Andrew McDavid
A5063304924- Single-cell and spatial transcriptomics
- Genetic Associations and Epidemiology
- Alzheimer's disease research and treatments
- Bioinformatics and Genomic Networks
- T-cell and B-cell Immunology
- Gene expression and cancer classification
- Neonatal Respiratory Health Research
- Pediatric health and respiratory diseases
- Immune Cell Function and Interaction
- Gene Regulatory Network Analysis
- Systemic Lupus Erythematosus Research
- Congenital Diaphragmatic Hernia Studies
- Infant Health and Development
- Immune cells in cancer
- Gut microbiota and health
- Child and Adolescent Health
- Genomic variations and chromosomal abnormalities
- Cancer Genomics and Diagnostics
- Cell Image Analysis Techniques
- RNA modifications and cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Molecular Biology Techniques and Applications
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Bone and Joint Diseases
University of Rochester
2018-2025
University of Rochester Medical Center
2018-2024
Fred Hutch Cancer Center
2012-2023
Museum of Heilongjiang Province
2021
University of Washington
2012-2019
University of Copenhagen
2019
Health and Human Development (2HD) Research Network
2019
RELX Group (United States)
2019
USF Health Byrd Alzheimer's Institute
2019
University of South Florida
2019
Single-cell transcriptomics reveals gene expression heterogeneity but suffers from stochastic dropout and characteristic bimodal distributions in which is either strongly non-zero or non-detectable. We propose a two-part, generalized linear model for such data that parameterizes both of these features. argue the cellular detection rate, fraction genes expressed cell, should be adjusted as source nuisance variation. Our provides set enrichment analysis tailored to single-cell data. It...
Abstract Motivation: Cell populations are never truly homogeneous; individual cells exist in biochemical states that define functional differences between them. New technology based on microfluidic arrays combined with multiplexed quantitative polymerase chain reactions now enables high-throughput single-cell gene expression measurement, allowing assessment of cellular heterogeneity. However, few analytic tools have been developed specifically for the statistical and analytical challenges...
Genome-wide association studies (GWAS) are being conducted at an unprecedented rate in population-based cohorts and have increased our understanding of the pathophysiology complex disease. Regardless context, practical utility this information will ultimately depend upon quality original data. Quality control (QC) procedures for GWAS computationally intensive, operationally challenging, constantly evolving. Here we enumerate some challenges QC data describe approaches that electronic MEdical...
T cell-derived pro-inflammatory cytokines are a major driver of rheumatoid arthritis (RA) pathogenesis. Although these have traditionally been attributed to CD4 cells, we found that CD8 cells notably abundant in synovium and make more interferon (IFN)-γ nearly as much tumor necrosis factor (TNF) their cell counterparts. Furthermore, using unbiased high-dimensional single-cell RNA-seq flow cytometric data, the vast majority synovial tissue fluid belong an effector population characterized by...
Conventional memory CD8+ T cells and mucosal-associated invariant (MAIT cells) are found in blood, liver, mucosal tissues have similar effector potential following activation, specifically expression of IFN-γ granzyme B. To better understand each subset's unique contributions to immunity pathology, we interrogated inflammation- TCR-driven activation requirements using human MAIT isolated from blood tissue biopsies ex vivo functional assays single cell gene experiments. We that had a robust B...
The bone marrow microenvironment contributes to the regulation of hematopoietic stem cell (HSC) function, though its role in age-associated lineage skewing is poorly understood. Here we show that dysfunction aged macrophages (Mφs) directs HSC platelet bias. Mφs from mice and humans exhibited an activated phenotype, with increased expression inflammatory signals. Aged also displayed decreased phagocytic function. Senescent neutrophils, typically cleared by Mφs, were markedly mice, consistent...
Postnatal development of early life microbiota influences immunity, metabolism, neurodevelopment, and infant health. Microbiome occurs at multiple body sites, with distinct community compositions functions. Associations between sites represent an unexplored influence on the microbiome. Here, we examined co-occurrence patterns gut respiratory in pre- full-term infants over first year life, a period critical to neonatal development. Gut collected as longitudinal rectal, throat, nasal samples...
Abstract Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA repertoire sequencing on paired synovial tissue blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + cells, including CCL5+ cells peripheral helper (Tph) which show a prominent transcriptomic signature of recent activation effector function. CD8 higher oligoclonality than with the largest clones enriched in GZMK+ possibly...
Abstract Synovial tissue inflammation is a hallmark of rheumatoid arthritis (RA). Recent work has identified prominent pathogenic cell states in inflamed RA synovial tissue, such as T peripheral helper cells; however, the epigenetic regulation these yet to be defined. Here, we examine genome-wide open chromatin at single-cell resolution 30 samples, including 12 samples with transcriptional data multimodal experiments. We identify 24 classes and predict their associated transcription factors,...
Abstract Genome‐wide association studies (GWAS) are a useful approach in the study of genetic components complex phenotypes. Aside from large cohorts, GWAS have generally been limited to one or few diseases traits. The emergence biobanks linked electronic medical records (EMRs) allows efficient reuse data yield meaningful genotype–phenotype associations for multiple phenotypes Phase I MEdical Records and GEnomics (eMERGE‐I) Network is National Human Genome Research Institute‐supported...
Rheumatoid arthritis (RA) is characterized by the activation of B cells that produce anti-citrullinated protein antibodies (ACPAs) and rheumatoid factors (RFs), but mechanisms which tolerance broken in these remain incompletely understood. We undertook this study to investigate whether ACPA+ RF+ break through distinct molecular mechanisms.We developed antigen-tetramers isolate performed single-cell RNA sequencing on 2,349 from 6 RA patients 1 healthy donor analyze their immunoglobulin...
Blood and tissue are composed of many functionally distinct cell subsets. In immunological studies, these can be measured accurately only using single-cell assays. The characterization small subsets is crucial to decipher system-level biological changes. For this reason, an increasing number studies rely on assays that provide measurements multiple genes proteins from bulk samples. A common problem in the analysis such data identify biomarkers (or combinations biomarkers) differentially...
Advances in high-throughput, single cell gene expression are allowing interrogation of heterogeneity. However, there is concern that the cycle phase a might bias characterizations at single-cell level. We assess effect on cells by measuring 333 genes 930 across three phases and lines. determine each cell's non-invasively without chemical arrest use it as covariate tests differential expression. observe bi-modal expression, previously-described phenomenon, wherein otherwise abundant either...
The synovial lymphatic system (SLS) removes catabolic factors from the joint. Vascular endothelial growth factor C (VEGF-C) and its receptor, VEGFR-3, are crucial for lymphangiogenesis. However, their involvement in age-related osteoarthritis (OA) is unknown. This study was undertaken to determine whether SLS VEGF-C/VEGFR-3 pathway contribute development progression of OA, using a murine model naturally occurring joint disease.
With white blood cell count emerging as an important risk factor for chronic inflammatory diseases, genetic associations of differential leukocyte types, specifically monocyte count, are providing novel candidate genes and pathways to further investigate. Circulating monocytes play a critical role in vascular diseases such the formation atherosclerotic plaque. We performed joint ancestry-stratified genome-wide association analyses identify variants associated with 11 014 subjects electronic...
Summary Rheumatoid arthritis (RA) is a prototypical autoimmune disease that causes destructive tissue inflammation in joints and elsewhere. Clinical challenges RA include the empirical selection of drugs to treat patients, inadequate responders with incomplete remission, lack cure. We profiled full spectrum cells inflamed synovium from patients goal deconstructing cell states pathways characterizing pathogenic heterogeneity RA. Our multicenter consortium effort used multi-modal CITE-seq,...
Ectopic lymphoid structures (ELS) can develop in rheumatoid arthritis (RA) synovial tissue, but the precise pathways of B cell activation and selection are not well understood. Here, we identify a population characterized by co-expression family orphan nuclear receptors (NR4A1-3), which is highly enriched RA tissue. A transcriptomic profile NR4A cells significantly overlaps with germinal center light zone an accrual somatic hypermutation that correlates loss naive state. co-express...