A5069366529- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Pancreatic and Hepatic Oncology Research
- Cell Image Analysis Techniques
- Gene expression and cancer classification
- Gene Regulatory Network Analysis
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Caveolin-1 and cellular processes
- Retinal Development and Disorders
- Neurogenesis and neuroplasticity mechanisms
- Cancer Cells and Metastasis
- Neuroinflammation and Neurodegeneration Mechanisms
- Pluripotent Stem Cells Research
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- AI in cancer detection
- Immune cells in cancer
- Genetics, Bioinformatics, and Biomedical Research
- Molecular Biology Techniques and Applications
Johns Hopkins University
2016-2025
Johns Hopkins Medicine
2015-2025
Discovery Institute
2020-2025
Sidney Kimmel Comprehensive Cancer Center
2016-2024
Convergence
2021-2024
University of Baltimore
2017-2024
St.Petersburg V.M.Bekhterev Psychoneurological Research Institute
2021-2024
Bloomberg (United States)
2021-2024
Lieber Institute for Brain Development
2015-2024
Hospital for Sick Children
2024
Analysis of gene expression in single cells allows for decomposition cellular states as low-dimensional latent spaces. However, the interpretation and validation these spaces remains a challenge. Here, we present scCoGAPS, which defines from source single-cell RNA-sequencing (scRNA-seq) dataset, projectR, evaluates independent target datasets via transfer learning. Application developing mouse retina to scRNA-Seq reveals intrinsic relationships across biological contexts assays while...
Abstract Psychedelics are a broad class of drugs defined by their ability to induce an altered state consciousness 1,2 . These have been used for millennia in both spiritual and medicinal contexts, number recent clinical successes spurred renewed interest developing psychedelic therapies 3–9 Nevertheless, unifying mechanism that can account these shared phenomenological therapeutic properties remains unknown. Here we demonstrate mice the reopen social reward learning critical period is...
Cancer is a complex disease, driven by aberrant activity in numerous signaling pathways even individual malignant cells. Epigenetic changes are critical mediators of these functional that drive and maintain the phenotype. Changes DNA methylation, histone acetylation noncoding RNAs, posttranslational modifications all epigenetic drivers cancer, independent sequence. These alterations were once thought to be crucial only for phenotype maintenance. Now, also recognized as disrupting essential...
Abstract Background The cell cycle is a highly conserved, continuous process which controls faithful replication and division of cells. Single-cell technologies have enabled increasingly precise measurements the both as biological interest possible confounding factor. Despite its importance conservation, there no universally applicable approach to infer position in with high-resolution from single-cell RNA-seq data. Results Here, we present tricycle, an R/Bioconductor package, address this...
RNA velocity analysis of single cells offers the potential to predict temporal dynamics from gene expression. In many systems, has been observed produce a vector field that qualitatively reflects known features system. However, limitations estimates are still not well understood.
Background: Clinical trials of anti-Aβ monoclonal antibodies in Alzheimer disease (AD) infer target engagement from Aβ positron emission tomography (PET) and/or fluid biomarkers such as cerebrospinal (CSF) Aβ42/40.However, these measure deposits indirectly incompletely.In contrast, postmortem neuropathologic assessments allow direct investigation treatment effects on brain and many other pathologic features.Methods: From a clinical trial dominantly inherited AD, we measured...
Abstract Motivation Dimension reduction techniques are widely used to interpret high-dimensional biological data. Features learned from these methods discover both technical artifacts and novel phenomena. Such feature discovery is critically importent in analysis of large single-cell datasets, where lack a ground truth limits validation interpretation. Transfer learning (TL) can be relate the features one source dataset new target perform biologically driven by evaluating their use or...
Autoimmune uveoretinitis is a significant cause of visual loss, and mouse models offer unique opportunities to study its disease mechanisms. Aire-/- mice fail express self-antigens in the thymus, exhibit reduced central tolerance, develop spontaneous, chronic, progressive uveoretinitis. Using single-cell RNA sequencing (scRNA-seq), we characterized wild-type retinas define, comprehensive unbiased manner, cell populations gene expression patterns associated with disease. Based on scRNA-seq,...
The mammalian CNS is capable of tolerating chronic hypoxia, but cell type-specific responses to this stress have not been systematically characterized. In the Norrin KO ( Ndp ) mouse, a model familial exudative vitreoretinopathy (FEVR), developmental hypovascularization retina produces hypoxia inner nuclear-layer (INL) neurons and Muller glia. We used single-cell RNA sequencing, untargeted metabolomics, metabolite labeling from 13 C-glucose compare WT retinas. retinas, we observe gene...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify cell and CAF interactions through the integration of single-cell data from human tumors organoid coculture experiments. Analysis comprehensive atlas PDAC RNA sequencing indicated that density associated increased inflammation epithelial–mesenchymal transition...
Non-negative Matrix Factorization (NMF) algorithms associate gene expression with biological processes (e.g. time-course dynamics or disease subtypes). Compared univariate associations, the relative weights of NMF solutions can obscure biomarkers. Therefore, we developed a novel patternMarkers statistic to extract genes for validation and enhanced visualization results. Finding unbiased markers requires whole-genome data. also Genome-Wide CoGAPS Analysis in Parallel Sets (GWCoGAPS), first...
Abstract Background The majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed at the metastatic stage, and standard therapies have limited activity with a dismal 5-year survival rate only 8%. liver lung most common sites PDAC metastasis, each been differentially associated prognoses responses to systemic therapies. A deeper understanding molecular cellular landscape within tumor microenvironment (TME) metastasis these different is critical informing future therapeutic strategies...
Better understanding of the progression neural stem cells (NSCs) in developing cerebral cortex is important for modeling neurogenesis and defining pathogenesis neuropsychiatric disorders. Here, we use RNA sequencing, cell imaging, lineage tracing mouse human vitro NSCs monkey brain sections to model generation cortical neuronal fates. We show that conserved signaling mechanisms regulate acute transition from proliferative committed glutamatergic excitatory neurons. As telencephalic develop...
Single-cell transcriptomics technologies can uncover changes in the molecular states that underlie cellular phenotypes. However, understanding dynamic processes requires extending from inferring trajectories snapshots of to estimating temporal gene expression. To address this challenge, we have developed a neural ordinary differential-equation-based method, RNAForecaster, for predicting expression single cells multiple future time steps an embedding-independent manner. We demonstrate...
Variability between human pluripotent stem cell (hPSC) lines remains a challenge and opportunity in biomedicine. In this study, hPSC from multiple donors were differentiated toward neuroectoderm mesendoderm lineages. We revealed dynamic transcriptomic patterns that delineate the emergence of these lineages, which conserved across lines, along with individual line-specific transcriptional signatures invariant throughout differentiation. These predicted an antagonism SOX21-driven forebrain...