A5042986766- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Immune cells in cancer
- Cancer-related gene regulation
- RNA Research and Splicing
- Genomics and Rare Diseases
- Protein Degradation and Inhibitors
- RNA and protein synthesis mechanisms
- Gene Regulatory Network Analysis
- Cancer Immunotherapy and Biomarkers
- Signaling Pathways in Disease
- Advanced biosensing and bioanalysis techniques
- Acute Myeloid Leukemia Research
- Bacteriophages and microbial interactions
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomic variations and chromosomal abnormalities
- Nanopore and Nanochannel Transport Studies
- Cell Image Analysis Techniques
- Prenatal Screening and Diagnostics
OHSU Knight Cancer Institute
2021-2025
Oregon Health & Science University
2015-2024
Cardiovascular Institute of the South
2016-2022
University of Portland
2021-2022
Advanced Research Institute
2021
ORCID
2021
Thermo Fisher Scientific (Sweden)
2019-2020
University of Washington
2010-2019
Fred Hutch Cancer Center
2013
Memorial University of Newfoundland
1998
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...
Abstract We characterize and extend a highly efficient method for constructing shotgun fragment libraries in which transposase catalyzes vitro DNA fragmentation adaptor incorporation simultaneously. apply this to sequencing human genome find that coverage biases are comparable those of conventional protocols. also its capabilities by developing protocols sub-nanogram library construction, exome capture from 50 ng input DNA, PCR-free colony PCR 96-plex sample indexing.
Recent years have seen development and implementation of anticancer therapies targeted to particular gene mutations, but methods assay clinical cancer specimens in a comprehensive way for the critical mutations remain underdeveloped. We developed UW-OncoPlex, molecular diagnostic provide simultaneous deep-sequencing information, based on >500× average coverage, all classes 194 clinically relevant genes. To validate we tested 98 previously characterized tumor from 10 different types,...
SARS-CoV-2 and its variants continue to infect hundreds of thousands every day despite the rollout effective vaccines. Therefore, it is essential understand levels protection that these vaccines provide in face emerging variants. Here, we report two demographically balanced cohorts BNT162b2 vaccine recipients COVID-19 patients, from which evaluate neutralizing antibody titers against as well B.1.1.7 (alpha) B.1.351 (beta) We show both are less neutralized by serum vaccinated individuals,...
Abstract Rare-cleaving endonucleases have emerged as important tools for making targeted genome modifications. While multiple platforms are now available to generate reagents research applications, each existing platform has significant limitations in one or more of three key properties necessary therapeutic application: efficiency cleavage at the desired target site, specificity (i.e. rate ‘off-target’ sites), and efficient/facile means delivery cells. Here, we describe development a...
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...
Abstract Intratumoral heterogeneity in cancers arises from genomic instability and epigenomic plasticity is associated with resistance to cytotoxic targeted therapies. We show here that cell-state heterogeneity, defined by differentiation-state marker expression, high triple-negative basal-like breast cancer subtypes, drug tolerant persister (DTP) cell populations altered expression emerge during treatment a wide range of pathway-targeted therapeutic compounds. MEK PI3K/mTOR inhibitor-driven...
We have adapted transposase-based in vitro shotgun library construction (“tagmentation”) for whole-genome bisulfite sequencing. This method, Tn5mC-seq, enables a >100-fold reduction starting material relative to conventional protocols, such that we generate highly complex sequencing libraries from as little 10 ng of input DNA, and ample useful sequences 1 DNA. demonstrate Tn5mC-seq by the methylome human lymphoblastoid cell line ∼8.6× high-quality coverage each strand.
Aneuploidy that arises during meiosis and/or mitosis is a major contributor to early embryo loss. We previously showed human preimplantation embryos encapsulate missegregated chromosomes into micronuclei while undergoing cellular fragmentation and fragments can contain chromosomal material, but the source of this DNA was unknown. Here, we leveraged use nonhuman primate model single-cell DNA-sequencing (scDNA-seq) examine content 471 individual samples comprising 254 blastomeres, 42 polar...
Abstract High-throughput single-cell epigenomic assays can resolve cell type heterogeneity in complex tissues, however, spatial orientation is lost. Here, we present combinatorial indexing on Microbiopsies Assigned to Positions for the Assay Transposase Accessible Chromatin, or sciMAP-ATAC, as a method highly scalable, spatially resolved, profiling of chromatin states. sciMAP-ATAC produces data equivalent quality non-spatial sci-ATAC and retains positional information each within 214 micron...