A5069196767- Helicobacter pylori-related gastroenterology studies
- Eosinophilic Esophagitis
- Single-cell and spatial transcriptomics
- IL-33, ST2, and ILC Pathways
- Gene expression and cancer classification
- Galectins and Cancer Biology
- Cell Image Analysis Techniques
- Mycobacterium research and diagnosis
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Gastric Cancer Management and Outcomes
- HIV Research and Treatment
- Gastrointestinal disorders and treatments
- Gene Regulatory Network Analysis
- Scientific Computing and Data Management
- Cancer Cells and Metastasis
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- Molecular Biology Techniques and Applications
- vaccines and immunoinformatics approaches
- Digestive system and related health
- Research Data Management Practices
- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Immunodeficiency and Autoimmune Disorders
Fred Hutch Cancer Center
2015-2024
Harvard University
2024
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2012-2022
Cancer Research Center
2014-2022
Infectious Disease Research Institute
2019-2021
Cancer Research And Biostatistics
2019
Centre for Cancer Biology
2018
BC Cancer Agency
2014-2016
University of British Columbia
2014-2016
Baxter (United States)
2015-2016
Single-cell transcriptomics reveals gene expression heterogeneity but suffers from stochastic dropout and characteristic bimodal distributions in which is either strongly non-zero or non-detectable. We propose a two-part, generalized linear model for such data that parameterizes both of these features. argue the cellular detection rate, fraction genes expressed cell, should be adjusted as source nuisance variation. Our provides set enrichment analysis tailored to single-cell data. It...
In this analysis, the authors directly compared performance of flow cytometry data processing algorithms to manual gating approaches. The results offer information practical utility about as applied different sets and challenges. Traditional methods for (FCM) rely on subjective gating. Recently, several groups have developed computational identifying cell populations in multidimensional FCM data. Flow Cytometry: Critical Assessment Population Identification Methods (FlowCAP) challenges were...
Abstract Motivation: Cell populations are never truly homogeneous; individual cells exist in biochemical states that define functional differences between them. New technology based on microfluidic arrays combined with multiplexed quantitative polymerase chain reactions now enables high-throughput single-cell gene expression measurement, allowing assessment of cellular heterogeneity. However, few analytic tools have been developed specifically for the statistical and analytical challenges...
Abstract Standardization of immunophenotyping requires careful attention to reagents, sample handling, instrument setup, and data analysis, is essential for successful cross-study cross-center comparison data. Experts developed five standardized, eight-color panels identification major immune cell subsets in peripheral blood. These were produced as pre-configured, lyophilized, reagents 96-well plates. We present the results a coordinated analysis samples across nine laboratories using these...
Flow cytometry is used increasingly in clinical research for cancer, immunology and vaccines. Technological advances instrumentation are increasing the size dimensionality of data sets, posing a challenge traditional management analysis. Automated analysis methods, despite general consensus their importance to future field, have been slow gain widespread adoption. Here we present OpenCyto, new BioConductor infrastructure framework designed lower barrier entry automated flow algorithms by...
Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01
Caveolin-1 (CAV1) is an essential structural constituent of caveolae, specialized lipid raft microdomains on the cell membrane involved in endocytosis and signal transduction, which are inexplicably deregulated associated with aggressiveness numerous cancers. Here we identify CAV1 as a direct transcriptional target oxygen-labile hypoxia-inducible factor 1 2 that accentuates formation leading to increased dimerization EGF receptor within confined surface area caveolae its subsequent...
Conventional memory CD8+ T cells and mucosal-associated invariant (MAIT cells) are found in blood, liver, mucosal tissues have similar effector potential following activation, specifically expression of IFN-γ granzyme B. To better understand each subset's unique contributions to immunity pathology, we interrogated inflammation- TCR-driven activation requirements using human MAIT isolated from blood tissue biopsies ex vivo functional assays single cell gene experiments. We that had a robust B...
Summary: flowDensity facilitates reproducible, high-throughput analysis of flow cytometry data by automating a predefined manual gating approach. The algorithm is based on sequential bivariate approach that generates set cell populations. It chooses the best cut-off for individual markers using characteristics density distribution. Supplementary Data linked to online version manuscript. Availability and implementation: R source code freely available through BioConductor...
The engineered outer domain germline targeting version 8 (eOD-GT8) 60-mer nanoparticle was designed to prime VRC01-class HIV-specific B cells that would need be matured, through additional heterologous immunizations, into are able produce broadly neutralizing antibodies. CD4 T cell help will critical for the development of such high-affinity antibody responses. Thus, we assessed induction and epitope specificities vaccine-specific from IAVI G001 phase 1 clinical trial tested immunization...
Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise development of precision vaccines against major human pathogens. In a clinical trial the eOD-GT8 60mer germline-targeting immunogen, higher frequencies vaccine-induced VRC01-class bnAb-precursor B cells were observed in high dose compared to low group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification IGHV1-2 allele usage and...
Abstract Introduction The role of the cellular microenvironment in breast tumorigenesis has become an important research area. However, little is known about gene expression histologically normal tissue adjacent to tumor, if this influenced by and how compares with non-tumor-bearing tissue. Methods To address this, we have generated profiles morphologically epithelial stromal tissue, isolated using laser capture microdissection, from patients cancer or undergoing reduction mammoplasty ( n =...
We present a framework for the identification of cell subpopulations in flow cytometry data based on merging mixture components using flowClust methodology. show that cluster algorithm under our improves model fit and provides better estimate number distinct than either Gaussian models or flowClust, especially complicated distributions. Our allows automated selection we are able to identify cases where fails, thus making it suitable application high throughput FCM analysis pipeline....
In a high throughput setting, effective flow cytometry data analysis depends heavily on proper preprocessing. While usual preprocessing steps of quality assessment, outlier removal, normalization, and gating have received considerable scrutiny from the community, influence transformation output has been largely overlooked. Flow measurements can vary over several orders magnitude, cell populations variances that depend their mean fluorescence intensities, may exhibit heavily-skewed...
Open source software for computational cytometry has gained in popularity over the past few years. Efforts such as FlowCAP, Lyoplate and Euroflow projects have highlighted importance of efforts to standardize both experimental aspects data analysis. The R/BioConductor platform hosts largest collection open covering all analysis providing infrastructure represent analyze with relevant experimental, gating cell population annotations enabling fully reproducible Data visualization frameworks...
Blood and tissue are composed of many functionally distinct cell subsets. In immunological studies, these can be measured accurately only using single-cell assays. The characterization small subsets is crucial to decipher system-level biological changes. For this reason, an increasing number studies rely on assays that provide measurements multiple genes proteins from bulk samples. A common problem in the analysis such data identify biomarkers (or combinations biomarkers) differentially...
Advances in high-throughput, single cell gene expression are allowing interrogation of heterogeneity. However, there is concern that the cycle phase a might bias characterizations at single-cell level. We assess effect on cells by measuring 333 genes 930 across three phases and lines. determine each cell's non-invasively without chemical arrest use it as covariate tests differential expression. observe bi-modal expression, previously-described phenomenon, wherein otherwise abundant either...
The Flow Cytometry: Critical Assessment of Population Identification Methods (FlowCAP) challenges were established to compare the performance computational methods for identifying cell populations in multidimensional flow cytometry data. Here we report results FlowCAP-IV where algorithms from seven different research groups predicted time progression AIDS among a cohort 384 HIV+ subjects, using antigen-stimulated peripheral blood mononuclear (PBMC) samples analyzed with 14-color staining...
It is important to identify vaccine-induced immune responses that predict the preventative efficacy of a human immunodeficiency virus (HIV)-1 vaccine. We assessed T-cell response markers as correlates risk in HIV Vaccine Trials Network (HVTN) 505 HIV-1 vaccine trial.2504 participants were randomized DNA/rAd5 or placebo, administered at weeks 0, 4, 8, and 24. Peripheral blood mononuclear cells obtained week 26 from all 25 primary endpoint cases 125 matched controls, stimulated with...