A5076759120- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- Advanced Proteomics Techniques and Applications
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Evolutionary Algorithms and Applications
- Viral Infections and Outbreaks Research
- Metaheuristic Optimization Algorithms Research
- Advanced Multi-Objective Optimization Algorithms
- Peptidase Inhibition and Analysis
- Machine Learning in Bioinformatics
- Ubiquitin and proteasome pathways
- Genomics and Phylogenetic Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Viral gastroenteritis research and epidemiology
- Hepatitis B Virus Studies
- Bacterial Genetics and Biotechnology
- SARS-CoV-2 detection and testing
- Viral Infections and Vectors
- Microbial Community Ecology and Physiology
- Single-cell and spatial transcriptomics
- Immunotherapy and Immune Responses
- Anomaly Detection Techniques and Applications
- Time Series Analysis and Forecasting
Digital Proteomics (United States)
2017-2021
University of California, San Diego
2012-2016
St Petersburg University
2015
GE Global Research (United States)
2001-2007
General Electric (United States)
2007
N-terminal methionine excision (NME) and acetylation (NTA) are two of the most common protein post-translational modifications. NME is a universally conserved activity highly specific mechanism across all life forms. NTA very in eukaryotes but occurs rarely prokaryotes. By analyzing data sets from yeast, mammals bacteria (including 112 million spectra 57 bacterial species), largest comparative proteogenomics study to date, it shown that previous assumptions/perceptions about specificity...
Nanobodies, a subclass of antibodies found in camelids, are versatile molecular binding scaffolds composed single polypeptide chain. The small size nanobodies bestows multiple therapeutic advantages (stability, tumor penetration) with the first approval 2018 cementing clinical viability this format. Structured data and sequence information will enable accelerated development nanobody-based therapeutics. Though nanobody structure deposited public domain at an accelerating pace, heterogeneity...
Abstract The analysis of concentrations circulating antibodies in serum (antibody repertoire) is a fundamental, yet poorly studied, problem immunoinformatics. two current approaches to the antibody repertoires [next generation sequencing (NGS) and mass spectrometry (MS)] present difficult computational challenges since are not directly encoded germline but extensively diversified by somatic recombination hypermutations. Therefore, protein database required for interpretation spectra from...
Aiming toward an improved understanding of the regulation proteins in cancer, recent studies from Clinical Proteomic Tumor Analysis Consortium (CPTAC) have focused on analyzing cancer tissue using proteomic technologies and workflows. Although many proteogenomics approaches for study samples been proposed, serious methodological challenges remain, especially identification multiple mutational variants or structural variations such as fusion gene events. In addition, although immune system...
Understanding the human antibody response to emerging viral pathogens is key epidemic preparedness. As size of B cell a pathogenic-virus-protective antigen poorly defined, we perform deep paired heavy- and light-chain sequencing in Ebola virus glycoprotein (EBOV-GP)-specific memory cells, allowing analysis ebolavirus-specific repertoire both genetically functionally. This approach facilitates investigation molecular genetic basis for evolution cross-reactive antibodies by elucidating...
The rapid spread of SARS-CoV-2 and its continuing impact on human health has prompted the need for effective development monoclonal antibody therapeutics. In this study, we investigate polyclonal antibodies in serum B cells from whole blood three donors with immunity to find high-affinity anti-SARS-CoV-2 escape variants. Serum IgG were selected by their affinity receptor-binding domain (RBD) non-RBD sites spike protein Omicron subvariant B.1.1.529 each donor. Antibodies analyzed bottom-up...
ABSTRACT Signal peptides are a cornerstone mechanism for cellular protein localization, yet until now experimental determination of signal has come from only narrow taxonomic sampling. As result, the dominant view is that Sec-cleaved in prokaryotes defined by canonical AxA motif. Although other residues permitted motif, alanine far most common. Here we broadly examine proteomics data to reveal peptide sequences 32 bacterial and archaeal organisms nine phyla demonstrate this preference not...
Summary Over the last 5 years proteogenomics (using mass spectroscopy to identify proteins predicted from genomic sequences) has emerged as a promising approach high‐throughput identification of protein N ‐termini, which remains problem in genome annotation. Comparison experimentally determined ‐termini with those by sequence analysis tools allows signal peptides and therefore conclusions on cytoplasmic or extracytoplasmic (periplasmic extracellular) localization respective proteins. We...
Immunotherapy is becoming increasingly important in the fight against cancers, using and manipulating body's immune response to treat tumors. Understanding repertoire-the collection of immunological proteins-of treated untreated cells possible at genomic, but technically difficult protein level. Standard databases do not include highly divergent sequences somatic rearranged immunoglobulin genes, may lead miss identifications a mass spectrometry search. We introduce novel proteogenomic...
A bstract Rabbits are a model for immunology studies, and monoclonal antibodies developed from rabbits have been sought after to empower immunoassays in variety of applications. High-throughput characterization circulating serum response specific antigens is highly impactful both humoral studies antibody development. combination high throughput sequencing transcripts B cells proteomic analysis antibodies, an approach referred as immunoproteogenomics, applied profile the immune β...
The somatic recombination of V, D, and J gene segments in B-cells introduces a great deal diversity, divergence from reference segments. Many recent studies antibodies focus on the population antibody transcripts that show which have been favored for particular antigen, repertoire. To properly describe repertoire, each must be labeled by its constituting segment, task made difficult hypermutation events. While previous approaches to repertoire analysis were based sequential alignments, we...
Three clinically relevant ebolaviruses - Ebola (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) viruses, are responsible for severe disease occasional deadly outbreaks in Africa. The largest virus (EVD) epidemic to date 2013-2016 West Africa highlighted the urgent need countermeasures, leading development FDA approval of vaccine rVSV-ZEBOV (Ervebo®) 2020 two monoclonal antibody (mAb)-based therapeutics (Inmazeb® [atoltivimab, maftivimab, odesivimab-ebgn] Ebanga® (ansuvimab-zykl) 2020. humoral...
The majority of research in evolvable hardware is focused on evolving logic for deployment reconfigurable hardware. There are far fewer reports concerned with the implementation evolutionary algorithms (EAs) focus our directed toward using as a means to speed up search, and particular multiobjective optimization (EMO). Evolutionary utilizes an search find solutions difficult problems. We present EMO algorithm hardware, discuss how it may be utilized practical situations
In multi-objective optimization (MOO) problems we need to optimize many possibly conflicting objectives. For instance, in manufacturing planning might want minimize the cost and production time while maximizing product's quality. We propose use of evolutionary algorithms (EAs) solve these problems. Solutions are represented as individuals a population assigned scores according fitness function that determines their relative Strong solutions selected for reproduction, pass genetic material...
Diagnostics and prognostics is particularly challenging in systems with a restricted suite of sensors; e.g., aircraft engines where harsh operating conditions, weight considerations, regulatory concerns limit the number sensors. In this paper, we investigate anomaly detection techniques subject to these constraints. Specifically, use as input only controller-generated, log-data for system. While such not designed carry predictive information related system health, show that it possible...
Abstract Nanobodies, a subclass of antibodies found in camelids, are versatile molecular binding scaffold composed single polypeptide chain. The small size nanobodies bestows multiple therapeutic advantages (stability, tumor penetration) with the first approval 2018 cementing clinical viability this format. Structured data and sequence information will enable accelerated development nanobody-based therapeutics. Though nanobody structure deposited public domain at an accelerating pace,...
SUMMARY Understanding the human antibody response to emerging viral pathogens is key epidemic preparedness. As size of B cell a pathogenic virus protective antigen undefined, we performed deep paired heavy and light chain sequencing in EBOV-GP specific memory cells, allowing analysis ebolavirus-specific repertoire both genetically functionally. This approach facilitated investigation molecular genetic basis for evolution cross-reactive antibodies by elucidating germline-encoded properties...
The rapid spread of SARS-CoV2 and continuing impact on human health has prompted the need for effective development monoclonal antibody therapeutics. In this study, we interrogate polyclonal antibodies in serum B cells from whole blood three donors with immunity to find high-affinity anti-SARS-CoV2 escape variants. Serum IgG were selected by affinity receptor-binding domain (RBD) non-RBD sites spike protein Omicron subvariant B.1.1.529 each donor. Antibodies analyzed bottom-up mass...
Abstract The circulating antibody repertoire is crucial for immune protection, holding significant immunological and biotechnological value. While bottom-up mass spectrometry (MS) the most widely used proteomics technique profiling sequence diversity of antibodies (Ab-seq), it has not been thoroughly benchmarked. We quantified replicability robustness Ab-seq using six monoclonal with known protein sequences in 70 different combinations concentration oligoclonality, both without polyclonal...
There are many approaches to solving multi-objective optimization problems using evolutionary algorithms. We need select methods for representing and aggregating preferences, as well choosing strategies searching in multi-dimensional objective spaces. First we suggest the use of linguistic variables represent preferences fuzzy rule systems implement tradeoff aggregations. After a review alternatives EA optimizations, explore multi-sexual genetic algorithms (MSGA). In MSGA, modify certain...
Immunotherapy is becoming increasingly important in the fight against cancers, utilizing and manipulating body's immune response to treat tumors. Understanding repertoire - collection of immunological proteins treated untreated cells possible at genomic, but technically difficult protein level. Standard databases do not include highly divergent sequences somatic rearranged immunoglobulin genes, may lead missed identifications a mass spectrometry search. We introduce novel proteogenomic...
ABSTRACT Immunoglobulins are highly diverse, diverging from their originating germline genes driven primarily by somatic recombination and hypermutation. However, gene conversion is a strong driver of immunoglobulin diversity in some species, including rabbits chickens. It considerably harder to detect sequence analysis than point mutations, currently no dedicated tools exist for identifying these events. We present GECCO , the first identification tool immunoglobulins based on modified,...