A5068022850- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Genetics, Aging, and Longevity in Model Organisms
- Advanced biosensing and bioanalysis techniques
- Gene Regulatory Network Analysis
- Genomics and Rare Diseases
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- Muscle Physiology and Disorders
- Retinal Development and Disorders
- Cancer Genomics and Diagnostics
- Zebrafish Biomedical Research Applications
- RNA modifications and cancer
- Migration and Labor Dynamics
- Liver Disease Diagnosis and Treatment
- Bioinformatics and Genomic Networks
- Electron Spin Resonance Studies
- Pluripotent Stem Cells Research
- Endoplasmic Reticulum Stress and Disease
- Physiological and biochemical adaptations
- Diet, Metabolism, and Disease
- Congenital heart defects research
- Cell Image Analysis Techniques
- Genetic Associations and Epidemiology
Foresite (United States)
2021-2025
University of Washington
2017-2023
Seattle University
2019
Regeneron (United States)
2015-2018
Human Genome Sciences (United States)
2018
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....
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...
Elucidation of the genetic factors underlying chronic liver disease may reveal new therapeutic targets.
The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System couples high-throughput sequencing to an integrated health care system using longitudinal electronic records (EHRs). We sequenced exomes of 50,726 adult participants in study identify ~4.2 million rare single-nucleotide variants insertion/deletion events, which ~176,000 are predicted result a loss gene function. Linking these data EHR-derived clinical phenotypes, we find associations supporting...
Identifying terminal nematode cells Single-cell RNA sequencing provides the power to identify developmental trajectory of an organism. However, identifying temporal lineage cell development can be difficult without large-scale analyses. Packer et al. sequenced more than 80,000 from embryos roundworm Caenorhabditis elegans determine expression genes directing types. Because all somatic in a C. individual have been mapped, authors are able connect gene with lineages over time during...
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...
Spatial patterns of gene expression manifest at scales ranging from local (e.g., cell-cell interactions) to global body axis patterning). However, current spatial transcriptomics methods either average contexts or are restricted limited fields view. Here, we introduce sci-Space, which retains single-cell resolution while resolving heterogeneity larger scales. Applying sci-Space developing mouse embryos, captured approximate coordinates and whole transcriptomes about 120,000 nuclei. We...
Thyroid hormone (TH) regulates diverse developmental events and can drive disparate cellular outcomes. In zebrafish, TH has opposite effects on neural crest derived pigment cells of the adult stripe pattern, limiting melanophore population expansion, yet increasing yellow/orange xanthophore numbers. To learn how elicits seemingly responses in having a common embryological origin, we analyzed individual transcriptomes from thousands crest-derived cells, reconstructed trajectories, identified...
Abstract Motivation: Several algorithms exist for detecting copy number variants (CNVs) from human exome sequencing read depth, but previous tools have not been well suited large population studies on the order of tens or hundreds thousands exomes. Their limitations include being difficult to integrate into automated variant-calling pipelines and ill-suited common variants. To address these issues, we developed a new algorithm—Copy estimation using Lattice-Aligned Mixture Models...
Abstract Conventional methods for profiling the molecular content of biological samples fail to resolve heterogeneity that is present at level single cells. In past few years, cell RNA sequencing has emerged as a powerful strategy overcoming this challenge. However, its adoption been limited by paucity are once simple implement and cost effective scale massively. Here, we describe combinatorial indexing profile transcriptomes large numbers cells or nuclei without requiring physical isolation...
Abstract C. elegans is an animal with few cells, but a striking diversity of cell types. Here, we characterize the molecular basis for their specification by profiling transcriptomes 84,625 single embryonic cells. We identify 284 terminal and pre-terminal types, mapping most to exact position in elegans’ invariant lineage. use these annotations perform first quantitative analysis relationship between lineage transcriptome whole organism. find that strong lineage-transcriptome correlation...
Abstract Over a million DNA regulatory elements have been cataloged in the human genome, but linking these to genes that they regulate remains challenging. We introduce Cicero, statistical method connects target using single cell chromatin accessibility data. apply Cicero investigate how thousands of dynamically accessible orchestrate gene regulation differentiating myoblasts. Groups co-accessible linked by meet criteria “chromatin hubs”, are physically proximal, interact with common set...
Abstract Copy number variants (CNVs) are a substantial source of genomic variation and contribute to wide range human disorders. Gene-disrupting exonic CNVs have important clinical implications as they can underlie variability in disease presentation susceptibility. The relationship between traits has not been broadly explored at the population level, primarily due technical challenges. We surveyed common rare exome sequences 50,726 adult DiscovEHR study participants with linked electronic...
Mutations in the DMD gene lead to Duchenne muscular dystrophy (DMD), a severe neuromuscular disorder affecting young boys as they acquire motor functions. is typically diagnosed at 2-4 years of age, but absence dystrophin has negative impacts on skeletal muscles before overt symptoms appear patients, which poses serious challenge current standards care. Here, we investigated consequences deficiency during muscle development. We used single-cell transcriptome profiling characterize myogenic...
Circulating endocrine factors are critical for orchestrating complex developmental processes during the generation of adult form. One such factor, thyroid hormone, regulates diverse cellular post-embryonic development and can drive disparate morphological outcomes through mechanisms that remain essentially unknown. We sought to define how hormone elicits opposite responses in abundance two pigment cell classes zebrafish pattern. By profiling individual transcriptomes from thousands neural...
Summary Mutations in the DMD gene lead to Duchenne muscular dystrophy, a severe X-linked neuromuscular disorder that manifests itself as young boys acquire motor functions. is typically diagnosed at 2 4 years of age, but absence dystrophin negatively impacts muscle structure and function before overt symptoms appear patients, which poses serious challenge optimization standards care. In this report, we investigated early consequences deficiency during skeletal development. We used...
Abstract Several groups recently reported coupling CRISPR/Cas9 perturbations and single cell RNA-seq as a potentially powerful approach for forward genetics. Here we demonstrate that vector designs such screens rely on cis linkage of guides distally located barcodes suffer from swapping intended guide-barcode associations at rates approaching 50% due to template switching during lentivirus production, greatly reducing sensitivity. We optimize published strategy, CROP-seq, instead uses Pol II...