A5036731592- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Congenital heart defects research
- Pluripotent Stem Cells Research
- Chromosomal and Genetic Variations
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Advanced biosensing and bioanalysis techniques
- Gene Regulatory Network Analysis
- RNA modifications and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Cell Image Analysis Techniques
- Bacteriophages and microbial interactions
- Genomics and Rare Diseases
- T-cell and B-cell Immunology
- Gene expression and cancer classification
- Immune Cell Function and Interaction
- Nanopore and Nanochannel Transport Studies
- MicroRNA in disease regulation
- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Renal and related cancers
University of Washington
2016-2025
Broad Institute
2010-2016
Massachusetts Institute of Technology
2011
Fred Hutch Cancer Center
2002
Czech Academy of Sciences, Institute of Microbiology
2001
Massively parallel DNA sequencing technologies are revolutionizing genomics by making it possible to generate billions of relatively short (~100-base) sequence reads at very low cost. Whereas such data can be readily used for a wide range biomedical applications, has proven difficult use them high-quality de novo genome assemblies large, repeat-rich vertebrate genomes. To date, the generated from have fallen far those obtained with older (but much more expensive) capillary-based approach....
Sequencing each cell of the nematode Single-cell sequencing is challenging owing to limited biological material available in an individual and high cost across multiple cells. Cao et al. developed a two-step combinatorial barcoding method profile both single-cell single-nucleus transcriptomes without requiring physical isolation cell. The authors profiled almost 50,000 single cells from Caenorhabditis elegans larval stage were able identify recover information different, even rare, types....
Chromatin state and the single cell Identifying chromatin of any cell, which may or not have a different function represent stages relative to others collected within culture, experiment, tissue, has been challenging. Cusanovitch et al. skirted previously identified technological limitations identify regions accessible at single-cell resolution. Combinatorial cellular indexing, strategy for multiplex barcoding thousands cells per was successfully used investigate genome-wide accessibility...
Although we can increasingly measure transcription, chromatin, methylation, and other aspects of molecular biology at single-cell resolution, most assays survey only one aspect cellular biology. Here describe sci-CAR, a combinatorial indexing-based coassay that jointly profiles chromatin accessibility mRNA (CAR) in each thousands single cells. As proof concept, apply sci-CAR to 4825 cells, including time series dexamethasone treatment, as well 11,296 cells from the adult mouse kidney. With...
The genomics of human development Understanding the trajectory a developing requires an understanding how genes are regulated and expressed. Two papers now present pooled approach using three levels combinatorial indexing to examine single-cell gene expression chromatin landscapes from 15 organs in fetal samples. Cao et al. focus on measurements RNA broadly distributed cell types provide insights into organ specificity. Domcke examined accessibility cells these identify regulatory elements...
Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor (ctDNA) may afford opportunity to diagnose, monitor recurrence, and evaluate response therapy solely through a non-invasive blood draw. However, detecting ctDNA against normally occurring background cell-free derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences fragment length size between ctDNAs normal are defined. Human...
The genomics of human development Understanding the trajectory a developing requires an understanding how genes are regulated and expressed. Two papers now present pooled approach using three levels combinatorial indexing to examine single-cell gene expression chromatin landscapes from 15 organs in fetal samples. Cao et al. focus on measurements RNA broadly distributed cell types provide insights into organ specificity. Domcke examined accessibility cells these identify regulatory elements...
High-throughput chemical screens typically use coarse assays such as cell survival, limiting what can be learned about mechanisms of action, off-target effects, and heterogeneous responses. Here, we introduce "sci-Plex," which uses "nuclear hashing" to quantify global transcriptional responses thousands independent perturbations at single-cell resolution. As a proof concept, applied sci-Plex screen three cancer lines exposed 188 compounds. In total, profiled ~650,000 transcriptomes across...
Abstract The human embryo undergoes morphogenetic transformations following implantation into the uterus, but our knowledge of this crucial stage is limited by inability to observe in vivo. Models derived from stem cells are important tools for interrogating developmental events and tissue–tissue crosstalk during these stages 1 . Here we establish a model post-implantation embryo, embryoid, comprising embryonic extraembryonic tissues. We combine two types extraembryonic-like cell generated...
Abstract Recent advances in multiplexed single‐cell transcriptomics experiments facilitate the high‐throughput study of drug and genetic perturbations. However, an exhaustive exploration combinatorial perturbation space is experimentally unfeasible. Therefore, computational methods are needed to predict, interpret, prioritize Here, we present compositional autoencoder (CPA), which combines interpretability linear models with flexibility deep‐learning approaches for response modeling. CPA...
Abstract DNA is naturally well suited to serve as a digital medium for in vivo molecular recording. However, contemporary DNA-based memory devices are constrained terms of the number distinct ‘symbols’ that can be concurrently recorded and/or by failure capture order which events occur 1 . Here we describe Typewriter, general system recording overcomes these and other limitations. For blank (‘DNA Tape’) consists tandem array partial CRISPR–Cas9 target sites, with all but first site truncated...
Drosophila melanogaster is a powerful, long-standing model for metazoan development and gene regulation. We profiled chromatin accessibility in almost 1 million expression half nuclei from overlapping windows spanning the entirety of embryogenesis. Leveraging developmental asynchronicity within embryo collections, we applied deep neural networks to infer age each nucleus, resulting continuous, multimodal views molecular cellular transitions absolute time. identify cell lineages; their...
Abstract The house mouse ( Mus musculus ) is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans 1,2 . Mouse gestation lasts only 3 weeks, during which the genome orchestrates astonishing transformation of a single-cell zygote into free-living pup composed more than 500 million cells. Here, establish global framework for exploring mammalian development, we applied optimized combinatorial indexing profile transcriptional states 12.4 nuclei...
We set out to exhaustively characterize the impact of cis-chromatin environment on prime editing, a precise genome engineering tool. Using highly sensitive method for mapping genomic locations randomly integrated reporters, we discover massive position effects, exemplified by editing efficiencies ranging from ∼0% 94% an identical target site and edit. Position effects efficiency are well predicted chromatin marks, e.g., positively H3K79me2 negatively H3K9me3. Next, developed multiplex...
The immune system encodes information about the severity of a pathogenic threat in quantity and type memory cells it forms. This encoding emerges from lymphocyte decisions to maintain or lose self-renewal potential during challenge. By tracking CD8+ T at single-cell clonal lineage level using time-resolved transcriptomics, quantitative live imaging, an acute infection model, we find that will early after antigen recognition. However, following pathogen clearance, may regain if initially...
We describe a method that exploits c ontiguity p reserving t ransposase seq uencing (CPT-seq) to facilitate the scaffolding of de novo genome assemblies. CPT-seq is an entirely in vitro means generating libraries comprised 9216 indexed pools, each which contains thousands sparsely sequenced long fragments ranging from 5 kilobases >1 megabase. These pools are “subhaploid,” lengths contained pool sums ∼5% 10% full genome. The approach described here, termed fragScaff , leverages...
The germline genome of the binucleated ciliate Tetrahymena thermophila undergoes programmed chromosome breakage and massive DNA elimination to generate somatic genome. Here, we present a complete sequence assembly analyze multiple features its structure relationship genome, shedding light on mechanisms rearrangement as well evolutionary history this remarkable germline/soma differentiation. Our results strengthen notion that complex, dynamic, ongoing interplay between mobile elements host...