A5042585562- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Nuclear Structure and Function
- CRISPR and Genetic Engineering
- Ferroptosis and cancer prognosis
- Cancer Cells and Metastasis
- Chemical Reactions and Isotopes
- Drug Transport and Resistance Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Scientific Computing and Data Management
- Metabolism, Diabetes, and Cancer
Broad Institute
2020-2025
Harvard University
2019-2025
Massachusetts Institute of Technology
2025
University of California, San Diego
2015-2019
Understanding genome organization requires integration of DNA sequence and three-dimensional spatial context; however, existing genome-wide methods lack either base pair resolution or direct localization. Here, we describe in situ sequencing (IGS), a method for simultaneously imaging genomes within intact biological samples. We applied IGS to human fibroblasts early mouse embryos, spatially localizing thousands genomic loci individual nuclei. Using these data, characterized parent-specific...
Abstract ATAC-seq is a widely-applied assay used to measure genome-wide chromatin accessibility; however, its ability detect active regulatory regions can depend on the depth of sequencing coverage and signal-to-noise ratio. Here we introduce AtacWorks, deep learning toolkit denoise identify peaks at base-pair resolution from low cell count, low-coverage, or low-quality data. Models trained by AtacWorks types not seen in training data, are generalizable across diverse sample preparations...
Microscopy and genomics are both used to characterize cell function, but approaches connect the two types of information lacking, particularly at subnuclear resolution. While emerging multiplexed imaging methods can simultaneously localize genomic regions nuclear proteins, their ability accurately measure DNA-protein interactions is constrained by diffraction limit optical microscopy. Here, we describe expansion in situ genome sequencing (ExIGS), a technology that enables DNA superresolution...
Summary Cell differentiation and function are regulated across multiple layers of gene regulation, including the modulation expression by changes in chromatin accessibility. However, is an asynchronous process precluding a temporal understanding regulatory events leading to cell fate commitment. Here, we developed SHARE-seq, highly scalable approach for measurement accessibility within same single cell. Using 34,774 joint profiles from mouse skin, develop computational strategy identify cis-...
Spatial epigenomics and multiomics can provide fine-grained insights into cellular states but their widespread adoption is limited by the requirement for bespoke slides capture chemistries each data modality. Here, we present SPatial assay Accessible chromatin, Cell lineages, gene Expression with sequencing (SPACE-seq), a method that utilizes polyadenine-tailed epigenomic libraries to enable facile spatial using standard whole transcriptome reagents. Applying SPACE-seq human glioblastoma...
Abstract We introduce AtacWorks ( https://github.com/clara-genomics/AtacWorks ), a method to denoise and identify accessible chromatin regions from low-coverage or low-quality ATAC-seq data. uses deep neural network learn mapping between noisy data corresponding higher-coverage higher-quality To demonstrate the utility of AtacWorks, we train model on four human blood cell types show that this accurately denoises accessibility at base-pair resolution identifies peaks bulk sequencing unseen...
Transport systems comprise roughly 10% of all proteins in a cell, playing critical roles many processes. Improving and expanding their classification is an important goal that can affect studies ranging from comparative genomics to potential drug target searches. It not surprising different for transport have arisen, be it within specialized database, focused on this functional class proteins, or as part broader system proteins. Two such databases are the Transporter Classification Database...
Abstract A hallmark of cancer development is the loss cellular identity due to dysregulation regulatory networks that maintain functional, differentiated states. Chromatin state has been linked this control and developmental processes; however, mechanisms by which these landscapes are disrupted during progression not well understood. To end, we leveraged an optimized single-cell ATAC-sequencing (scATAC-seq) strategy using a combinatorial indexing-based technology assess chromatin changes...