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1. Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality

Author

Gygi, Jeremy P, Maguire, Cole, Patel, Ravi K, Shinde, Pramod, Konstorum, Anna, Shannon, Casey P, Xu, Leqi, Hoch, Annmarie, Jayavelu, Naresh Doni, Haddad, Elias K, Network, IMPACC, Reed, Elaine F, Kraft, Monica, McComsey, Grace A, Metcalf, Jordan P, Ozonoff, Al, Esserman, Denise, Cairns, Charles B, Rouphael, Nadine, Bosinger, Steven E, Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey B, van Bakel, Harm, Wilson, Michael, Eckalbar, Walter L, Maecker, Holden T, Langelier, Charles R, Steen, Hanno, Altman, Matthew C, Montgomery, Ruth R, Levy, Ofer, Melamed, Esther, Pulendran, Bali, Diray-Arce, Joann, Smolen, Kinga K, Fragiadakis, Gabriela K, Becker, Patrice M, Sekaly, Rafick P, Ehrlich, Lauren IR, Fourati, Slim, Peters, Bjoern, Kleinstein, Steven H, and Guan, Leying

Subjects
Biomedical and Clinical Sciences, Immunology, Clinical Research, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Humans, COVID-19, Male, Longitudinal Studies, SARS-CoV-2, Female, Middle Aged, Severity of Illness Index, Aged, Adult, Cytokines, Multiomics, IMPACC Network, Adaptive immunity, Innate immunity, Medical and Health Sciences, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.RESULTSIncreasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, formation of neutrophil extracellular traps, and T cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma Igs and B cells and dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to failure of viral clearance in patients with fatal illness.CONCLUSIONOur longitudinal multiomics profiling study revealed temporal coordination across diverse omics that potentially explain the disease progression, providing insights that can inform the targeted development of therapies for patients hospitalized with COVID-19, especially those who are critically ill.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, and R01AI122220); and National Science Foundation (DMS2310836).

Published
2024

2. IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition

Author

Ozonoff, Al, Ehrlich, Lauren IR, Melamed, Esther, Sesma, Ana Fernandez, Simon, Viviana, Pulendran, Bali, Nadeau, Kari C, Davis, Mark M, McCoey, Grace A, Sekaly, Rafick, Baden, Lindsey R, Levy, Ofer, Schaenman, Joanna, Reed, Elaine F, Shaw, Albert C, Hafler, David A, Montgomery, Ruth R, Kleinstein, Steven H, Becker, Patrice M, Augustine, Alison D, Calfee, Carolyn S, Erle, David J, DeBakey, Michael E, Corry, David B, Kheradmand, Farrah, Atkinson, Mark A, Brakenridge, Scott C, Higuita, Nelson I Agudelo, Metcalf, Jordan P, Hough, Catherine L, Messer, William B, Kraft, Monica, Bime, Chris, Peters, Bjoern, Milliren, Carly E, Syphurs, Caitlin, McEnaney, Kerry, Barton, Brenda, Lentucci, Claudia, Saluvan, Mehmet, Chang, Ana C, Hoch, Annmarie, Albert, Marisa, Shaheen, Tanzia, Kho, Alvin T, Liu, Shanshan, Thomas, Sanya, Chen, Jing, Murphy, Maimouna D, Cooney, Mitchell, Hayati, Arash Nemati, Bryant, Robert, Abraham, James, Jayavelu, Naresh Doni, Presnell, Scott, Jancsyk, Tomasz, Maguire, Cole, Qi, Jingjing, Lee, Brian, Fourati, Slim, Esserman, Denise A, Guan, Leying, Gygi, Jeremy, Pawar, Shrikant, Brito, Anderson, Fragiadakis, Gabriela K, Patel, Ravi, Overton, James A, Vita, Randi, Westendorf, Kerstin, Shannon, Casey P, Tebbutt, Scott J, Thyagarajan, Rama V, Rousseau, Justin F, Wylie, Dennis, Triplett, Todd A, Kojic, Erna, Chinthrajah, Sharon, Ahuja, Neera, Rogers, Angela J, Artandi, Maja, Geng, Linda, Yendewa, George, Powell, Debra L, Kim, James N, Simmons, Brent, Goonewardene, I Michael, Smith, Cecilia M, Martens, Mark, Sherman, Amy C, Walsh, Stephen R, Issa, Nicolas C, Salehi-Rad, Ramin, Dela Cruz, Charles, Farhadian, Shelli, Iwasaki, Akiko, Ko, Albert I, Anderson, Evan J, Mehta, Aneesh K, and Sevransky, Jonathan E

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Coronaviruses, Lung, Emerging Infectious Diseases, Inflammatory and immune system, Good Health and Well Being, Humans, COVID-19, Glycosylation, SARS-CoV-2, Glycosyltransferases, Complement System Proteins, Immunoglobulin M, IMPACC Network
Abstract

The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.

Published
2024

3. Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study

Author

Ozonoff, Al, Jayavelu, Naresh Doni, Liu, Shanshan, Melamed, Esther, Milliren, Carly E., Qi, Jingjing, Geng, Linda N., McComsey, Grace A., Cairns, Charles B., Baden, Lindsey R., Schaenman, Joanna, Shaw, Albert C., Samaha, Hady, Seyfert-Margolis, Vicki, Krammer, Florian, Rosen, Lindsey B., Steen, Hanno, Syphurs, Caitlin, Dandekar, Ravi, Shannon, Casey P., Sekaly, Rafick P., Ehrlich, Lauren I. R., Corry, David B., Kheradmand, Farrah, Atkinson, Mark A., Brakenridge, Scott C., Higuita, Nelson I. Agudelo, Metcalf, Jordan P., Hough, Catherine L., Messer, William B., Pulendran, Bali, Nadeau, Kari C., Davis, Mark M., Sesma, Ana Fernandez, Simon, Viviana, van Bakel, Harm, Kim-Schulze, Seunghee, Hafler, David A., Levy, Ofer, Kraft, Monica, Bime, Chris, Haddad, Elias K., Calfee, Carolyn S., Erle, David J., Langelier, Charles R., Eckalbar, Walter, Bosinger, Steven E., Peters, Bjoern, Kleinstein, Steven H., Reed, Elaine F., Augustine, Alison D., Diray-Arce, Joann, Maecker, Holden T., Altman, Matthew C., Montgomery, Ruth R., Becker, Patrice M., and Rouphael, Nadine

Published
2024
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5. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study

Author

Ozonoff, Al, Schaenman, Joanna, Jayavelu, Naresh Doni, Milliren, Carly E, Calfee, Carolyn S, Cairns, Charles B, Kraft, Monica, Baden, Lindsey R, Shaw, Albert C, Krammer, Florian, van Bakel, Harm, Esserman, Denise A, Liu, Shanshan, Sesma, Ana Fernandez, Simon, Viviana, Hafler, David A, Montgomery, Ruth R, Kleinstein, Steven H, Levy, Ofer, Bime, Christian, Haddad, Elias K, Erle, David J, Pulendran, Bali, Nadeau, Kari C, Davis, Mark M, Hough, Catherine L, Messer, William B, Higuita, Nelson I Agudelo, Metcalf, Jordan P, Atkinson, Mark A, Brakenridge, Scott C, Corry, David, Kheradmand, Farrah, Ehrlich, Lauren IR, Melamed, Esther, McComsey, Grace A, Sekaly, Rafick, Diray-Arce, Joann, Peters, Bjoern, Augustine, Alison D, Reed, Elaine F, Altman, Matthew C, Becker, Patrice M, Rouphael, Nadine, Bime, Chris, McEnaney, Kerry, Barton, Brenda, Lentucci, Claudia, Saluvan, Mehmet, Chang, Ana C, Hoch, Annmarie, Albert, Marisa, Shaheen, Tanzia, Kho, Alvin T, Thomas, Sanya, Chen, Jing, Murphy, Maimouna D, Cooney, Mitchell, Presnell, Scott, and Fragiadakis, Gabriela K

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Emerging Infectious Diseases, Lung, Genetics, Clinical Research, Coronaviruses, Prevention, Good Health and Well Being, COVID-19, Creatinine, Female, Hospitalization, Humans, Male, Phenotype, Prospective Studies, RNA, Viral, SARS-CoV-2, Severity of Illness Index, Troponin, Post-Acute COVID-19 Syndrome, Viral load, Antibody, IMPACC study group members, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundBetter understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.MethodsImmunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed.FindingsThe median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC.InterpretationIntegration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19.FundingNIH.

Published
2022

6. Activated sputum eosinophils associated with exacerbations in children on mepolizumab

Author

Wilson, Gabriella E., Knight, James, Liu, Qing, Shelar, Ashish, Stewart, Emma, Wang, Xiaomei, Yan, Xiting, Sanders, Joshua, Visness, Cynthia, Gill, Michelle, Gruchalla, Rebecca, Liu, Andrew H., Kattan, Meyer, Khurana Hershey, Gurjit K., Togias, Alkis, Becker, Patrice M., Altman, Matthew C., Busse, William W., Jackson, Daniel J., Montgomery, Ruth R., and Chupp, Geoffrey L.

Published
2024
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7. “Deficiency in ELF4, X-Linked”: a Monogenic Disease Entity Resembling Behçet’s Syndrome and Inflammatory Bowel Disease

Author

Olyha, Sam J., O’Connor, Shannon K., Kribis, Marat, Bucklin, Molly L., Uthaya Kumar, Dinesh Babu, Tyler, Paul M., Alam, Faiad, Jones, Kate M., Sheikha, Hassan, Konnikova, Liza, Lakhani, Saquib A., Montgomery, Ruth R., Catanzaro, Jason, Du, Hongqiang, DiGiacomo, Daniel V., Rothermel, Holly, Moran, Christopher J., Fiedler, Karoline, Warner, Neil, Hoppenreijs, Esther P.A.H., van der Made, Caspar I., Hoischen, Alexander, Olbrich, Peter, Neth, Olaf, Rodríguez-Martínez, Alejandro, Lucena Soto, José Manuel, van Rossum, Annemarie M.C., Dalm, Virgil A.S.H., Muise, Aleixo M., and Lucas, Carrie L.

Published
2024
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8. Longitudinal serum proteomics analyses identify unique and overlapping host response pathways in Lyme disease and West Nile virus infection

Author

Boada, Patrick, Fatou, Benoit, Belperron, Alexia A, Sigdel, Tara K, Smolen, Kinga K, Wurie, Zainab, Levy, Ofer, Ronca, Shannon E, Murray, Kristy O, Liberto, Juliane M, Rashmi, Priyanka, Kerwin, Maggie, Montgomery, Ruth R, Bockenstedt, Linda K, Steen, Hanno, and Sarwal, Minnie M

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Biotechnology, Vector-Borne Diseases, Emerging Infectious Diseases, Biodefense, West Nile Virus, Rare Diseases, Infectious Diseases, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, Humans, West Nile Fever, West Nile virus, Proteome, Proteomics, Lyme Disease, serum proteomics, acute-phase response, immune system, localized and disseminated stage, asymptomatic infection, Lyme disease, longitudinal analysis, Immunology, Biochemistry and cell biology, Genetics
Abstract

Advancement in proteomics methods for interrogating biological samples has helped identify disease biomarkers for early diagnostics and unravel underlying molecular mechanisms of disease. Herein, we examined the serum proteomes of 23 study participants presenting with one of two common arthropod-borne infections: Lyme disease (LD), an extracellular bacterial infection or West Nile virus infection (WNV), an intracellular viral infection. The LC/MS based serum proteomes of samples collected at the time of diagnosis and during convalescence were assessed using a depletion-based high-throughput shotgun proteomics (dHSP) pipeline as well as a non-depleting blotting-based low-throughput platform (MStern). The LC/MS integrated analyses identified host proteome responses in the acute and recovery phases shared by LD and WNV infections, as well as differentially abundant proteins that were unique to each infection. Notably, we also detected proteins that distinguished localized from disseminated LD and asymptomatic from symptomatic WNV infection. The proteins detected in both diseases with the dHSP pipeline identified unique and overlapping proteins detected with the non-depleting MStern platform, supporting the utility of both detection methods. Machine learning confirmed the use of the serum proteome to distinguish the infection from healthy control sera but could not develop discriminatory models between LD and WNV at current sample numbers. Our study is the first to compare the serum proteomes in two arthropod-borne infections and highlights the similarities in host responses even though the pathogens and the vectors themselves are different.

Published
2022

9. Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study

Author

Rouphael, Nadine, Maecker, Holden, Montgomery, Ruth R, Diray-Arce, Joann, Kleinstein, Steven H, Altman, Matthew C, Bosinger, Steven E, Eckalbar, Walter, Guan, Leying, Hough, Catherine L, Krammer, Florian, Langelier, Charles, Levy, Ofer, McEnaney, Kerry, Peters, Bjoern, Rahman, Adeeb, Rajan, Jayant V, Sigelman, Steven, Steen, Hanno, van Bakel, Harm, Ward, Alyssa, Wilson, Michael R, Woodruff, Prescott, Zamecnik, Colin R, Augustine, Alison D, Ozonoff, Al, Reed, Elaine F, Becker, Patrice M, Higuita, Nelson Agudelo, Atkinson, Mark A, Baden, Lindsey R, Bime, Christian, Brakenridge, Scott C, Calfee, Carolyn S, Cairns, Charles B, Corry, David, Davis, Mark M, Ehrlich, Lauren IR, Haddad, Elias K, Erle, David J, Fernandez-Sesma, Ana, Hafler, David A, Kheradmand, Farrah, Kraft, Monica, McComsey, Grace A, Melamed, Esther, Messer, William, Metcalf, Jordan, Nadeau, Kari C, Pulendran, Bali, Sarwal, Minnie, Schaenman, Joanna, Sekaly, Rafick, Shaw, Albert C, and Simon, Viviana

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Biomarkers, COVID-19, Computational Biology, Data Analysis, Gene Expression Profiling, Hospitalization, Humans, Immunophenotyping, Longitudinal Studies, Molecular Diagnostic Techniques, Prospective Studies, Proteomics, SARS-CoV-2, United States, IMPACC Manuscript Writing Team, IMPACC Network Steering Committee, Clinical sciences, Immunology
Abstract

The IMmunoPhenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective longitudinal study designed to enroll 1000 hospitalized patients with COVID-19 (NCT04378777). IMPACC collects detailed clinical, laboratory and radiographic data along with longitudinal biologic sampling of blood and respiratory secretions for in depth testing. Clinical and lab data are integrated to identify immunologic, virologic, proteomic, metabolomic and genomic features of COVID-19-related susceptibility, severity and disease progression. The goals of IMPACC are to better understand the contributions of pathogen dynamics and host immune responses to the severity and course of COVID-19 and to generate hypotheses for identification of biomarkers and effective therapeutics, including optimal timing of such interventions. In this report we summarize the IMPACC study design and protocols including clinical criteria and recruitment, multi-site standardized sample collection and processing, virologic and immunologic assays, harmonization of assay protocols, high-level analyses and the data sharing plans.

Published
2021

10. Early cellular and molecular signatures correlate with severity of West Nile virus infection

Author

Lee, Ho-Joon, Zhao, Yujiao, Fleming, Ira, Mehta, Sameet, Wang, Xiaomei, Wyk, Brent Vander, Ronca, Shannon E., Kang, Heather, Chou, Chih-Hung, Fatou, Benoit, Smolen, Kinga K., Levy, Ofer, Clish, Clary B., Xavier, Ramnik J., Steen, Hanno, Hafler, David A., Love, J. Christopher, Shalek, Alex K., Guan, Leying, Murray, Kristy O., Kleinstein, Steven H., and Montgomery, Ruth R.

Published
2023
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11. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

Author

Abraham, James, Adkisson, Michael, Albert, Marisa, Altamirano, Luz Torres, Alvarenga, Bonny, Anderson, Matthew L., Anderson, Evan J., Arnett, Azlann, Asashima, Hiromitsu, Atkinson, Mark A., Baden, Lindsey R., Barton, Brenda, Beach, Katherine, Beagle, Elizabeth, Becker, Patrice M., Bell, Matthew R., Bernui, Mariana, Bime, Christian, Boddapati, Arun Kumar, Booth, J. Leland, Borresen, Brittney, Brakenridge, Scott C., Bristow, Laurel, Bryant, Robert, Calfee, Carolyn S., Carreño, Juan Manuel, Carrillo, Sidney, Chak, Suzanna, Chang, Iris, Connors, Jennifer, Conway, Michelle, Corry, David B., Cowan, David, Croen, Brett, Dela Cruz, Charles S., Cusimano, Gina, Eaker, Lily, Edwards, Carolyn, Ehrlich, Lauren I.R., Elashoff, David, Erickson, Heidi, Erle, David J., Farhadian, Shelli, Farrugia, Keith, Fatou, Benoit, Fernandes, Andrea, Fernandez-Sesma, Ana, Fragiadakis, Gabriela K., Furukawa, Sara, Geltman, Janelle N., Ghale, Rajani, Bermúdez González, Maria Carolina, Goonewardene, I. Michael, Guerrero, Estella Sanchez, Guirgis, Faheem W., Hafler, David A., Hamilton, Sydney, Harris, Paul, Hayati, Arash Nemati, Hendrickson, Carolyn M., Agudelo Higuita, Nelson I., Hodder, Thomas, Holland, Steven M., Hough, Catherine L., Huerta, Christopher, Hurley, Kerin C., Hutton, Scott R., Iwasaki, Akiko, Jauregui, Alejandra, Jha, Meenakshi, Johnson, Brandi, Joyner, David, Kangelaris, Kirsten N., Kelly, Geoffrey, Khalil, Zain, Khan, Zenab, Kheradmand, Farrah, Kim, James N., Kimura, Hiroki, Ko, Albert I., Kohr, Bernard, Kraft, Monica, Krummel, Matthew, Kutzler, Michele A., Lasky-Su, Jessica, Lee, Serena, Lee, Deanna, Leipold, Michael, Lentucci, Claudia, Leroux, Carolyn, Lin, Edward, Liu, Shanshan, Love, Christina, Lu, Zhengchun, Maliskova, Lenka, Manning, Brittany Roth, Manohar, Monali, Martens, Mark, McComsey, Grace A., McEnaney, Kerry, McLin, Renee, Melamed, Esther, Melnyk, Nataliya, Mendez, Kevin, Messer, William B., Metcalf, Jordan P., Michelotti, Gregory, Mick, Eran, Mohanty, Subhasis, Mosier, Jarrod, Mulder, Lubbertus C.F., Murphy, Maimouna, Nadeau, Kari R.C., Nelson, Ebony, Nelson, Allison, Nguyen, Viet, Oberhaus, Jordan, Panganiban, Bernadine, Pellegrini, Kathryn L., Pickering, Harry C., Powell, Debra L., Presnell, Scott, Pulendran, Bali, Rahman, Adeeb H., Rashid, Ahmad Sadeed, Raskin, Ariel, Reed, Elaine F., Ribeiro, Susan Pereira, Rivera, Adreanne M., Rogers, Jacob E., Rogers, Angela, Rogowski, Brandon, Rooks, Rebecca, Rosenberg-Hasson, Yael, Rothman, Jessica, Rousseau, Justin F., Salehi-Rad, Ramin, Saluvan, Mehmet, Samaha, Hady, Schaenman, Joanna, Schunk, Ron, Semenza, Nicholas C., Sen, Subha, Sevransky, Jonathan, Seyfert-Margolis, Vicki, Shaheen, Tanzia, Shaw, Albert C., Sieg, Scott, Siegel, Sarah A.R., Sigal, Natalia, Siles, Nadia, Simmons, Brent, Simon, Viviana, Singh, Gagandeep, Sinko, Lauren, Smith, Cecilia M., Smolen, Kinga K., Song, Li-Zhen, Srivastava, Komal, Sullivan, Peter, Syphurs, Caitlin, Tcheou, Johnstone, Tegos, George P., Tharp, Greg K., Tong, Alexandra, Tsitsiklis, Alexandra, Ungaro, Ricardo F., Vaysman, Tatyana, Viode, Arthur, Vita, Randi, Wang, Xiaomei, Ward, Alyssa, Ward, Dawn C., Willmore, Andrew, Woloszczuk, Kyra, Wong, Kari, Woodruff, Prescott G., Xu, Leqi, van Haren, Simon, van de Guchte, Adriana, Zhao, Yujiao, Diray-Arce, Joann, Fourati, Slim, Doni Jayavelu, Naresh, Patel, Ravi, Maguire, Cole, Chang, Ana C., Dandekar, Ravi, Qi, Jingjing, Lee, Brian H., van Zalm, Patrick, Schroeder, Andrew, Chen, Ernie, Konstorum, Anna, Brito, Anderson, Gygi, Jeremy P., Kho, Alvin, Chen, Jing, Pawar, Shrikant, Gonzalez-Reiche, Ana Silvia, Hoch, Annmarie, Milliren, Carly E., Overton, James A., Westendorf, Kerstin, Cairns, Charles B., Rouphael, Nadine, Bosinger, Steven E., Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey, Grubaugh, Nathan D., van Bakel, Harm, Wilson, Michael, Rajan, Jayant, Steen, Hanno, Eckalbar, Walter, Cotsapas, Chris, Langelier, Charles R., Levy, Ofer, Altman, Matthew C., Maecker, Holden, Montgomery, Ruth R., Haddad, Elias K., Sekaly, Rafick P., Esserman, Denise, Ozonoff, Al, Augustine, Alison D., Guan, Leying, Peters, Bjoern, and Kleinstein, Steven H.

Published
2023
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13. A Modified Injector and Sample Acquisition Protocol Can Improve Data Quality and Reduce Inter‐Instrument Variability of the Helios Mass Cytometer

Author

Lee, Brian H, Kelly, Geoffrey, Bradford, Shermineh, Davila, Melanie, Guo, Xinzheng V, Amir, El‐Ad David, Thrash, Emily M, Solga, Michael D, Lannigan, Joanne, Sellers, Brian, Candia, Julian, Tsang, John, Montgomery, Ruth R, Tamaki, Stanley J, Sigdel, Tara K, Sarwal, Minnie M, Lanier, Lewis L, Tian, Yuan, Kim, Cheryl, Hinz, Denise, Peters, Bjoern, Sette, Alessandro, and Rahman, Adeeb H

Subjects
Analytical Chemistry, Chemical Sciences, Antibodies, Flow Cytometry, Humans, Immunophenotyping, Leukocytes, Mononuclear, Lymphocytes, Reproducibility of Results, Single-Cell Analysis, CyTOF, mass cytometry, immunology, Reproduciblity, variability, immune monitoring, Biochemistry and Cell Biology, Immunology, Cardiovascular medicine and haematology
Abstract

Mass cytometry is a powerful tool for high-dimensional single cell characterization. Since the introduction of the first commercial CyTOF mass cytometer by DVS Sciences in 2009, mass cytometry technology has matured and become more widely utilized, with sequential platform upgrades designed to address specific limitations and to expand the capabilities of the platform. Fluidigm's third-generation Helios mass cytometer introduced a number of upgrades over the previous CyTOF2. One of these new features is a modified narrow bore sample injector that generates smaller ion clouds, which is expected to improve sensitivity and throughput. However, following rigorous testing, we find that the narrow-bore sample injector may have unintended negative consequences on data quality and result in lower median and higher coefficients of variation in many antibody-associated signal intensities. We describe an alternative Helios acquisition protocol using a wider bore injector, which largely mitigates these data quality issues. We directly compare these two protocols in a multisite study of 10 Helios instruments across 7 institutions and show that the modified protocol improves data quality and reduces interinstrument variability. These findings highlight and address an important source of technical variability in mass cytometry experiments that is of particular relevance in the setting of multicenter studies. © 2019 International Society for Advancement of Cytometry.

Published
2019

14. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19

Author

Unterman, Avraham, Sumida, Tomokazu S., Nouri, Nima, Yan, Xiting, Zhao, Amy Y., Gasque, Victor, Schupp, Jonas C., Asashima, Hiromitsu, Liu, Yunqing, Cosme, Jr., Carlos, Deng, Wenxuan, Chen, Ming, Raredon, Micha Sam Brickman, Hoehn, Kenneth B., Wang, Guilin, Wang, Zuoheng, DeIuliis, Giuseppe, Ravindra, Neal G., Li, Ningshan, Castaldi, Christopher, Wong, Patrick, Fournier, John, Bermejo, Santos, Sharma, Lokesh, Casanovas-Massana, Arnau, Vogels, Chantal B. F., Wyllie, Anne L., Grubaugh, Nathan D., Melillo, Anthony, Meng, Hailong, Stein, Yan, Minasyan, Maksym, Mohanty, Subhasis, Ruff, William E., Cohen, Inessa, Raddassi, Khadir, Niklason, Laura E., Ko, Albert I., Montgomery, Ruth R., Farhadian, Shelli F., Iwasaki, Akiko, Shaw, Albert C., van Dijk, David, Zhao, Hongyu, Kleinstein, Steven H., Hafler, David A., Kaminski, Naftali, and Dela Cruz, Charles S.

Published
2022
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18. Corrigendum to “Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: results from the IMPACC study” [eBioMedicine 83 (2022) 104208]

Author

Ozonoff, Al, primary, Schaenman, Joanna, additional, Jayavelu, Naresh Doni, additional, Milliren, Carly E., additional, Calfee, Carolyn S., additional, Cairns, Charles B., additional, Kraft, Monica, additional, Baden, Lindsey R., additional, Shaw, Albert C., additional, Krammer, Florian, additional, van Bakel, Harm, additional, Esserman, Denise A., additional, Liu, Shanshan, additional, Sesma, Ana Fernandez, additional, Simon, Viviana, additional, Hafler, David A., additional, Montgomery, Ruth R., additional, Kleinstein, Steven H., additional, Levy, Ofer, additional, Bime, Chris, additional, Haddad, Elias K., additional, Erle, David J., additional, Pulendran, Bali, additional, Nadeau, Kari C., additional, Davis, Mark M., additional, Hough, Catherine L., additional, Messer, William B., additional, Agudelo Higuita, Nelson I., additional, Metcalf, Jordan P., additional, Atkinson, Mark A., additional, Brakenridge, Scott C., additional, Corry, David, additional, Kheradmand, Farrah, additional, Ehrlich, Lauren I.R., additional, Melamed, Esther, additional, McComsey, Grace A., additional, Sekaly, Rafick, additional, Diray-Arce, Joann, additional, Peters, Bjoern, additional, Augustine, Alison D., additional, Reed, Elaine F., additional, Altman, Matthew C., additional, Becker, Patrice M., additional, and Rouphael, Nadine, additional

Published
2023
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20. Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants

Author

Gygi, Jeremy P., primary, Maguire, Cole, additional, Patel, Ravi K., additional, Shinde, Pramod, additional, Konstorum, Anna, additional, Shannon, Casey P., additional, Xu, Leqi, additional, Hoch, Annmarie, additional, Jayavelu, Naresh Doni, additional, Network, IMPACC, additional, Haddad, Elias K., additional, Reed, Elaine F., additional, Kraft, Monica, additional, McComsey, Grace A., additional, Metcalf, Jordan, additional, Ozonoff, Al, additional, Esserman, Denise, additional, Cairns, Charles B., additional, Rouphael, Nadine, additional, Bosinger, Steven E., additional, Kim-Schulze, Seunghee, additional, Krammer, Florian, additional, Rosen, Lindsey B., additional, van Bakel, Harm, additional, Wilson, Michael, additional, Eckalbar, Walter, additional, Maecker, Holden, additional, Langelier, Charles R., additional, Steen, Hanno, additional, Altman, Matthew C., additional, Montgomery, Ruth R., additional, Levy, Ofer, additional, Melamed, Esther, additional, Pulendran, Bali, additional, Diray-Arce, Joann, additional, Smolen, Kinga K., additional, Fragiadakis, Gabriela K., additional, Becker, Patrice M., additional, Augustine, Alison D., additional, Sekaly, Rafick P., additional, Ehrlich, Lauren I. R., additional, Fourati, Slim, additional, Peters, Bjoern, additional, Kleinstein, Steven H., additional, and Guan, Leying, additional

Published
2023
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22. Proteome Analysis for Inflammation Related to Acute and Convalescent Infection

Author

Sigdel, Tara K., primary, Sur, Swastika, additional, Boada, Patrick, additional, McDermott, Suzanne M., additional, Arlehamn, Cecilia S. Lindestam, additional, Murray, Kristy O., additional, Bockenstedt, Linda K., additional, Kerwin, Maggie, additional, Reed, Elaine F., additional, Harris, Eva, additional, Stuart, Ken, additional, Peters, Bjoern, additional, Sesma, Ana, additional, Montgomery, Ruth R., additional, and Sarwal, Minnie M., additional

Published
2023
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24. Identification of genes critical for resistance to infection by West Nile virus using RNA-Seq analysis.

Author

Qian, Feng, Chung, Lisa, Zheng, Wei, Bruno, Vincent, Alexander, Roger P, Wang, Zhong, Wang, Xiaomei, Kurscheid, Sebastian, Zhao, Hongyu, Fikrig, Erol, Gerstein, Mark, Snyder, Michael, and Montgomery, Ruth R

Subjects
Macrophages, Humans, West Nile virus, RNA, Gene Expression Profiling, Adult, Female, Male, Gene Knockdown Techniques, Young Adult, High-Throughput Nucleotide Sequencing, Disease Resistance, anti-viral gene expression, immune response, macrophage, RNA-Seq, Microbiology
Abstract

The West Nile virus (WNV) is an emerging infection of biodefense concern and there are no available treatments or vaccines. Here we used a high-throughput method based on a novel gene expression analysis, RNA-Seq, to give a global picture of differential gene expression by primary human macrophages of 10 healthy donors infected in vitro with WNV. From a total of 28 million reads per sample, we identified 1,514 transcripts that were differentially expressed after infection. Both predicted and novel gene changes were detected, as were gene isoforms, and while many of the genes were expressed by all donors, some were unique. Knock-down of genes not previously known to be associated with WNV resistance identified their critical role in control of viral infection. Our study distinguishes both common gene pathways as well as novel cellular responses. Such analyses will be valuable for translational studies of susceptible and resistant individuals--and for targeting therapeutics--in multiple biological settings.

Published
2013

29. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination

Author

Asashima, Hiromitsu, primary, Kim, Dongjoo, additional, Wang, Kaicheng, additional, Lele, Nikhil, additional, Buitrago-Pocasangre, Nicholas C., additional, Lutz, Rachel, additional, Cruz, Isabella, additional, Raddassi, Khadir, additional, Ruff, William E., additional, Racke, Michael K., additional, Wilson, JoDell E., additional, Givens, Tara S., additional, Grifoni, Alba, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Kleinstein, Steven H., additional, Montgomery, Ruth R., additional, Shaw, Albert C., additional, Li, Fangyong, additional, Fan, Rong, additional, Hafler, David A., additional, Tomayko, Mary M., additional, and Longbrake, Erin E., additional

Published
2023
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30. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

Author

Diray-Arce, Joann, Fourati, Slim, Doni Jayavelu, Naresh, Patel, Ravi, Maguire, Cole, Chang, Ana C, Dandekar, Ravi, Qi, Jingjing, Lee, Brian H, van Zalm, Patrick, Schroeder, Andrew, Chen, Ernie, Konstorum, Anna, Brito, Anderson, Gygi, Jeremy P, Kho, Alvin, Chen, Jing, Pawar, Shrikant, Gonzalez-Reiche, Ana Silvia, Hoch, Annmarie, Milliren, Carly E, Overton, James A, Westendorf, Kerstin, IMPACC Network, Cairns, Charles B, Rouphael, Nadine, Bosinger, Steven E, Kim-Schulze, Seunghee, Krammer, Florian, Rosen, Lindsey, Grubaugh, Nathan D, van Bakel, Harm, Wilson, Michael, Rajan, Jayant, Steen, Hanno, Eckalbar, Walter, Cotsapas, Chris, Langelier, Charles R, Levy, Ofer, Altman, Matthew C, Maecker, Holden, Montgomery, Ruth R, Haddad, Elias K, Sekaly, Rafick P, Esserman, Denise, Ozonoff, Al, Becker, Patrice M, Augustine, Alison D, Guan, Leying, Peters, Bjoern, and Kleinstein, Steven H

Subjects
screening and diagnosis, IMPACC Network, SARS-CoV-2, longitudinal modeling, Prevention, COVID-19, systems immunology, multi-omics, Multiomics, 4.1 Discovery and preclinical testing of markers and technologies, Detection, Rare Diseases, Good Health and Well Being, immunophenotyping, Clinical Research, Disease Progression, Humans, 2.1 Biological and endogenous factors, Longitudinal Studies, Aetiology
Abstract

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.

Published
2023

31. Early cellular and molecular signatures correlate with severity of West Nile Virus infection

Author

Lee, Ho-Joon, primary, Zhao, Yujiao, additional, Fleming, Ira, additional, Mehta, Sameet, additional, Wang, Xiaomei, additional, Wyk, Brent Vander, additional, Ronca, Shannon E., additional, Kang, Heather, additional, Chou, Chih-Hung, additional, Fatou, Benoit, additional, Smolen, Kinga K., additional, Levy, Ofer, additional, Clish, Clary B., additional, Xavier, Ramnik J., additional, Steen, Hanno, additional, Hafler, David A., additional, Love, J. Christopher, additional, Shalek, Alex K., additional, Guan, Leying, additional, Murray, Kristy O., additional, Kleinstein, Steven H., additional, and Montgomery, Ruth R., additional

Published
2023
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32. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

Author

Diray-Arce, Joann, primary, Fourati, Slim, additional, Jayavelu, Naresh Doni, additional, Patel, Ravi, additional, Maguire, Cole, additional, Chang, Ana C., additional, Dandekar, Ravi, additional, Qi, Jingjing, additional, Lee, Brian, additional, van Zalm, Patrick, additional, Schroeder, Andrew, additional, Chen, Ernie, additional, Konstorum, Anna, additional, Brito, Anderson, additional, Gygi, Jeremy P., additional, Kho, Alvin, additional, Chen, Jing, additional, Pawar, Shrikant, additional, Gonzalez-Reiche, Ana Silvia, additional, Hoch, Annmarie, additional, Milliren, Carly E., additional, Overton, James A., additional, Westendorf, Kerstin, additional, Cairns, Charles B., additional, Rouphael, Nadine, additional, Bosinger, Steven, additional, Kim-Schulze, Seunghee, additional, Krammer, Florian, additional, Rosen, Lindsey, additional, Grubaugh, Nathan, additional, van Bakel, Harm, additional, Wilson, Michael, additional, Rajan, Jayant, additional, Steen, Hanno, additional, Eckalbar, Walter, additional, Cotsapas, Chris, additional, Langelier, Charles R., additional, Levy, Ofer, additional, Altman, Matthew C., additional, Maecker, Holden, additional, Montgomery, Ruth R., additional, Haddad, Elias K., additional, Sekaly, Rafick P., additional, Esserman, Denise, additional, Ozonoff, Al, additional, Becker, Patrice M., additional, Augustine, Alison D., additional, Guan, Leying, additional, Peters, Bjoern, additional, and Kleinstein, Steven H., additional

Published
2023
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33. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease

Author

Pillai, Padmini S., Molony, Ryan D., Martinod, Kimberly, Dong, Huiping, Pang, Iris K., Tal, Michal C., Solis, Angel G., Bielecki, Piotr, Mohanty, Subhasis, Trentalange, Mark, Homer, Robert J., Flavell, Richard A., Wagner, Denisa D., Montgomery, Ruth R., Shaw, Albert C., Staeheli, Peter, and Iwasaki, Akiko

Published
2016

34. SenNet recommendations for detecting senescent cells in different tissues

Author

Suryadevara, Vidyani, Hudgins, Adam D., Rajesh, Adarsh, Pappalardo, Alberto, Karpova, Alla, Dey, Amit K., Hertzel, Ann, Agudelo, Anthony, Rocha, Azucena, Soygur, Bikem, Schilling, Birgit, Carver, Chase M., Aguayo-Mazzucato, Cristina, Baker, Darren J., Bernlohr, David A., Jurk, Diana, Mangarova, Dilyana B., Quardokus, Ellen M., Enninga, Elizabeth Ann L., Schmidt, Elizabeth L., Chen, Feng, Duncan, Francesca E., Cambuli, Francesco, Kaur, Gagandeep, Kuchel, George A., Lee, Gung, Daldrup-Link, Heike E., Martini, Helene, Phatnani, Hemali, Al-Naggar, Iman M., Rahman, Irfan, Nie, Jia, Passos, João F., Silverstein, Jonathan C., Campisi, Judith, Wang, Julia, Iwasaki, Kanako, Barbosa, Karina, Metis, Kay, Nernekli, Kerem, Niedernhofer, Laura J., Ding, Li, Wang, Lichao, Adams, Lisa C., Ruiyang, Liu, Doolittle, Madison L., Teneche, Marcos G., Schafer, Marissa J., Xu, Ming, Hajipour, Mohammadjavad, Boroumand, Mozhgan, Basisty, Nathan, Sloan, Nicholas, Slavov, Nikolai, Kuksenko, Olena, Robson, Paul, Gomez, Paul T., Vasilikos, Periklis, Adams, Peter D., Carapeto, Priscila, Zhu, Quan, Ramasamy, Ramalakshmi, Perez-Lorenzo, Rolando, Fan, Rong, Dong, Runze, Montgomery, Ruth R., Shaikh, Sadiya, Vickovic, Sanja, Yin, Shanshan, Kang, Shoukai, Suvakov, Sonja, Khosla, Sundeep, Garovic, Vesna D., Menon, Vilas, Xu, Yanxin, Song, Yizhe, Suh, Yousin, Dou, Zhixun, and Neretti, Nicola

Abstract

Once considered a tissue culture-specific phenomenon, cellular senescence has now been linked to various biological processes with both beneficial and detrimental roles in humans, rodents and other species. Much of our understanding of senescent cell biology still originates from tissue culture studies, where each cell in the culture is driven to an irreversible cell cycle arrest. By contrast, in tissues, these cells are relatively rare and difficult to characterize, and it is now established that fully differentiated, postmitotic cells can also acquire a senescence phenotype. The SenNet Biomarkers Working Group was formed to provide recommendations for the use of cellular senescence markers to identify and characterize senescent cells in tissues. Here, we provide recommendations for detecting senescent cells in different tissues based on a comprehensive analysis of existing literature reporting senescence markers in 14 tissues in mice and humans. We discuss some of the recent advances in detecting and characterizing cellular senescence, including molecular senescence signatures and morphological features, and the use of circulating markers. We aim for this work to be a valuable resource for both seasoned investigators in senescence-related studies and newcomers to the field.

Published
2024
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35. Featured Cover

Author

Konstorum, Anna, primary, Mohanty, Subhasis, additional, Zhao, Yujiao, additional, Melillo, Anthony, additional, Vander Wyk, Brent, additional, Nelson, Allison, additional, Tsang, Sui, additional, Blevins, Tamara P., additional, Belshe, Robert B., additional, Chawla, Daniel G., additional, Rondina, Matthew T., additional, Gill, Thomas M., additional, Montgomery, Ruth R., additional, Allore, Heather G., additional, Kleinstein, Steven H., additional, and Shaw, Albert C., additional

Published
2023
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36. Platelet response to influenza vaccination reflects effects of aging

Author

Konstorum, Anna, primary, Mohanty, Subhasis, additional, Zhao, Yujiao, additional, Melillo, Anthony, additional, Vander Wyk, Brent, additional, Nelson, Allison, additional, Tsang, Sui, additional, Blevins, Tamara P., additional, Belshe, Robert B., additional, Chawla, Daniel G., additional, Rondina, Matthew T., additional, Gill, Thomas M., additional, Montgomery, Ruth R., additional, Allore, Heather G., additional, Kleinstein, Steven H., additional, and Shaw, Albert C., additional

Published
2023
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37. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection

Author

Asashima, Hiromitsu, primary, Mohanty, Subhasis, additional, Comi, Michela, additional, Ruff, William E., additional, Hoehn, Kenneth B., additional, Wong, Patrick, additional, Klein, Jon, additional, Lucas, Carolina, additional, Cohen, Inessa, additional, Coffey, Sarah, additional, Lele, Nikhil, additional, Greta, Leissa, additional, Raddassi, Khadir, additional, Chaudhary, Omkar, additional, Unterman, Avraham, additional, Emu, Brinda, additional, Kleinstein, Steven H., additional, Montgomery, Ruth R., additional, Iwasaki, Akiko, additional, Dela Cruz, Charles S., additional, Kaminski, Naftali, additional, Shaw, Albert C., additional, Hafler, David A., additional, and Sumida, Tomokazu S., additional

Published
2023
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38. Longitudinal serum proteomics analyses identify unique and overlapping host response pathways in Lyme disease and West Nile virus infection

Author

Boada, Patrick, primary, Fatou, Benoit, additional, Belperron, Alexia A., additional, Sigdel, Tara K., additional, Smolen, Kinga K., additional, Wurie, Zainab, additional, Levy, Ofer, additional, Ronca, Shannon E., additional, Murray, Kristy O., additional, Liberto, Juliane M., additional, Rashmi, Priyanka, additional, Kerwin, Maggie, additional, Montgomery, Ruth R., additional, Bockenstedt, Linda K., additional, Steen, Hanno, additional, and Sarwal, Minnie M., additional

Published
2022
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39. Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis

Author

Hwang, Seong-Hye, Jung, Seung-Hyun, Lee, Saseong, Choi, Susanna, Yoo, Seung-Ah, Park, Ji-Hwan, Hwang, Daehee, Shim, Seung Cheol, Sabbagh, Laurent, Kim, Ki-Jo, Park, Sung Hwan, Cho, Chul-Soo, Kim, Bong-Sung, Leng, Lin, Montgomery, Ruth R., Bucala, Richard, Chung, Yeun-Jun, and Kim, Wan-Uk

Published
2015

40. Analytical Approaches to Uncover Genetic Associations for Rare Outcomes: Lessons from West Nile Neuroinvasive Disease

Author

Cahill, Megan E. and Montgomery, Ruth R.

Subjects
Incidence, Humans, West Nile virus, Article, West Nile Fever
Abstract

West Nile viral infection causes severe neuroinvasive disease in less than one percent of infected humans. There are no targeted therapeutics for this serious and potentially fatal disease, and to date no vaccine has been approved for humans. With climate change expected to result in rising incidence of West Nile and other related vector-borne viral infections, there is an increasing need to identify those at risk for serious disease and potential leads for therapeutic and vaccine development. Genetic variation, particularly in genes whose products are either directly or indirectly connected to immune response to infections, is a critical avenue of investigation to identify those at higher risk of clinically apparent West Nile infection. Given the small percent of infections that progress to severe disease and the relatively low numbers of reported infections, it is challenging to conduct well-powered studies to identify genetic factors associated with more severe outcomes. In this chapter, we outline several approaches with the objective to take full advantage of all available data in order to identify genetic factors which lead to increased risk of severe West Nile neuroinvasive disease. These methods are generalizable to other conditions with limited cohort size and rare outcomes.

Published
2022

41. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study

Author

Ozonoff, Al, primary, Schaenman, Joanna, additional, Jayavelu, Naresh Doni, additional, Milliren, Carly E., additional, Calfee, Carolyn S., additional, Cairns, Charles B., additional, Kraft, Monica, additional, Baden, Lindsey R., additional, Shaw, Albert C., additional, Krammer, Florian, additional, van Bakel, Harm, additional, Esserman, Denise A., additional, Liu, Shanshan, additional, Sesma, Ana Fernandez, additional, Simon, Viviana, additional, Hafler, David A., additional, Montgomery, Ruth R., additional, Kleinstein, Steven H., additional, Levy, Ofer, additional, Bime, Christian, additional, Haddad, Elias K., additional, Erle, David J., additional, Pulendran, Bali, additional, Nadeau, Kari C., additional, Davis, Mark M., additional, Hough, Catherine L., additional, Messer, William B., additional, Higuita, Nelson I. Agudelo, additional, Metcalf, Jordan P., additional, Atkinson, Mark A., additional, Brakenridge, Scott C., additional, Corry, David, additional, Kheradmand, Farrah, additional, Ehrlich, Lauren I.R., additional, Melamed, Esther, additional, McComsey, Grace A., additional, Sekaly, Rafick, additional, Diray-Arce, Joann, additional, Peters, Bjoern, additional, Augustine, Alison D., additional, Reed, Elaine F., additional, Altman, Matthew C., additional, Becker, Patrice M., additional, Rouphael, Nadine, additional, Ozonoff, Al, additional, Bime, Chris, additional, Davis, Mark M, additional, McEnaney, Kerry, additional, Barton, Brenda, additional, Lentucci, Claudia, additional, Saluvan, Mehmet, additional, Chang, Ana C., additional, Hoch, Annmarie, additional, Albert, Marisa, additional, Shaheen, Tanzia, additional, Kho, Alvin T., additional, Thomas, Sanya, additional, Chen, Jing, additional, Murphy, Maimouna D., additional, Cooney, Mitchell, additional, Presnell, Scott, additional, Fragiadakis, Gabriela K., additional, Patel, Ravi, additional, Guan, Leying, additional, Gygi, Jeremy, additional, Pawar, Shrikant, additional, Brito, Anderson, additional, Khalil, Zain, additional, Maguire, Cole, additional, Fourati, Slim, additional, Overton, James A., additional, Vita, Randi, additional, Westendorf, Kerstin, additional, Salehi-Rad, Ramin, additional, Leligdowicz, Aleksandra, additional, Matthay, Michael A., additional, Singer, Jonathan P., additional, Kangelaris, Kirsten N., additional, Hendrickson, Carolyn M., additional, Krummel, Matthew F., additional, Langelier, Charles R., additional, Woodruff, Prescott G., additional, Powell, Debra L., additional, Kim, James N., additional, Simmons, Brent, additional, Goonewardene, I. Michael, additional, Smith, Cecilia M., additional, Martens, Mark, additional, Mosier, Jarrod, additional, Kimura, Hiroki, additional, Sherman, Amy C., additional, Walsh, Stephen R., additional, Issa, Nicolas C., additional, Dela Cruz, Charles, additional, Farhadian, Shelli, additional, Iwasaki, Akiko, additional, Ko, Albert I., additional, Chinthrajah, Sharon, additional, Ahuja, Neera, additional, Rogers, Angela J., additional, Artandi, Maja, additional, Siegel, Sarah A.R., additional, Lu, Zhengchun, additional, Drevets, Douglas A., additional, Brown, Brent R., additional, Anderson, Matthew L., additional, Guirgis, Faheem W., additional, Thyagarajan, Rama V., additional, Rousseau, Justin F., additional, Wylie, Dennis, additional, Busch, Johanna, additional, Gandhi, Saurin, additional, Triplett, Todd A., additional, Yendewa, George, additional, Giddings, Olivia, additional, Anderson, Evan J., additional, Mehta, Aneesh K., additional, Sevransky, Jonathan E., additional, Khor, Bernard, additional, Rahman, Adeeb, additional, Stadlbauer, Daniel, additional, Dutta, Jayeeta, additional, Xie, Hui, additional, Kim-Schulze, Seunghee, additional, Gonzalez-Reiche, Ana Silvia, additional, van de Guchte, Adriana, additional, Farrugia, Keith, additional, Khan, Zenab, additional, Maecker, Holden T., additional, Elashoff, David, additional, Brook, Jenny, additional, Ramires-Sanchez, Estefania, additional, Llamas, Megan, additional, Rivera, Adreanne, additional, Perdomo, Claudia, additional, Ward, Dawn C., additional, Magyar, Clara E., additional, Fulcher, Jennifer A., additional, Abe-Jones, Yumiko, additional, Asthana, Saurabh, additional, Beagle, Alexander, additional, Bhide, Sharvari, additional, Carrillo, Sidney A., additional, Chak, Suzanna, additional, Ghale, Rajani, additional, Gonzalez, Ana, additional, Jauregui, Alejandra, additional, Jones, Norman, additional, Lea, Tasha, additional, Lee, Deanna, additional, Lota, Raphael, additional, Milush, Jeff, additional, Nguyen, Viet, additional, Pierce, Logan, additional, Prasad, Priya A., additional, Rao, Arjun, additional, Samad, Bushra, additional, Shaw, Cole, additional, Sigman, Austin, additional, Sinha, Pratik, additional, Ward, Alyssa, additional, Willmore, Andrew, additional, Zhan, Jenny, additional, Rashid, Sadeed, additional, Rodriguez, Nicklaus, additional, Tang, Kevin, additional, Altamirano, Luz Torres, additional, Betancourt, Legna, additional, Curiel, Cindy, additional, Sutter, Nicole, additional, Paz, Maria Tercero, additional, Tietje-Ulrich, Gayelan, additional, Leroux, Carolyn, additional, Connors, Jennifer, additional, Bernui, Mariana, additional, Kutzler, Michel A., additional, Edwards, Carolyn, additional, Lee, Edward, additional, Lin, Edward, additional, Croen, Brett, additional, Semenza, Nicholas C., additional, Rogowski, Brandon, additional, Melnyk, Nataliya, additional, Woloszczuk, Kyra, additional, Cusimano, Gina, additional, Bell, Mathew R., additional, Furukawa, Sara, additional, McLin, Renee, additional, Marrero, Pamela, additional, Sheidy, Julie, additional, Tegos, George P., additional, Nagle, Crystal, additional, Mege, Nathan, additional, Ulring, Kristen, additional, Seyfert-Margolis, Vicki, additional, Conway, Michelle, additional, Francisco, Dave, additional, Molzahn, Allyson, additional, Erickson, Heidi, additional, Wilson, Connie Cathleen, additional, Schunk, Ron, additional, Sierra, Bianca, additional, Hughes, Trina, additional, Smolen, Kinga, additional, Desjardins, Michael, additional, van Haren, Simon, additional, Mitre, Xhoi, additional, Cauley, Jessica, additional, Li, Xiaofang, additional, Tong, Alexandra, additional, Evans, Bethany, additional, Montesano, Christina, additional, Licona, Jose Humberto, additional, Krauss, Jonathan, additional, Chang, Jun Bai Park, additional, Izaguirre, Natalie, additional, Chaudhary, Omkar, additional, Coppi, Andreas, additional, Fournier, John, additional, Mohanty, Subhasis, additional, Muenker, M. Catherine, additional, Nelson, Allison, additional, Raddassi, Khadir, additional, Rainone, Michael, additional, Ruff, William E., additional, Salahuddin, Syim, additional, Schulz, Wade L., additional, Vijayakumar, Pavithra, additional, Wang, Haowei, additional, Wunder Jr., Elsio, additional, Young, H. Patrick, additional, Zhao, Yujiao, additional, Saksena, Miti, additional, Altman, Deena, additional, Kojic, Erna, additional, Srivastava, Komal, additional, Eaker, Lily Q., additional, Bermúdez-González, Maria C., additional, Beach, Katherine F., additional, Sominsky, Levy A., additional, Azad, Arman R., additional, Carreño, Juan Manuel, additional, Singh, Gagandeep, additional, Raskin, Ariel, additional, Tcheou, Johnstone, additional, Bielak, Dominika, additional, Kawabata, Hisaaki, additional, Mulder, Lubbertus CF, additional, Kleiner, Giulio, additional, Lee, Alexandra S., additional, Do, Evan Do, additional, Fernandes, Andrea, additional, Manohar, Monali, additional, Hagan, Thomas, additional, Blish, Catherine A., additional, Din, Hena Naz, additional, Roque, Jonasel, additional, Yang, Samuel, additional, Brunton, Amanda, additional, Sullivan, Peter E., additional, Strnad, Matthew, additional, Lyski, Zoe L., additional, Coulter, Felicity J., additional, Booth, J. Leland, additional, Sinko, Lauren A., additional, Moldawer, Lyle L., additional, Borresen, Brittany, additional, Roth-Manning, Brittney, additional, Song, Li-Zhen, additional, Nelson, Ebony, additional, Lewis-Smith, Megan, additional, Smith, Jacob, additional, Tipan, Pablo Guaman, additional, Siles, Nadia, additional, Bazzi, Sam, additional, Geltman, Janelle, additional, Hurley, Kerin, additional, Gabriele, Gio, additional, Sieg, Scott, additional, Vaysman, Tatyana, additional, Bristow, Laurel, additional, Hussaini, Laila, additional, Hellmeister, Kieffer, additional, Samaha, Hady, additional, Cheng, Andrew, additional, Spainhour, Christine, additional, Scherer, Erin M., additional, Johnson, Brandi, additional, Bechnak, Amer, additional, Ciric, Caroline R., additional, Hewitt, Lauren, additional, Carter, Erin, additional, Mcnair, Nina, additional, Panganiban, Bernadine, additional, Huerta, Christopher, additional, Usher, Jacob, additional, and Ribeiro, Susan Pereira, additional

Published
2022
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46. Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells

Author

Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Chemistry, Koch Institute for Integrative Cancer Research at MIT, Jiang, Ruoyi, Meng, Hailong, Raddassi, Khadir, Fleming, Ira, Hoehn, Kenneth B, Dardick, Kenneth R, Belperron, Alexia A, Montgomery, Ruth R, Shalek, Alex K, Hafler, David A, Kleinstein, Steven H, Bockenstedt, Linda K, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Chemistry, Koch Institute for Integrative Cancer Research at MIT, Jiang, Ruoyi, Meng, Hailong, Raddassi, Khadir, Fleming, Ira, Hoehn, Kenneth B, Dardick, Kenneth R, Belperron, Alexia A, Montgomery, Ruth R, Shalek, Alex K, Hafler, David A, Kleinstein, Steven H, and Bockenstedt, Linda K

Abstract

The skin lesion erythema migrans (EM) is an initial sign of the Ixodes tick-transmitted Borreliella spirochetal infection known as Lyme disease. T cells and innate immune cells have previously been shown to predominate the EM lesion and promote the reaction. Despite the established importance of B cells and antibodies in preventing infection, the role of B cells in the skin immune response to Borreliella is unknown. Here, we used single-cell RNA-Seq in conjunction with B cell receptor (BCR) sequencing to immunophenotype EM lesions and their associated B cells and BCR repertoires. We found that B cells were more abundant in EM in comparison with autologous uninvolved skin; many were clonally expanded and had circulating relatives. EM-associated B cells upregulated the expression of MHC class II genes and exhibited preferential IgM isotype usage. A subset also exhibited low levels of somatic hypermutation despite a gene expression profile consistent with memory B cells. Our study demonstrates that single-cell gene expression with paired BCR sequencing can be used to interrogate the sparse B cell populations in human skin and reveals that B cells in the skin infection site in early Lyme disease expressed a phenotype consistent with local antigen presentation and antibody production.

Published
2022

47. Platelet response to influenza vaccination reflects effects of aging

Author

Konstorum, Anna, primary, Mohanty, Subhasis, additional, Zhao, Yujiao, additional, Melillo, Anthony, additional, Vander Wyk, Brent, additional, Nelson, Allison, additional, Tsang, Sui, additional, Blevins, Tamara P., additional, Belshe, Robert B., additional, Chawla, Daniel G., additional, Rondina, Matthew T., additional, Montgomery, Ruth R., additional, Allore, Heather G., additional, Kleinstein, Steven H., additional, and Shaw, Albert C., additional

Published
2022
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