Aparna Nathan
A5067506805- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immune cells in cancer
- Cytokine Signaling Pathways and Interactions
- COVID-19 Clinical Research Studies
- Genetic Associations and Epidemiology
- Gene expression and cancer classification
- Cell Image Analysis Techniques
- CAR-T cell therapy research
- Tuberculosis Research and Epidemiology
- Bioinformatics and Genomic Networks
- interferon and immune responses
- Systemic Lupus Erythematosus Research
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Renal Diseases and Glomerulopathies
- Molecular Biology Techniques and Applications
- Lymphoma Diagnosis and Treatment
- Genetic Neurodegenerative Diseases
- Dermatology and Skin Diseases
- Gene Regulatory Network Analysis
- CRISPR and Genetic Engineering
- Inflammasome and immune disorders
- Asthma and respiratory diseases
Brigham and Women's Hospital
2018-2025
Harvard University
2018-2025
Broad Institute
2019-2024
Center for Rheumatology
2023
United States Department of Health and Human Services
2021
University of Massachusetts Boston
2021
National Institute of Mental Health
2021
Massachusetts Institute of Technology
1995-2020
Massachusetts General Hospital
2020
Yale University
2015-2018
Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource adult brain across 1866 individuals. The contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles many cell types; quantitative-trait loci (QTLs); further QTLs associated with chromatin, splicing, cell-type...
Abstract Background Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 other inflammatory diseases established therapies help nominate immunomodulatory therapies. Methods To identify cellular phenotypes that be across tissues affected by disparate diseases, we developed meta-analysis integration pipeline models removes effects of technology, tissue origin, donor confound cell-type...
Abstract Recent advances in single-cell technologies and integration algorithms make it possible to construct comprehensive reference atlases encompassing many donors, studies, disease states, sequencing platforms. Much like mapping reads a genome, is essential be able map query cells onto complex, multimillion-cell rapidly identify relevant cell states phenotypes. We present Symphony ( https://github.com/immunogenomics/symphony ), an algorithm for building large-scale, integrated...
Abstract How innate T cells (ITC), including invariant natural killer (iNKT) cells, mucosal-associated (MAIT) and γδ maintain a poised effector state has been unclear. Here we address this question using low-input single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover continuous ‘innateness gradient’, with adaptive at one end, followed by MAIT, iNKT, the other end. Single-cell reveals four broad states innateness, heterogeneity within canonical...
Abstract Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction 1 . There currently no cure for rheumatoid arthritis, the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity 1,2 Here, to deconstruct cell states pathways characterize this heterogeneity, we profiled full spectrum cells in inflamed synovium from patients with arthritis. We used multi-modal single-cell RNA-sequencing surface protein...
Abstract The morphology of cells is dynamic and mediated by genetic environmental factors. Characterizing how variation impacts cell can provide an important link between disease association cellular function. Here, we combine genomic sequencing high-content imaging approaches on iPSCs from 297 unique donors to investigate the relationship variants map what term morphological quantitative trait loci (cmQTLs). We identify novel associations rare protein altering in WASF2 , TSPAN15 PRLR with...
Abstract Summary The related Wilcoxon rank sum test and area under the receiver operator curve are ubiquitous in high dimensional biological data analysis. Current implementations do not scale readily to increasingly large datasets generated by novel high-throughput technologies, such as single cell RNAseq. We introduce a simple scalable implementation of both analyses, available through R package Presto. Presto scales big datasets, with functions optimized for dense sparse matrices. On...
Connectivity webs mediate the unique biology of mammalian brain. Yet, while cell circuit maps are increasingly available, knowledge their underlying molecular networks remains limited. Here, we applied multi-dimensional biochemical fractionation with mass spectrometry and machine learning to survey endogenous macromolecules across adult mouse We defined a global "interactome" comprising over one thousand multi-protein complexes. These include hundreds brain-selective assemblies that have...
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,...
Despite strong evidence of heritability and growing discovery genetic markers for major mental illness, little is known about how gene expression in the brain differs across psychiatric diagnoses, or risk factors shape these differences. Here we investigate expressed genes transcripts postmortem subgenual anterior cingulate cortex (sgACC), a key component limbic circuits linked to illness. RNA obtained from 200 donors diagnosed with bipolar disorder, schizophrenia, depression, no disorder...
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,...
Abstract T-cells recognize antigens and induce specialized gene expression programs (GEPs) enabling functions including proliferation, cytotoxicity, cytokine production. Traditionally, different classes of helper express mutually exclusive responses – for example, Th1, Th2, Th17 programs. However, new single-cell RNA sequencing (scRNA-Seq) experiments have revealed a continuum T-cell states without discrete clusters corresponding to these subsets, implying the need analytical frameworks....
Abstract Granzymes are a family of serine proteases mainly expressed by CD8 + T cells, natural killer and innate-like lymphocytes 1,2 . Although their major role is thought to be the induction cell death in virally infected tumor accumulating evidence suggests some granzymes can regulate inflammation acting on extracellular substrates 2 Recently, we found that majority tissue cells rheumatoid arthritis (RA) synovium, inflammatory bowel disease other inflamed organs express granzyme K (GZMK)...