A5005741024- Helicobacter pylori-related gastroenterology studies
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Eosinophilic Esophagitis
- Gene expression and cancer classification
- HIV Research and Treatment
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Cell Image Analysis Techniques
- Galectins and Cancer Biology
- Cancer Immunotherapy and Biomarkers
- Gene Regulatory Network Analysis
- vaccines and immunoinformatics approaches
- Cancer Research and Treatments
- Mycobacterium research and diagnosis
- Biosimilars and Bioanalytical Methods
- Bayesian Methods and Mixture Models
- Gastric Cancer Management and Outcomes
- Immune cells in cancer
- Advanced Biosensing Techniques and Applications
- Statistical Methods and Inference
- Genomics and Chromatin Dynamics
- Bioinformatics and Genomic Networks
University of Lausanne
2021-2025
SIB Swiss Institute of Bioinformatics
2022-2025
Ludwig Cancer Research
2022-2024
Fred Hutch Cancer Center
2015-2024
University of Washington
2014-2024
University Hospital of Lausanne
2021-2024
Idiap Research Institute
2024
Cancer Research Center
2014-2023
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2012-2023
Harvard University
2021-2022
The simultaneous measurement of multiple modalities represents an exciting frontier for single-cell genomics and necessitates computational methods that can define cellular states based on multimodal data. Here, we introduce "weighted-nearest neighbor" analysis, unsupervised framework to learn the relative utility each data type in cell, enabling integrative analysis modalities. We apply our procedure a CITE-seq dataset 211,000 human peripheral blood mononuclear cells (PBMCs) with panels...
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...
Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation 309 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data patient-reported symptoms. resolved four PASC-anticipating at the time diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, specific...
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...
We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics 139 COVID-19 patients representing all levels disease severity, from serial blood draws collected during first week infection following diagnosis. identify a major shift between mild moderate disease, at which point elevated inflammatory signaling is accompanied by loss specific classes metabolites metabolic processes. Within this stressed environment multiple unusual cell phenotypes emerge...
Semen contains relatively ill-defined regulatory components that likely aid fertilization, but which could also interfere with defense against infection. Each ejaculate trillions of exosomes, membrane-enclosed subcellular microvesicles, have immunosuppressive effects on cells important in the genital mucosa. Exosomes general are believed to mediate inter-cellular communication, possibly by transferring small RNA molecules. We found seminal exosome (SE) preparations contain a substantial...
We propose a fast and powerful analysis algorithm, titled Model-based Analysis of Tiling-arrays (MAT), to reliably detect regions enriched by transcription factor chromatin immunoprecipitation (ChIP) on Affymetrix tiling arrays (ChIP-chip). MAT models the baseline probe behavior considering sequence copy number each array. It standardizes value through model, eliminating need for sample normalization. uses an innovative function score ChIP enrichment, which allows robust P false discovery...
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...
How potently CAR T cells with CD28 or 4-1BB costimulatory domains stimulate intracellular signaling correlates treatment efficacy.
Abstract The simultaneous measurement of multiple modalities, known as multimodal analysis, represents an exciting frontier for single-cell genomics and necessitates new computational methods that can define cellular states based on data types. Here, we introduce ‘weighted-nearest neighbor’ unsupervised framework to learn the relative utility each type in cell, enabling integrative analysis modalities. We apply our procedure a CITE-seq dataset hundreds thousands human white blood cells...
Model-based clustering consists of fitting a mixture model to data and identifying each cluster with one its components. Multivariate normal distributions are typically used. The number clusters is usually determined from the data, often using BIC. In practice, however, individual can be poorly fitted by Gaussian distributions, in that case model-based tends represent non-Gaussian two or more distributions. If components interpreted as clusters, this lead overestimation clusters. This...
Standardized assessments of HIV-1 vaccine-elicited neutralizing antibody responses are complicated by the genetic and antigenic variability viral envelope glycoproteins (Envs). To address these issues, suitable reference strains needed that representative global epidemic. Several panels have been recommended previously, but no clear answers available on how many which best suited for this purpose. We used a statistical model selection method to identify panel Env clones from among 219...
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...
Understanding mechanisms of late/acquired cancer immunotherapy resistance is critical to improve outcomes; cellular trials offer a means probe complex tumor-immune interfaces through defined T cell/antigen interactions. We treated two patients with metastatic Merkel cell carcinoma autologous polyomavirus specific CD8+ cells and immune-checkpoint inhibitors. In both cases, dramatic remissions were associated dense infiltration activated CD8+s into the regressing tumors. However, late relapses...
Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope glycoproteins have potential mediate antiviral effector functions that could be beneficial vaccine-induced protection. Here, plasma IgG responses were assessed in three gp120 vaccine efficacy trials (RV144, Vax003, Vax004) HIV-1-infected individuals by using arrays of overlapping peptides spanning the entire consensus gp160 all major genetic subtypes circulating recombinant forms (CRFs) virus. In RV144, where...
Abstract Chimeric antigen receptor (CAR) T-cell therapy has produced remarkable anti-tumor responses in patients with B-cell malignancies. However, clonal kinetics and transcriptional programs that regulate the fate of CAR-T cells after infusion remain poorly understood. Here we perform TCRB sequencing, integration site analysis, single-cell RNA sequencing (scRNA-seq) to profile CD8 + from products (IPs) blood undergoing CD19 immunotherapy. shows diversity is highest IPs declines following...
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...