- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Identification and Quantification in Food
- Bioinformatics and Genomic Networks
- Machine Learning in Bioinformatics
- vaccines and immunoinformatics approaches
- Biomedical Text Mining and Ontologies
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Prostate Cancer Treatment and Research
- Metabolomics and Mass Spectrometry Studies
- Metabolism and Genetic Disorders
- Ubiquitin and proteasome pathways
- Gene expression and cancer classification
- Prostate Cancer Diagnosis and Treatment
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Genomics and Rare Diseases
- Genomics and Phylogenetic Studies
- Immunotherapy and Immune Responses
- Bacterial Identification and Susceptibility Testing
- Vector-borne infectious diseases
- Single-cell and spatial transcriptomics
- Mosquito-borne diseases and control
- RNA and protein synthesis mechanisms
ETH Zurich
2016-2024
Shanghai Jiao Tong University
2022-2024
Hong Kong University of Science and Technology
2011-2016
University of Hong Kong
2011-2016
United States Department of Energy
1990
Ames National Laboratory
1990
Iowa State University
1989-1990
Mass spectrometry (MS)-based immunopeptidomics investigates the repertoire of peptides presented at cell surface by major histocompatibility complex (MHC) molecules. The broad clinical relevance MHC-associated peptides, e.g. in precision medicine, provides a strong rationale for large-scale generation immunopeptidomic datasets and recent developments MS-based peptide analysis technologies now support required data. Importantly, availability diverse has resulted an increasing need to...
Down syndrome (DS) is mostly caused by a trisomy of the entire Chromosome 21 (Trisomy 21, T21). Here, we use SWATH mass spectrometry to quantify protein abundance and turnover in fibroblasts from monozygotic twin pair discordant for T21, profile expression 11 unrelated DS individuals matched controls. The integration steady-state proteomic data indicates that protein-specific degradation members stoichiometric complexes major determinant T21 gene dosage outcome, both within between...
Abstract Methylmalonic aciduria (MMA) is an inborn error of metabolism with multiple monogenic causes and a poorly understood pathogenesis, leading to the absence effective causal treatments. Here we employ multi-layered omics profiling combined biochemical clinical features individuals MMA reveal molecular diagnosis for 177 out 210 (84%) cases, majority (148) whom display pathogenic variants in methylmalonyl-CoA mutase ( MMUT ). Stratification these data layers by disease severity shows...
To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including selected reaction monitoring (SRM), parallel (PRM), massively data-independent acquisition (DIA), have been developed. For optimal performance, they require fragment ion spectra of peptides as prior knowledge. In this report, we describe a MS pipeline spectral resource to support proteomics studies human tissue samples....
Understanding the complex background of cancer requires genotype-phenotype information in single-cell resolution. Here, we perform long-read RNA sequencing (scRNA-seq) on clinical samples from three ovarian patients presenting with omental metastasis and increase PacBio depth to 12,000 reads per cell. Our approach captures 152,000 isoforms, which over 52,000 were not previously reported. Isoform-level analysis accounting for non-coding isoforms reveals 20% overestimation protein-coding gene...
Spectral library searching has been recently proposed as an alternative to sequence database for peptide identification from MS/MS. We performed a systematic comparison between spectral and using wide variety of data better demonstrate, understand, the superior sensitivity former observed in preliminary studies. By decoupling effect search space, we demonstrated that success is primarily attributable use real spectra matching, without which advantage largely disappears. further determined...
Abstract The large array of peptides presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules is referred as the MHC immunopeptidome. Although immunopeptidome ubiquitous in mammals and represents a critical component immune system, very little known, any species, about its composition across most tissues organs vivo . We applied mass spectrometry (MS) technologies draft first tissue-based atlas murine health. Peptides were extracted from 19 normal C57BL/6 mice...
Abstract Deterioration of biomolecules in clinical tissues is an inevitable pre-analytical process, which affects molecular measurements and thus potentially confounds conclusions from cohort analyses. Here, we investigate the degradation mRNA protein 68 pairs adjacent prostate tissue samples using RNA-Seq SWATH mass spectrometry, respectively. To objectively quantify extent degradation, develop a numerical score, Proteome Integrity Number (PIN), that faithfully measures degree degradation....
Human cancer cell lines are widely used in pharmacological and systems biological studies. The rapid documentation of the steady-state gene expression landscape cells a particular experiment may help to improve reproducibility scientific research. Here we applied data-independent acquisition mass spectrometry (DIA-MS) method, coupled with peptide spectral-library-free data analysis workflow, measure both proteome phosphoproteome melanoma line panel different metastatic properties. For each...
Valienamine is a valuable building block for active pharmaceuticals and agrochemicals because of its aminocyclitol structure glucosidase inhibitory activity. Straightforward amino chiral center construction on valienone using sugar aminotransferase (SAT) to produce valienamine achieved strict stereo-specificity; however, low transamination activity owing an unfavorable binding conformation the non-natural substrate in oversized substrate-binding pocket currently limits SAT-based production....
Abstract The SysteMHC Atlas v1.0 was the first public repository dedicated to mass spectrometry-based immunopeptidomics. Here we introduce a newly released version of v2.0 (https://systemhc.sjtu.edu.cn), comprehensive collection 7190 MS files from 303 allotypes. We extended and optimized computational pipeline that allows identification MHC-bound peptides carrying on unexpected post-translational modifications (PTMs), thereby resulting in 471K modified identified over 60 distinct PTM types....
The magic-angle spinning $^{29}\mathrm{Si}$ NMR of annealed rf-sputter-deposited amorphous silicon was measured as a function annealing temperature up to crystallization. peak width is observed narrow significantly with little change in position. A comparison Raman-scattering and neutron-diffraction results indicates that the distribution chemical shifts modified by variations electronic density states bond-angle distribution.
Abstract Protein complexes are responsible for the enactment of most cellular functions. For protein complex to form and function, its subunits often need be present at defined quantitative ratios. Typically, global changes in composition assessed with experimental approaches that tend time consuming. Here, we have developed a computational algorithm detection altered based on systematic assessment subunit ratios from proteomic measurements. We applied it measurements breast cancer cell...
Gleason grading is an important prognostic indicator for prostate adenocarcinoma and crucial patient treatment decisions. However, intermediate-risk patients diagnosed in the grade group (GG) 2 GG3 can harbour either aggressive or non-aggressive disease, resulting under- overtreatment of a significant number patients. Here, we performed proteomic, differential expression, machine learning, survival analyses 1,348 matched tumour benign sample runs from 278 Three proteins (F5, TMEM126B, EARS2)...
Spectral library searching is a maturing approach for peptide identification from MS/MS, offering an alternative to traditional sequence database searching. relies on direct spectrum-to-spectrum matching between the query data and spectral library, which affords better discrimination of true false matches, leading improved sensitivity. However, due inherent diversity peak location intensity profiles real spectra, resulting similarity score distributions often take unpredictable shapes. This...
Preeclampsia (PE) is a severe pregnancy complication, which may be considered as systemic response in the second half of to physiological failures first trimester, and can lead very serious consequences for health mother fetus. Since PE often associated with proteinuria, urine proteomic assays represent powerful tool timely diagnostics appropriate management. High resolution mass spectrometry was applied peptidome analysis 127 samples pregnant women various hypertensive complications:...
Abstract Shotgun proteomics is an emerging tool for bacterial identification and differentiation. However, the of mass spectra peptides to genome-derived peptide sequences remains a key issue that limits use shotgun bacteria with genome available. In this proof-of-concept study, we report novel fingerprinting method enjoys resolving power accuracy spectrometry without burden (i.e. sequence-independent). This uses similarity-clustering algorithm search are derived from same merge them into...
With the rapid accumulation of data from shotgun proteomics experiments, it has become feasible to build comprehensive and high-quality spectral libraries tandem mass spectra peptides. A library condenses experimental into a retrievable format can be used aid peptide identification by searching. key step in building is spectrum denoising, which best accomplished merging multiple replicates same ion consensus spectrum. However, this approach cannot applied "singleton spectra," for only one...
Abstract Multi-layered omics approaches can help define relationships between genetic factors, biochemical processes and phenotypes thus extending research of inherited diseases beyond identifying their monogenic cause 1 . We implemented a multi-layered approach for the metabolic disorder methylmalonic aciduria (MMA). performed whole genome sequencing, transcriptomic mass spectrometry-based proteotyping from matched primary fibroblast samples 230 individuals (210 affected, 20 controls)...
ABSTRACT To answer the increasing need for detecting and validating protein biomarkers in clinical specimens, proteomic techniques are required that support fast, reproducible quantitative analysis of large sample cohorts. Targeted mass spectrometry techniques, specifically SRM, PRM massively parallel SWATH/DIA technique have emerged as a powerful method biomarker research. For optimal performance, they require prior knowledge about fragment ion spectra targeted peptides. In this report, we...