expanding geographic range. Detection and constant surveillance of babesiosis is imperative for predicting pathogen expansion. Leveraging our whole genome sequence (WGS) analyses of B. microti, we developed a single nucleotide polymorphism (SNP)-based high resolution melt (HRM) surveillance tool. We developed our HRM assay using available sequence data and identified 775 SNPs. From these candidate SNPs, we developed a 32-SNP barcode that is robust and differentiates geographically distinct populations; it contains SNPs that are putatively neutral, located in nuclear, mitochondrial, and apicoplastal regions. The assays are reproducible and robust, requiring a small quantity of DNA (limit of detection as low as 10 pg.). We analyzed the performance of our HRM assay using 26 B. microti clinical samples used in our WGS study from babesiosis endemic regions in the United States. We identified a minimal barcode consisting of 25 SNPs that differentiate geographically distinct populations across all clinical samples evaluated (average minor allele frequency > 0.22). Supporting our previous WGS findings, our 25-SNP barcode identified distinct barcode signatures that segregate B. microti into two lineages: Northeast and Midwest, with the Northeast having three subpopulations: Connecticut/Rhode Island, Nantucket, and the R1 reference group. Our 25-SNP HRM barcode provides a robust means genetic marker set that will aid in tracking the increasing incidence and expanding geographic range of B. microti infections.
    Schlagwörter Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Sprache Englisch
    Erscheinungsdatum 2019-03-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: Machine-learning Prognostic Models from the 2014–16 Ebola Outbreak

    Andres Colubri / Mary-Anne Hartley / Matthew Siakor / Vanessa Wolfman / August Felix / Tom Sesay / Jeffrey G. Shaffer / Robert F. Garry / Donald S. Grant / Adam C. Levine / Pardis C. Sabeti

    EClinicalMedicine, Vol 11, Iss , Pp 54-

    Data-harmonization Challenges, Validation Strategies, and mHealth Applications

    2019  Band 64

    Abstract: Background: Ebola virus disease (EVD) plagues low-resource and difficult-to-access settings. Machine learning prognostic models and mHealth tools could improve the understanding and use of evidence-based care guidelines in such settings. However, data ... ...

    Abstract Background: Ebola virus disease (EVD) plagues low-resource and difficult-to-access settings. Machine learning prognostic models and mHealth tools could improve the understanding and use of evidence-based care guidelines in such settings. However, data incompleteness and lack of interoperability limit model generalizability. This study harmonizes diverse datasets from the 2014–16 EVD epidemic and generates several prognostic models incorporated into the novel Ebola Care Guidelines app that provides informed access to recommended evidence-based guidelines. Methods: Multivariate logistic regression was applied to investigate survival outcomes in 470 patients admitted to five Ebola treatment units in Liberia and Sierra Leone at various timepoints during 2014–16. We generated a parsimonious model (viral load, age, temperature, bleeding, jaundice, dyspnea, dysphagia, and time-to-presentation) and several fallback models for when these variables are unavailable. All were externally validated against two independent datasets and compared to further models including expert observational wellness assessments. Models were incorporated into an app highlighting the signs/symptoms with the largest contribution to prognosis. Findings: The parsimonious model approached the predictive power of observational assessments by experienced clinicians (Area-Under-the-Curve, AUC = 0.70–0.79, accuracy = 0.64–0.74) and maintained its performance across subcohorts with different healthcare seeking behaviors. Age and viral load contributed >5-fold the weighting of other features and including them in a minimal model had a similar AUC, albeit at the cost of specificity. Interpretation: Clinically guided prognostic models can recapitulate clinical expertise and be useful when such expertise is unavailable. Incorporating these models into mHealth tools may facilitate their interpretation and provide informed access to comprehensive clinical guidelines. Funding: Howard Hughes Medical Institute, US National Institutes of Health, Bill & ...
    Schlagwörter Medicine (General) ; R5-920
    Thema/Rubrik (Code) 310
    Sprache Englisch
    Erscheinungsdatum 2019-05-01T00:00:00Z
    Verlag Elsevier
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    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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