A5067355729- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Genomics and Phylogenetic Studies
- Genetics, Bioinformatics, and Biomedical Research
- Scientific Computing and Data Management
- Molecular Biology Techniques and Applications
- Gene expression and cancer classification
- Atmospheric chemistry and aerosols
- Biomedical Text Mining and Ontologies
- Urban Heat Island Mitigation
- Analytical Chemistry and Chromatography
- Distributed and Parallel Computing Systems
- Building Energy and Comfort Optimization
- Receptor Mechanisms and Signaling
- Amino Acid Enzymes and Metabolism
- Bioinformatics and Genomic Networks
- Glycosylation and Glycoproteins Research
- Machine Learning in Bioinformatics
- Atmospheric and Environmental Gas Dynamics
- SARS-CoV-2 detection and testing
- Alzheimer's disease research and treatments
- Biosensors and Analytical Detection
- Nicotinic Acetylcholine Receptors Study
- Congenital Anomalies and Fetal Surgery
Children's Hospital Research Institute of Manitoba
2023-2025
University of Manitoba
2023-2025
Northwestern University
2014-2023
Air Canada
2017
Université Laval
2015-2016
Indiana University Bloomington
2012-2015
Washington University in St. Louis
2008-2014
University of Wisconsin–Madison
2011-2013
Great Lakes Bioenergy Research Center
2011-2013
National Cancer Institute
2008
Many top-down proteomics experiments focus on identifying and localizing PTMs other potential sources of “mass shift” a known protein sequence. A simple application to match ion masses facilitate the iterative hypothesis testing PTM presence location would assist with data analysis in these experiments. ProSight Lite is free software tool for matching single candidate sequence against set mass spectrometric observations. Fixed or variable modifications, including both select number...
Human biology is tightly linked to proteins, yet most measurements do not precisely determine alternatively spliced sequences or posttranslational modifications. Here, we present the primary structures of ~30,000 unique proteoforms, nearly 10 times more than in previous studies, expressed from 1690 human genes across 21 cell types and plasma blood bone marrow. The results, compiled Blood Proteoform Atlas (BPA), indicate that proteoforms better describe protein-level are specific indicators...
ProSight PTM 2.0 (http://prosightptm2.scs.uiuc.edu) is the next generation of web-based system for identification and characterization proteins using top down tandem mass spectrometry. It introduces an entirely new data-driven interface, integrated Sequence Gazer protein characterization, support fixed modifications, terminal modifications improved multiple precursor ions (multiplexing). Furthermore, it supports data import export local analysis collaboration.
ProSight PTM (https://prosightptm.scs.uiuc.edu/) is a web application for identification and characterization of proteins using mass spectra data from 'top-down' fragmentation intact protein ions (i.e. without any tryptic digestion). has many tools graphical features to facilitate analysis single proteins, in mixtures fragmented parallel. Sequence databases across the phylogenetic tree are supported, with new database strategy 'shotgun annotation' used assist wild-type proteins. During...
Quantitative proteomics has focused heavily on correlating protein abundances, ratios, and dynamics by developing methods that are expression-centric (e.g. isotope coded affinity tag, isobaric tag for relative absolute quantification, etc.). These effectively detect changes in abundance but fail to provide a comprehensive perspective of the diversity proteins such as histones, which regulated post-translational modifications. Here, we report characterization modified forms HeLa cell histone...
Amyloid-beta (Aβ) plays a key role in the pathogenesis of Alzheimer's disease (AD), but little is known about proteoforms present AD brain. We used high-resolution mass spectrometry to analyze intact Aβ from soluble aggregates and insoluble material brains six cases with severe dementia pathologically confirmed AD. The are especially relevant because they believed be most toxic form Aβ. found diversity peptides, 26 unique including various N- C-terminal truncations. truncations comprised 73%...
With the prospect of resolving whole protein molecules into their myriad proteoforms on a proteomic scale, question quantitative analysis in discovery mode comes to fore. Here, we demonstrate robust pipeline for identification and stringent scoring abundance changes forms <30 kDa complex system. The input is ∼100–400 μg total each biological replicate, outputs are graphical displays depicting statistical confidence metrics proteoform (i.e., volcano plot representations technical variation)....
Pilot Project #1--the identification and characterization of human histone H4 proteoforms by top-down MS--is the first project launched Consortium for Top-Down Proteomics (CTDP) to refine validate MS. Within initial results from seven participating laboratories, all reported probability-based (UniProt accession P62805) with expectation values ranging 10(-13) 10(-105). Regarding characterization, a total 74 were reported, 21 done so unambiguously; one new PTM, K79ac, was identified....
Mutations of the
Successful high-throughput characterization of intact proteins from complex biological samples by mass spectrometry requires instrumentation capable high resolving power, accuracy, sensitivity, and spectral acquisition rate. These limitations often necessitate the performance hundreds LC-MS/MS experiments to obtain reasonable coverage targeted proteome, which is still typically limited molecular weights below 30 kDa. The National High Magnetic Field Laboratory (NHMFL) recently installed a 21...
The automated processing of data generated by top down proteomics would benefit from improved scoring for protein identification and characterization highly related forms (proteoforms). Here we propose the "C-score" (short Characterization Score), a Bayesian approach to proteoform problem, implemented within framework allow infusion expert knowledge into generative models that take advantage known properties proteins analytical systems (e.g., fragmentation propensities, "off-by-1 Da"...
The analysis of intact proteins (top-down strategy) by mass spectrometry has great potential to elucidate proteoform variation, including patterns post-translational modifications (PTMs), which may not be discernible peptides alone (bottom-up approach). To maximize sequence coverage and localization PTMs, various fragmentation modes have been developed produce fragment ions from deep within proteins. Ultraviolet photodissociation (UVPD) recently shown high PTM retention on a variety...
Over the past decade, developments in high resolution mass spectrometry have enabled throughput analysis of intact proteins from complex proteomes, leading to identification thousands proteoforms. Several previous reports on top-down proteomics (TDP) relied hybrid ion trap–Fourier transform spectrometers combined with data-dependent acquisition strategies. To further reduce TDP practice, we use a quadrupole-Orbitrap instrument coupled software for proteoform-dependent data identify and...
Bottom-up proteomics relies on the use of proteases and is method choice for identifying thousands protein groups in complex samples. Top-down has been shown to be robust direct analysis small proteins offers a solution "peptide-to-protein" inference problem inherent with bottom-up approaches. Here, we describe first large-scale integration genomic, top-down proteomic data comparative patient-derived mouse xenograft models basal luminal B human breast cancer, WHIM2 WHIM16, respectively....
RNA-sequencing is a technique to study RNA expression in biological material. It quickly gaining popularity the field of transcriptomics. Trinity software tool that was developed for efficient de novo reconstruction transcriptomes from RNA-Seq data. In this paper we first conduct performance and compare it previously published data 2011. The version 2011 much slower than many other assemblers biologists have thus been forced choose between quality speed. We examine runtime behavior as whole...
Fragmentation of intact proteins in the gas phase is influenced by amino acid composition, mass and charge precursor ions, higher order structure, dissociation technique used. The likelihood fragmentation occurring between a pair residues referred to as propensity calculated dividing total number assigned events possible for each residue pair. Here, we describe general propensities when performing top-down spectrometry (TDMS) using denaturing or native electrospray ionization. A 5311 matched...