- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Advanced Proteomics Techniques and Applications
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Mass Spectrometry Techniques and Applications
- Multiple Myeloma Research and Treatments
- Scientific Computing and Data Management
- Blood groups and transfusion
- Metabolomics and Mass Spectrometry Studies
- Respiratory viral infections research
- Enzyme Structure and Function
- Research Data Management Practices
- Parvovirus B19 Infection Studies
- scientometrics and bibliometrics research
- Machine Learning in Bioinformatics
- T-cell and B-cell Immunology
- Platelet Disorders and Treatments
- SARS-CoV-2 and COVID-19 Research
- Virology and Viral Diseases
- Cancer Genomics and Diagnostics
Utrecht University
2020-2025
Netherlands Metabolomics Centre
2023
Although humans can produce billions of IgG1 variants through recombination and hypermutation, the diversity clones circulating in human blood plasma has largely eluded direct characterization. Here, we combined several mass-spectrometry-based approaches to reveal that repertoire is dominated by a limited number healthy donors septic patients. We observe each individual donor exhibits unique serological repertoire, which remains stable over time but adapt rapidly changes physiology....
Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells mucosal surfaces. MUC1 has barrier function against bacterial invasion and well known for its aberrant expression glycosylation in adenocarcinomas. The extracellular domain contains variable number tandem repeats (VNTR) 20 amino acids, which are heavily O -linked glycosylated. Monoclonal antibodies VNTR powerful research tools with applications diagnosis treatment MUC1-expressing cancers. Here, we...
Abstract The Respiratory Syncytial Virus (RSV) Fusion (F) protein is a major target of antiviral antibodies following natural infection or vaccination and responsible for mediating fusion between the viral envelope host membrane. process driven by large-scale conformational change in F, switching irreversibly from metastable prefusion state to stable postfusion conformation. Previous research has identified six distinct antigenic sites RSV-F, termed Ø, I, II, III, IV, V. Of these, only site...
Accurate and comprehensive peptide spectrum annotation is a crucial step to interpret mass spectrometry-based proteomics data. While peak assignment in fragmentation spectra central broad range of applications, current tools tend be specialized specific task. Here we present more tool, the Annotator, which unifies for bottom-up, middle-down, top-down, cross-linked, glycopeptide spectra, from all methods, including ion types: a/b/c, x/y/z, d/v/w, immonium ions. The Annotator integrates known...
Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder characterized by the presence predominant monoclonal antibody (i.e., M-protein) in serum, without clinical symptoms. Here we present case study which detect MGUS liquid-chromatography coupled with mass spectrometry (LC-MS) profiling IgG1 human serum. We detected Fab-glycosylated M-protein and determined full heavy light chain sequences bottom-up proteomics techniques using multiple proteases, further...
Antibody sequences can be determined at 99% accuracy directly from the polypeptide product by using bottom-up proteomics techniques. Sequencing peptide level is limited isobaric residues leucine and isoleucine, incomplete fragmentation spectra in which order of two or more remains ambiguous due to lacking fragment ions for intermediate positions, combinations amino acids, potentially different lengths, example, GG = N GA Q. Here, we present several updates Stitch (v1.5), performs...
Abstract Antibody sequences can be determined at 99% accuracy directly from the polypeptide product using bottom-up proteomics techniques. This circumvents need to isolate antibody-producing B-cell clone and enables reverse engineering of monoclonal antibodies lost hybridoma cell lines, as well secreted protein in bodily fluid. Sequencing peptide level is limited by common mass coincidences isobaric residues like leucine/isoleucine, but also incomplete fragmentation spectra which order two...
Serum proteomics has matured and is now able to monitor hundreds of proteins quantitatively in large cohorts patients. However, the fine characteristics some most dominant serum, immunoglobulins, are these studies often ignored, due their vast, highly personalized, diversity sequences. Here, we focus exclusively on personalized features serum proteome distinctively chose study individual samples from a low population: elderly donors infected by severe acute respiratory syndrome corona virus...
Mass spectral libraries are collections of reference spectra, usually associated with specific analytes from which the spectra were generated, that used for further downstream analysis new spectra. There many different formats encoding libraries, but none have undergone a standardization process to ensure broad applicability applications. As part Human Proteome Organization Proteomics Standards Initiative (PSI), we developed standardized format called mzSpecLib...
Antibodies are a major component of adaptive immunity against invading pathogens. Here, we explore possibilities for an analytical approach to characterize the antigen-specific antibody repertoire directly from secreted proteins in convalescent serum. This aims perform simultaneous sequencing and epitope mapping using combination single particle cryo-electron microscopy (cryoEM) bottom-up proteomics techniques based on mass spectrometry (LC-MS/MS). We evaluate performance deep-learning tool...
Antibodies are a major component of adaptive immunity against invading pathogens. Here we explore possibilities for an analytical approach to characterize the antigen-specific antibody repertoire directly from secreted proteins in convalescent serum. This aims perform simultaneous sequencing and epitope mapping using combination single particle cryo-electron microscopy (cryoEM) bottom-up proteomics techniques based on mass spectrometry (LC-MS/MS). We evaluate performance deep-learning tool...
Abstract Recently, a conceptually new mass analyzer was introduced by pairing quadrupole Orbitrap spectrometer with an asymmetric track lossless (Astral™) analyzer. This system provides >200 Hz MS/MS scanning speed, high resolving power, sensitivity, and accuracy. Due to its the instrument allows for narrow-window data-independent acquisition (nDIA) strategy, representing technical milestone in peptide-centric proteomics. However, this may also be applied other complex clinically...
Antibodies are a major component of adaptive immunity against invading pathogens. Here we explore possibilities for an analytical approach to characterize the antigen-specific antibody repertoire directly from secreted proteins in convalescent serum. This aims perform simultaneous sequencing and epitope mapping using combination single particle cryo-electron microscopy (cryoEM) bottom-up proteomics techniques based on mass spectrometry (LC-MS/MS). We evaluate performance deep-learning tool...
Antibodies are a major component of adaptive immunity against invading pathogens. Here, we explore possibilities for an analytical approach to characterize the antigen-specific antibody repertoire directly from secreted proteins in convalescent serum. This aims perform simultaneous sequencing and epitope mapping using combination single particle cryo-electron microscopy (cryoEM) bottom-up proteomics techniques based on mass spectrometry (LC-MS/MS). We evaluate performance deep-learning tool...
The ability to sequence proteins without reliance on a genomic template defines critical frontier in modern proteomics. This approach, known as de novo protein sequencing, is essential for applications such antibody microbiome proteomics, and antigen discovery, which require accurate reconstruction of peptide sequences. While trypsin remains the gold-standard protease its restricted cleavage specificity limits diversity. constraint especially problematic where functionally regions often lack...
Abstract Antibodies are a major component of adaptive immunity against invading pathogens. Here we explore possibilities for an analytical approach to characterize the antigen-specific antibody repertoire directly from secreted proteins in convalescent serum. This aims perform simultaneous sequencing and epitope mapping using combination single particle cryo-electron microscopy (cryoEM) bottom-up proteomics techniques based on mass spectrometry (LC-MS/MS). We evaluate performance...
Mass spectral libraries are collections of reference spectra, usually associated with specific analytes from which the spectra were generated, that used for further downstream analysis new spectra. There many different formats encoding libraries, but none have undergone a standardization process to ensure broad applicability applications. As part Human Proteome Organization Proteomics Standards Initiative (PSI), we developed standardized format called mzSpecLib...
Abstract Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells different mucosal surfaces including breast and intestine. In gastrointestinal tract, MUC1 has barrier function against bacterial invasion, but can also serve as an entry receptor for pathogenic Salmonella bacteria. Moreover, well known its aberrant expression glycosylation in adenocarcinomas The extracellular domain contains variable number tandem repeats (VNTR) 20 amino acids, which are...
Abstract Recently, a conceptually new mass analyzer was introduced by pairing quadrupole Orbitrap spectrometer with an asymmetric track lossless (Astral ™ ) analyzer. This system provides >200-Hz MS/MS scanning speed, high resolving power and sensitivity, low-ppm accuracy. instrument allows narrow-window data-independent (nDIA) strategy, improving sensitivity reproducibility even when using very short LC gradients. Although this represents technical milestone in peptide-centric...
As recognition of the vital importance software for contemporary research is increasing, Research Software Engineering (RSE) emerging as a discipline in its own right. We present an inventory relevant questions about RSE basis future and initiatives to advance field, highlighting selected literature initiatives. This work outcome community workshop held part 2020 International Series Online Events (SORSE) which identified prioritized key across three overlapping themes: people, policy...
The human body produces a vast variety of circulating immunoglobulins (Igs) to recognize and combat pathogens other non-self molecular components. In plasma the most abundant class Igs is immunoglobulin G subclass I (IgG1) 1. Through somatic recombination hypermutation, our bodies can theoretically produce several billions distinct IgG1 variants 2,3. available repertoire thereby far exceeds physical number memory B cells 4. theoretical possibilities are highly suggestive vastly complex...
Abstract Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder, characterized by the presence predominant monoclonal antibody ( i . e ., M-protein) in serum, without clinical symptoms. Here we present case study which detect MGUS liquid-chromatography coupled with mass spectrometry (LC-MS) profiling IgG1 human serum. We detected Fab-glycosylated M-protein and determined full heavy light chain sequences bottom-up proteomics techniques using multiple proteases,...