A5076739142- Single-cell and spatial transcriptomics
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Gene Regulatory Network Analysis
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Gene expression and cancer classification
- Immune Cell Function and Interaction
- Medical Imaging Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Birth, Development, and Health
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- T-cell and B-cell Immunology
- Neurological Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Cancer Genomics and Diagnostics
- Asthma and respiratory diseases
- Pregnancy and preeclampsia studies
- Immunotherapy and Immune Responses
- Genomics and Chromatin Dynamics
- Atherosclerosis and Cardiovascular Diseases
- Cell Image Analysis Techniques
- CRISPR and Genetic Engineering
- Immune cells in cancer
Ajou University
2024-2025
Broad Institute
2017-2024
University of British Columbia
2021-2024
Provincial Health Services Authority
2022-2024
Yale University
2024
Massachusetts Institute of Technology
2017-2023
Samsung Medical Center
2023
Vassar College
2023
Sungkyunkwan University
2023
Thermo Fisher Scientific (Sweden)
2020
The Genotype-Tissue Expression (GTEx) project dissects how genetic variation affects gene expression and splicing.
Cell type composition, estimated from bulk tissue, maps the cellular specificity of genetic variants.
Telomere length within an individual varies in a correlated manner across most tissues.
Abstract Annotating the molecular basis of human disease remains an unsolved challenge, as 93% loci are non-coding and gene-regulatory annotations highly incomplete 1–3 . Here we present EpiMap, a compendium comprising 10,000 epigenomic maps across 800 samples, which used to define chromatin states, high-resolution enhancers, enhancer modules, upstream regulators downstream target genes. We this resource annotate 30,000 genetic that were associated with 540 traits 4 , predicting...
Altered microglial states affect neuroinflammation, neurodegeneration, and disease but remain poorly understood. Here, we report 194,000 single-nucleus transcriptomes epigenomes across 443 human subjects diverse Alzheimer's (AD) pathological phenotypes. We annotate 12 transcriptional states, including AD-dysregulated homeostatic, inflammatory, lipid-processing states. identify 1,542 AD-differentially-expressed genes, both microglia-state-specific disease-stage-specific alterations. By...
Recent work has identified dozens of non-coding loci for Alzheimer's disease (AD) risk, but their mechanisms and AD transcriptional regulatory circuitry are poorly understood. Here, we profile epigenomic transcriptomic landscapes 850,000 nuclei from prefrontal cortexes 92 individuals with without to build a map the brain regulome, including profiles, regulators, co-accessibility modules, peak-to-gene links in cell-type-specific manner. We develop methods multimodal integration detecting...
Article29 November 2018Open Access Transparent process Dynamic control of endogenous metabolism with combinatorial logic circuits Felix Moser Department Biological Engineering, Synthetic Biology Center, Massachusetts Institute Technology, Cambridge, MA, USA Search for more papers by this author Amin Espah Borujeni Amar N. Ghodasara Ewen Cameron Yongjin Park Christopher A. Voigt Corresponding Author [email protected] orcid.org/0000-0003-0844-4776 Information Moser1, Borujeni1, Ghodasara1,...
Article9 November 2017Open Access Transparent process Genetic circuit characterization and debugging using RNA-seq Thomas E Gorochowski orcid.org/0000-0003-1702-786X Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute Technology, Cambridge, MA, USA Search for more papers by this author Amin Espah Borujeni orcid.org/0000-0002-3036-7183 Yongjin Park Alec AK Nielsen Jing Zhang Bryan S Der D Benjamin Gordon Broad MIT Harvard, Christopher A Voigt Corresponding...
This study aimed to establish the optimal cutoff values for visual amyloid positivity using standardized uptake value ratios (SUVRs) in [18F]flutemetamol (FMM) positron emission tomography (PET) imaging. Given variability assessment, our goal was determine that enhance diagnostic accuracy and assist clinicians reliably identifying positivity. The identified were > 1.6 cerebellar gray matter, 1.38 whole cerebellum, 0.63 pons, yielding high sensitivity (95.5%, 94.5%, 95.8%, respectively)...
Immune dysfunctions are believed to contribute bipolar disorder (BD), yet their mechanistic basis remains unclear. To address this, we systematically characterize BD-associated epigenomic and genetic variation in peripheral blood immune cells by profiling integrating 833 genome-wide maps of five histone modification marks across 180 individuals (88 Type I BD patients, 92 controls), coupled with whole-genome sequencing data rich medical records. We annotate 450k candidate cis-regulatory...
Despite recent discoveries in genome-wide association studies (GWAS) of genomic variants associated with Alzheimer's disease (AD), its underlying biological mechanisms are still elusive. The discovery novel AD-associated genetic variants, particularly coding regions and from APOE ε4 non-carriers, is critical for understanding the pathology AD. In this study, we carried out an exome-wide analysis age-of-onset AD ~20,000 subjects placed more emphasis on non-carriers. Using Cox mixed-effects...
Autoimmune diseases, among the most common disorders of young adults, are mediated by genetic and environmental factors. Although CD4 + FOXP3 regulatory T cells (T regs ) play a central role in preventing autoimmunity, molecular mechanism underlying their dysfunction is unknown. Here, we performed comprehensive transcriptomic epigenomic profiling autoimmune disease multiple sclerosis (MS) to identify critical transcriptional programs regulating human autoimmunity. We found that up-regulation...
In multicellular organisms, cell identity and functions are primed refined through interactions with other surrounding cells. Here, we propose a scalable machine learning method, termed SPRUCE, which is designed to systematically ascertain common cell-cell communication patterns embedded in single-cell RNA-seq data. We applied our approach investigate tumor microenvironments consolidating multiple breast cancer datasets found seven frequently observed interaction signatures underlying...
Abstract Thousands of genetic variants acting in multiple cell types underlie complex disorders, yet most gene expression studies profile only bulk tissues, making it hard to resolve where and non-genetic contributors act. This is particularly important for psychiatric neurodegenerative disorders that impact brain with highly-distinct patterns proportions. To address this challenge, we develop a new framework, SPLITR, integrates single-nucleus RNA-seq data, enabling phenotype-aware...
Pulmonary lymphangitic carcinomatosis (PLC) is associated with a poor prognosis in patients non-small cell lung cancer (NSCLC). We sought to determine prognostic value of pretherapeutic fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed (CT) NSCLC radiologically diagnosed PLC. retrospectively reviewed 50 Among eight clinical variables and five imaging parameters, metabolic PLC burden, which represents the overall tumor burden PLC, cPLC, location extent...
Finding a causal gene is fundamental problem in genomic medicine. We present inference framework, CoCoA-diff, that prioritizes disease genes by adjusting confounders without prior knowledge of control variables single-cell RNA-seq data. demonstrate our method substantially improves statistical power simulations and real-world data analysis 70k brain cells collected for dissecting Alzheimer's disease. identify 215 differentially regulated various cell types, including highly relevant with...
Molecular quantitative trait loci (QTLs) allow us to understand the biology captured in genome-wide association studies (GWASs). The placenta regulates fetal development and shows sex differences DNA methylation. We therefore hypothesized that placental methylation QTL (mQTL) explain variation genetic risk for childhood onset traits, effects differ by sex. analyzed 411 term placentas from two found 49,252 (CpG) sites with mQTL 2,489 CpG sex-dependent mQTL. All were enriched regions typically...
Abstract Characterizing the intermediate phenotypes, such as gene expression, that mediate genetic effects on complex diseases is a fundamental problem in human genetics. Existing methods utilize genotypic data and summary statistics to identify putative disease genes, but cannot distinguish pleiotropy from causal mediation are limited by overly strong assumptions about data. To overcome these limitations, we develop Causal Multivariate Mediation within Extended Linkage disequilibrium...
Building a comprehensive topic model has become an important research tool in single-cell genomics. With model, we can decompose and ascertain distinctive cell topics shared across multiple cells, the gene programs implicated by each later serve as predictive translational studies. Here, present Bayesian that uncover short-term RNA velocity patterns from plethora of spliced unspliced RNA-sequencing (RNA-seq) counts. We showed modeling both types counts improve robustness statistical...
Abstract Cerebrovascular breakdown occurs early in Alzheimer’s Disease (AD), but its cell-type-specific molecular basis remains uncharacterized. Here, we characterize single-cell transcriptomic differences human cerebrovasculature across 220 AD and 208 control individuals 6 brain regions. We annotate 22,514 cerebrovascular cells 11 subtypes of endothelial, pericyte, smooth muscle, perivascular fibroblast, ependymal cells, how they differ abundance gene expression between identify 2,676...
Abstract Despite significant advances in identifying genetic drivers of neurodegenerative disorders, the majority affected individuals lack molecular diagnosis, with somatic mutations proposed as one potential contributor to increased risk. Here, we report first cell-type-specific map mosaicism Alzheimer’s Dementia (AlzD), using 4,014 cells from prefrontal cortex samples 19 AlzD and 17 non-AlzD individuals. We integrate full-transcript single-nucleus RNA-seq (SMART-Seq) matched...