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Last built using PubMed API : 2023-09-26 18:31
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Immport Dataset Available (34)
Columbia University (44)
HIPC 2 (2015) (356)
HIPC 3 (2022) (99)
Icahn School of Medicine at Mount Sinai (10)
La Jolla Institute for Immunology (47)
Massachusetts Institute of technology (6)
Seattle Children's Research Institute (19)
Stanford (30)
Yale University (29)
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Solomon BD, Zheng H, Dillon LW, Goldman JD, Hourigan CS, Heath JR, Khatri P
Frontiers in immunology. 2023-09-21
PMID: 37180102
Genotype
HIPC 3 (2022)
Histocompatibility Antigens Class I
Histocompatibility Antigens Class II
HLA Antigens
Humans
Sequence Analysis, DNA
Stanford
Transcriptome
Abstract:
The human leukocyte antigen (HLA) locus plays a central role in adaptive immune function and has significant clinical implications for tissue transplant compatibility and allelic disease associations. Studies using bulk-cell RNA sequencing have demonstrated that HLA transcription may be regulated in an allele-specific manner and single-cell RNA sequencing (scRNA-seq) has the potential to better characterize these expression patterns. However, quantification of allele-specific expression (ASE) for HLA loci requires sample-specific reference genotyping due to extensive polymorphism. While genotype prediction from bulk RNA sequencing is well described, the feasibility of predicting HLA genotypes directly from single-cell data is unknown. Here we evaluate and expand upon several computational HLA genotyping tools by comparing predictions from human single-cell data to gold-standard, molecular genotyping. The highest 2-field accuracy averaged across all loci was 76% by arcasHLA and increased to 86% using a composite model of multiple genotyping tools. We also developed a highly accurate model (AUC 0.93) for predicting HLA-DRB345 copy number in order to improve genotyping accuracy of the HLA-DRB locus. Genotyping accuracy improved with read depth and was reproducible at repeat sampling. Using a metanalytic approach, we also show that HLA genotypes from PHLAT and OptiType can generate ASE ratios that are highly correlated (R2 = 0.8 and 0.94, respectively) with those derived from gold-standard genotyping.
Ockene MW, Russo SC, Lee H, Monthé-Drèze C, Stanley TL, Ma IL, Toribio M, Shook LL, Grinspoon SK, Edlow AG, Fourman LT
The Journal of clinical endocrinology and metabolism. 2023-09-19
PMID: 36988326
Birth Weight
Body Mass Index
Cardiovascular Diseases
Child
COVID-19
Female
HIPC 3 (2022)
Humans
Infant
Infant, Newborn
Longitudinal Studies
Massachusetts Institute of technology
Pregnancy
Weight Gain
Abstract:
[{'@Label': 'CONTEXT', '#text': 'Since the initial outbreak of coronavirus disease 2019 (COVID-19), a novel population of children with in utero exposure to maternal infection has emerged whose health outcomes are largely unknown.'}, {'@Label': 'OBJECTIVE', '#text': 'To compare longitudinal growth trajectories among infants with vs without in utero COVID-19 exposure.'}, {'@Label': 'METHODS', '#text': 'We conducted a longitudinal cohort study leveraging a prospectively enrolled perinatal biorepository among 149 infants with in utero COVID-19 exposure and 127 unexposed controls. Weight, length, and body mass index (BMI) were abstracted from health records at 0, 2, 6, and 12 months and standardized using World Health Organization growth charts. Analyses were adjusted for maternal age, ethnicity, parity, insurance, and BMI as well as infant sex, birthdate, and breastfeeding.'}, {'@Label': 'RESULTS', '#text': 'Infants with in utero COVID-19 exposure vs controls exhibited differential trajectories of weight and BMI, but not length, z-score over the first year of life (study group × time interaction, P < .0001 for weight and BMI). Infants born to mothers with prenatal COVID-19 had lower BMI z-score at birth (effect size: -0.35, 95% CI -0.66 to -0.03) and greater gain in BMI z-score from birth to 12 months (effect size: 0.53, 95% CI 0.06 to 0.99). Birth weight z-score mediated a significant proportion of the relationship between COVID-19 exposure and postnatal growth (estimate ± SE, 32 ± 14%, P = .02).'}, {'@Label': 'CONCLUSION', '#text': 'Infants with in utero COVID-19 exposure exhibited lower birth weight and accelerated weight gain in the first year of life, which may be harbingers of downstream cardiometabolic pathology. Further studies are needed to delineate cardiometabolic sequelae among this emerging global population.'}]
Gygi JP, Kleinstein SH, Guan L
Human vaccines & immunotherapeutics. 2023-09-13
PMID: 37697867
HIPC 3 (2022)
Machine Learning
Vaccination
Yale University
Abstract:
Overfitting describes the phenomenon where a highly predictive model on the training data generalizes poorly to future observations. It is a common concern when applying machine learning techniques to contemporary medical applications, such as predicting vaccination response and disease status in infectious disease or cancer studies. This review examines the causes of overfitting and offers strategies to counteract it, focusing on model complexity reduction, reliable model evaluation, and harnessing data diversity. Through discussion of the underlying mathematical models and illustrative examples using both synthetic data and published real datasets, our objective is to equip analysts and bioinformaticians with the knowledge and tools necessary to detect and mitigate overfitting in their research.
Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre NC, Lutz R, Cruz I, Raddassi K, Ruff WE, Racke MK, Wilson JE, Givens TS, Grifoni A, Weiskopf D, Sette A, Kleinstein SH, Montgomery RR, Shaw AC, Li F, Fan R, Hafler DA, Tomayko MM, Longbrake EE
JCI insight. 2023-08-23
PMID: 37606046
Aged
Antibodies, Monoclonal
Antibody Formation
Antilymphocyte Serum
BNT162 Vaccine
COVID-19
HIPC 3 (2022)
Humans
RNA, Messenger
SARS-CoV-2
Vaccination
Yale University
Abstract:
BACKGROUNDWhile B cell depletion is associated with attenuated antibody responses to SARS-CoV-2 mRNA vaccination, responses vary among individuals. Thus, elucidating the factors that affect immune responses after repeated vaccination is an important clinical need.METHODSWe evaluated the quality and magnitude of the T cell, B cell, antibody, and cytokine responses to a third dose of BNT162b2 or mRNA-1273 mRNA vaccine in patients with B cell depletion.RESULTSIn contrast with control individuals (n = 10), most patients on anti-CD20 therapy (n = 48) did not demonstrate an increase in spike-specific B cells or antibodies after a third dose of vaccine. A third vaccine elicited significantly increased frequencies of spike-specific non-naive T cells. A small subset of B cell-depleted individuals effectively produced spike-specific antibodies, and logistic regression models identified time since last anti-CD20 treatment and lower cumulative exposure to anti-CD20 mAbs as predictors of those having a serologic response. B cell-depleted patients who mounted an antibody response to 3 vaccine doses had persistent humoral immunity 6 months later.CONCLUSIONThese results demonstrate that serial vaccination strategies can be effective for a subset of B cell-depleted patients.FUNDINGThe NIH (R25 NS079193, P01 AI073748, U24 AI11867, R01 AI22220, UM 1HG009390, P01 AI039671, P50 CA121974, R01 CA227473, U01CA260507, 75N93019C00065, K24 AG042489), NIH HIPC Consortium (U19 AI089992), the National Multiple Sclerosis Society (CA 1061-A-18, RG-1802-30153), the Nancy Taylor Foundation for Chronic Diseases, Erase MS, and the Claude D. Pepper Older Americans Independence Center at Yale (P30 AG21342).
Mayer-Blackwell K, Ryu H, Codd AS, Parks KR, MacMillan HR, Cohen KW, Stewart TL, Seese A, Lemos MP, De Rosa SC, Czartoski JL, Moodie Z, Nguyen LT, McGuire DJ, Ahmed R, Fiore-Gartland A, McElrath MJ, Newell EW
Cell reports. Medicine. 2023-08-18
PMID: 37552991
CD8-Positive T-Lymphocytes
COVID-19
Epitopes
HIPC 3 (2022)
Humans
Leukocyte Common Antigens
Memory T Cells
SARS-CoV-2
Seattle Children's Research Institute
Vaccination
Abstract:
SARS-CoV-2 infection and mRNA vaccination both elicit spike (S)-specific T cell responses. To analyze how T cell memory from prior infection influences T cell responses to vaccination, we evaluated functional T cell responses in naive and previously infected vaccine recipients. Pre-vaccine S-specific responses are predictive of subsequent CD8+ T cell vaccine-response magnitudes. Comparing baseline with post-vaccination TCRβ repertoires, we observed large clonotypic expansions correlated with the frequency of spike-specific T cells. Epitope mapping the largest CD8+ T cell responses confirms that an HLA-A∗03:01 epitope was highly immunodominant. Peptide-MHC tetramer staining together with mass cytometry and single-cell sequencing permit detailed phenotyping and clonotypic tracking of these S-specific CD8+ T cells. Our results demonstrate that infection-induced S-specific CD8+ T cell memory plays a significant role in shaping the magnitude and clonal composition of the circulating T cell repertoire after vaccination, with mRNA vaccination promoting CD8+ memory T cells to a TEMRA-like phenotype.
Sulczewski FB, Maqueda-Alfaro RA, Alcántara-Hernández M, Perez OA, Saravanan S, Yun TJ, Seong D, Arroyo Hornero R, Raquer-McKay HM, Esteva E, Lanzar ZR, Leylek RA, Adams NM, Das A, Rahman AH, Gottfried-Blackmore A, Reizis B, Idoyaga J
Nature immunology. 2023-08-14
PMID: 37414907
Animals
Antiviral Agents
Bone Marrow
Cell Differentiation
Columbia University
Dendritic Cells
HIPC 3 (2022)
Mice
Abstract:
High-dimensional approaches have revealed heterogeneity amongst dendritic cells (DCs), including a population of transitional DCs (tDCs) in mice and humans. However, the origin and relationship of tDCs to other DC subsets has been unclear. Here we show that tDCs are distinct from other well-characterized DCs and conventional DC precursors (pre-cDCs). We demonstrate that tDCs originate from bone marrow progenitors shared with plasmacytoid DCs (pDCs). In the periphery, tDCs contribute to the pool of ESAM+ type 2 DCs (DC2s), and these DC2s have pDC-related developmental features. Different from pre-cDCs, tDCs have less turnover, capture antigen, respond to stimuli and activate antigen-specific naïve T cells, all characteristics of differentiated DCs. Different from pDCs, viral sensing by tDCs results in IL-1β secretion and fatal immune pathology in a murine coronavirus model. Our findings suggest that tDCs are a distinct pDC-related subset with a DC2 differentiation potential and unique proinflammatory function during viral infections.
Matsumoto R, Gray J, Rybkina K, Oppenheimer H, Levy L, Friedman LM, Khamaisi M, Meng W, Rosenfeld AM, Guyer RS, Bradley MC, Chen D, Atkinson MA, Brusko TM, Brusko M, Connors TJ, Luning Prak ET, Hershberg U, Sims PA, Hertz T, Farber DL
Nature immunology. 2023-07-31
PMID: 37460638
Adult
B-Lymphocytes
Bronchi
Child
Child, Preschool
Columbia University
COVID-19
HIPC 3 (2022)
Humans
Infant
Lymph Nodes
Lymphoid Tissue
Abstract:
Infants and young children are more susceptible to common respiratory pathogens than adults but can fare better against novel pathogens like severe acute respiratory syndrome coronavirus 2. The mechanisms by which infants and young children mount effective immune responses to respiratory pathogens are unknown. Through investigation of lungs and lung-associated lymph nodes from infant and pediatric organ donors aged 0-13 years, we show that bronchus-associated lymphoid tissue (BALT), containing B cell follicles, CD4+ T cells and functionally active germinal centers, develop during infancy. BALT structures are prevalent around lung airways during the first 3 years of life, and their numbers decline through childhood coincident with the accumulation of memory T cells. Single-cell profiling and repertoire analysis reveals that early life lung B cells undergo differentiation, somatic hypermutation and immunoglobulin class switching and exhibit a more activated profile than lymph node B cells. Moreover, B cells in the lung and lung-associated lymph nodes generate biased antibody responses to multiple respiratory pathogens compared to circulating antibodies, which are mostly specific for vaccine antigens in the early years of life. Together, our findings provide evidence for BALT as an early life adaptation for mobilizing localized immune protection to the diverse respiratory challenges during this formative life stage.
Rodriguez OL, Safonova Y, Silver CA, Shields K, Gibson WS, Kos JT, Tieri D, Ke H, Jackson KJL, Boyd SD, Smith ML, Marasco WA, Watson CT
Nature communications. 2023-07-24
PMID: 37479682
Alleles
Genes, Immunoglobulin
Genes, Immunoglobulin Heavy Chain
Germ-Line Mutation
HIPC 3 (2022)
Humans
Immunoglobulin Heavy Chains
Stanford
Abstract:
Variation in the antibody response has been linked to differential outcomes in disease, and suboptimal vaccine and therapeutic responsiveness, the determinants of which have not been fully elucidated. Countering models that presume antibodies are generated largely by stochastic processes, we demonstrate that polymorphisms within the immunoglobulin heavy chain locus (IGH) impact the naive and antigen-experienced antibody repertoire, indicating that genetics predisposes individuals to mount qualitatively and quantitatively different antibody responses. We pair recently developed long-read genomic sequencing methods with antibody repertoire profiling to comprehensively resolve IGH genetic variation, including novel structural variants, single nucleotide variants, and genes and alleles. We show that IGH germline variants determine the presence and frequency of antibody genes in the expressed repertoire, including those enriched in functional elements linked to V(D)J recombination, and overlapping disease-associated variants. These results illuminate the power of leveraging IGH genetics to better understand the regulation, function, and dynamics of the antibody response in disease.
Sayed N, Huang Y, Nguyen K, Krejciova-Rajaniemi Z, Grawe AP, Gao T, Tibshirani R, Hastie T, Alpert A, Cui L, Kuznetsova T, Rosenberg-Hasson Y, Ostan R, Monti D, Lehallier B, Shen-Orr SS, Maecker HT, Dekker CL, Wyss-Coray T, Franceschi C, Jojic V, Haddad F, Montoya JG, Wu JC, Davis MM, ...
Nature aging. 2023-07-19
PMID: 34888528
Aged, 80 and over
Aging
Animals
Deep Learning
Endothelial Cells
Frailty
HIPC 2 (2015)
Humans
Immunosenescence
Inflammation
Mice
Multimorbidity
Abstract:
While many diseases of aging have been linked to the immunological system, immune metrics capable of identifying the most at-risk individuals are lacking. From the blood immunome of 1,001 individuals aged 8-96 years, we developed a deep-learning method based on patterns of systemic age-related inflammation. The resulting inflammatory clock of aging (iAge) tracked with multimorbidity, immunosenescence, frailty and cardiovascular aging, and is also associated with exceptional longevity in centenarians. The strongest contributor to iAge was the chemokine CXCL9, which was involved in cardiac aging, adverse cardiac remodeling and poor vascular function. Furthermore, aging endothelial cells in human and mice show loss of function, cellular senescence and hallmark phenotypes of arterial stiffness, all of which are reversed by silencing CXCL9. In conclusion, we identify a key role of CXCL9 in age-related chronic inflammation and derive a metric for multimorbidity that can be utilized for the early detection of age-related clinical phenotypes.
Montgomery RR, Steen H
Nature aging. 2023-07-19
PMID: 36970123
Archives
Big Data
COVID-19
Healthy Aging
HIPC 2 (2015)
Humans
Proteomics
Abstract:
Arthur et al. leverage different types of big data, either generated in house from cohorts of healthy aging and COVID-19, or downloaded from the ever-increasing public data archives, to disentangle the distinct cellular and proteomic mechanisms of COVID-19 and aging.
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