A5008709977- Monoclonal and Polyclonal Antibodies Research
- Influenza Virus Research Studies
- T-cell and B-cell Immunology
- Protein purification and stability
- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- HIV Research and Treatment
- Evolution and Genetic Dynamics
- Viral Infections and Outbreaks Research
- vaccines and immunoinformatics approaches
- Viral Infections and Vectors
- Hepatitis B Virus Studies
- Multiple Sclerosis Research Studies
- Advanced Proteomics Techniques and Applications
- Plant Virus Research Studies
- Extracellular vesicles in disease
- Tryptophan and brain disorders
- T-cell and Retrovirus Studies
- Genomics and Rare Diseases
- Polyomavirus and related diseases
- Chronic Lymphocytic Leukemia Research
- Peripheral Neuropathies and Disorders
University of California, San Francisco
2013-2023
Institute of Biomedical Science
2023
McGill University
2023
University of California System
2016
Abstract Profiling immunoglobulin (Ig) receptor repertoires with specialized assays can be cost-ineffective and time-consuming. Here we report ImReP, a computational method for rapid accurate profiling of the Ig repertoire, including complementary-determining region 3 (CDR3), using regular RNA sequencing data such as those from 8,555 samples across 53 tissues types 544 individuals in Genotype-Tissue Expression (GTEx v6) project. Using ImReP GTEx v6 data, generate collection 3.6 million...
High intracellular pH in cancer cells enables the oncogenic effects of Arg-to-His mutations proteins.
High-throughput RNA-sequencing (RNA-seq) technologies provide an unprecedented opportunity to explore the individual transcriptome. Unmapped reads are a large and often overlooked output of standard RNA-seq analyses. Here, we present Read Origin Protocol (ROP), tool for discovering source all originating from complex RNA molecules. We apply ROP samples across 2630 individuals 54 diverse human tissues. Our approach can account 99.9% 1 trillion various read length. Additionally, use...
Multiple sclerosis (MS) is a complex genetically mediated autoimmune disease of the central nervous system where anti-CD20-mediated B cell depletion remarkably effective in treatment early disease. While previous studies investigated effect on select immune subsets using flow cytometry-based methods, therapeutic impact patient landscape unknown. In this study, we explored how depleting therapies modulate single-cell RNA sequencing (scRNAseq). We demonstrate that leads to type-specific...
Vaccines dramatically affect an individual's adaptive immune system and thus provide excellent means to study human immunity. Upon vaccination, the B cells that express antibodies (Abs) happen bind vaccine are stimulated proliferate undergo mutagenesis at their Ab locus. This process may alter composition of cell lineages within individual, which known collectively as antibody repertoire (AbR). Antibodies also highly expressed in whole blood, potentially enabling RNA sequencing (RNA-seq)...
Cancer can be viewed as a set of different diseases with distinctions based on tissue origin, driver mutations, and genetic signatures. Accordingly, each these have been used to classify cancer subtypes reveal common features. Here, we present analysis amino acid mutation Non-negative Matrix Factorization principal component 29 cancers revealed six signatures, including four signatures that were dominated by either arginine histidine (Arg>His) or glutamate lysine (Glu>Lys) mutations....
The B cell-depleting anti-CD20 antibody ocrelizumab (OCR) effectively reduces MS disease activity and slows disability progression. Given the role of cells as antigen-presenting cells, primary goal this study was to evaluate effect OCR on T-cell receptor repertoire diversity.
Targeted B-cell depletion is a useful therapy for many diseases, including autoimmune disorders and certain cancers. We developed sensitive blood assay, MRB 1.1, compared its performance with the T-cell/B-cell/NK-cell (TBNK) assessed different therapies. The empirically defined lower limit of quantification (LLOQ) CD19+ cells in TBNK assay was 10 cells/μL, 0.441 cells/μL 1.1 assay. LLOQ used to compare differences between similar lupus nephritis patient populations who received rituximab...
Abstract Assay-based approaches provide a detailed view of the adaptive immune system by profiling immunoglobulin (Ig) receptor repertoires. However, these methods carry high cost and lack scale standard RNA sequencing (RNA-Seq). Here we report development ImReP, novel computational method for rapid accurate repertoire from regular RNA-Seq data. ImReP can also accurately assemble complementary determining regions 3 (CDR3s), most variable Ig receptors. We applied our to 8,555 samples across...
Abstract The interaction between human immunodeficiency virus (HIV) and the antibody repertoire (AbR) during chronic infection can provide important information for HIV vaccine research, yet has not been well-characterized on a systems level. We deeply sequenced population AbR of ten HIV-infected, antiretroviral (ART)-naïve individuals, each with 10-20 longitudinal samples spanning 4-14 years. Our unbiased sequencing approach identified partitions AbRs showing evidence autologous...
ABSTRACT Cancer can be viewed as a set of different diseases with distinctions based on tissue origin, driver mutations, and genetic signatures. Accordingly, each these have been used to classify cancer subtypes reveal common features. Here, we present analysis amino acid mutation Non-negative Matrix Factorization principal component 29 cancers revealed six signatures, including four signatures that were dominated by either arginine histidine (Arg>His) or glutamate lysine (Glu>Lys)...
Abstract Background Vaccines dramatically affect an individual’s adaptive immune system, and thus provide excellent means to study human immunity. Upon vaccination, the B cells that express antibodies (Abs) happen bind vaccine are stimulated proliferate undergo mutagenesis at their Ab locus. This process may alter composition of cell lineages within individual, which known collectively as antibody repertoire (AbR). Antibodies also highly expressed in whole blood, potentially enabling...
Multiple sclerosis (MS) is a heterogeneous immune-mediated disorder of the central nervous system, and primary progressive MS (PPMS) characterized by insidious injury independent clinical relapses from disease onset. Predicting progression remains an unmet need across spectrum. We evaluated statistical machine learning (ML) models for predicting in 596 patients with PPMS ORATORIO, randomized, placebo (PBO)-controlled, phase 3 study ocrelizumab (OCR). Using baseline clinical, magnetic...
Ebola virus (EBOV) disease is a viral hemorrhagic fever with high case-fatality rate in humans. This caused by four members of the filoviral genus Ebolavirus, including EBOV. The natural hosts reservoirs ebolaviruses remain to be identified. Glycoprotein 2 reptarenaviruses, known infect only boa constrictors and pythons, similar sequence structure ebolaviral glycoprotein 2, suggesting that EBOV may able reptilian cells. Therefore, we serially passaged distantly related filovirus, Marburg...
To assess the impact of ocrelizumab (OCR) treatment on blood B cells and B-cell subsets in patients with relapsing multiple sclerosis (RMS) from OPERA I (NCT01247324) II (NCT01412333) trials.
ABSTRACT Ebola virus disease (EVD) is a viral hemorrhagic fever with high case-fatality rate in humans. EVD caused by four members of the filoviral genus Ebolavirus , (EBOV) being most notorious one. Although bats are discussed as potential ebolavirus reservoirs, limited data actually support this hypothesis. Glycoprotein 2 (GP2) reptarenaviruses, known to infect only boa constrictors and pythons, similar sequence structure ebolaviral glycoprotein (GP2), suggesting that EBOV may be able...
Abstract High throughput RNA sequencing technologies have provided invaluable research opportunities across distinct scientific domains by producing quantitative readouts of the transcriptional activity both entire cellular populations and single cells. The majority RNA-Seq analyses begin mapping each experimentally produced sequence (i.e., read) to a set annotated reference sequences for organism interest. For biological technical reasons, significant fraction reads remains unmapped. In...