A5060210855- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Advanced Chemical Physics Studies
- Spectroscopy and Quantum Chemical Studies
- Muscle metabolism and nutrition
- Mitochondrial Function and Pathology
- Gene expression and cancer classification
- Endoplasmic Reticulum Stress and Disease
- Machine Learning in Bioinformatics
- Photochemistry and Electron Transfer Studies
- Analytical Chemistry and Chromatography
- Liver Disease Diagnosis and Treatment
- Cancer Cells and Metastasis
- Hippo pathway signaling and YAP/TAZ
- Bioinformatics and Genomic Networks
- Synthesis and Properties of Aromatic Compounds
- Connexins and lens biology
- Enzyme Structure and Function
- Advanced Glycation End Products research
- Microbial Metabolic Engineering and Bioproduction
- Alzheimer's disease research and treatments
- Adipose Tissue and Metabolism
- Genomics and Phylogenetic Studies
- Advanced Biosensing Techniques and Applications
The University of Texas Medical Branch at Galveston
2015-2024
John Sealy Hospital
2016
Galveston College
2016
Laboratoire de Biochimie
2014
Institute of Cytochemistry and Molecular Pharmacology
2012
Center for Molecular Medicine and Immunology
2012
University of Wisconsin–Madison
2009
Thermo Fisher Scientific (United States)
2006-2007
Scripps Research Institute
2002-2005
University of California, Los Angeles
2002
Proteomic analysis of complex protein mixtures using proteolytic digestion and liquid chromatography in combination with tandem mass spectrometry is a standard approach biological studies. Data-dependent acquisition used to automatically acquire spectra peptides eluting into the spectrometer. In more complicated mixtures, for example, whole cell lysates, data-dependent incompletely samples among peptide ions present rather than acquiring all available. We analyzed sampling process developed...
Large-scale genomics has enabled proteomics by creating sequence infrastructures that can be used with mass spectrometry data to identify proteins. Although protein sequences deduced from nucleotide sequences, posttranslational modifications proteins, in general, cannot. We describe a process for the analysis of is simple, robust, and applied complicated mixtures. A or mixture digested using three different enzymes: one cleaves site-specific manner two others cleave nonspecifically. The...
Abstract As the speed with which proteomic labs generate data increases along scale of projects they are undertaking, resulting storage and processing problems will continue to challenge computational resources. This is especially true for shotgun techniques that can tens thousands spectra per instrument each day. One design factor leading many these caused by storing database identifications a given spectrum as individual files. While be addressed all search results in large relational...
Quantitative shotgun proteomic analyses are facilitated using chemical tags such as ICAT and metabolic labeling strategies with stable isotopes. The rapid high-throughput production of quantitative "shotgun" data necessitates the development software to automatically convert mass spectrometry-derived peptides into relative protein abundances. We describe a computer program called RelEx, which uses least-squares regression for calculation peptide ion current ratios from chromatograms. RelEx...
We report the results of our work to facilitate protein identification using tandem mass spectra and sequence databases. describe a parallel version SEQUEST (SEQUEST-PVM) that is tolerant toward arithmetic exceptions. The changes we effectively separate search processes on slave nodes from each other. Therefore, if one drops out cluster due an error, rest will carry process end. has been widely used for identifications. modifications made code improve its stability effectiveness in...
We present a new probability-based method for protein identification using tandem mass spectra and databases. The employs hypergeometric distribution to model frequencies of matches between fragment ions predicted peptide sequences with specific (M + H)+ value (at some tolerance) in sequence database an experimental spectrum. constitutes null hypothesis-all spectrum are random. It is used generate score characterizing the randomness match determine level significance hypothesis. For each...
The purpose of this work is to develop and verify statistical models for protein identification using peptide identifications derived from the results tandem mass spectral database searches. Recently we have presented a probabilistic model that uses hypergeometric distribution approximate fragment ion matches sequences experimental spectra. Here apply search validate identifications. For formulate problem in terms two independent models, two-hypothesis binomial multinomial which use...
We previously reported that the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (RSG) improved hippocampus-dependent cognition in Alzheimer's disease (AD) mouse model, Tg2576. RSG had no effect on wild-type littermate cognitive performance. Since extracellular signal-regulated protein kinase mitogen-activated (ERK MAPK) is required for many forms of learning and memory are affected AD, since both PPARγ ERK MAPK key mediators insulin signaling, current study tested...
Traditional proteomics provides static assessment of protein content, but not synthetic rates. Recently, proteome dynamics with heavy water ((2)H2O) was introduced, where (2)H labels amino acids that are incorporated into proteins, and the synthesis rate individual proteins is calculated using mass isotopomer distribution analysis. We refine this approach a novel algorithm rigorous selection criteria improve accuracy precision calculation rates use it to measure kinetics in spatially...
Nonalcoholic fatty liver disease (NAFLD) is associated with hepatic mitochondrial dysfunction characterized by reduced ATP synthesis. We applied the 2H2O-metabolic labeling approach to test hypothesis that stability of oxidative phosphorylation proteins contributes in a diet-induced mouse model NAFLD. A high fat diet containing cholesterol (a so-called Western (WD)) led stress, steatosis, inflammation and mild fibrosis, all markers NAFLD, low density (LDL) receptor deficient (LDLR−/−) mice....
We present an algorithmic approach to align three-dimensional chromatographic surfaces of LC-MS data complex mixture samples. The consists two steps. In the first step, we prealign profiles: two-dimensional projections surfaces. This is accomplished by correlation analysis using fast Fourier transforms. this a temporal offset that maximizes overlap and dot product between profiles determined. second algorithm generates matrix elements full mass scans reference sample from step indicates...
Metabolic labeling with heavy water followed by LC–MS is a high throughput approach to study proteostasis in vivo. Advances mass spectrometry and sample processing have allowed consistent detection of thousands proteins at multiple time points. However, freely available automated bioinformatics tools analyze extract protein decay rate constants are lacking. Here, we describe d2ome—a robust, software solution for vivo turnover analysis. d2ome highly scalable, uses innovative approaches...
We report the first determination of a “most” diabatic basis for triatomic molecule based exclusively on ab initio derivative couplings that takes careful account limitations imposed by nonremovable part those couplings. Baer [Chem. Phys. Lett. 35, 112 (1975)] showed an orthogonal transformation from adiabatic states to cannot remove all coupling unless curl vanishes. Subsequently, Mead and Truhlar [J. Chem. 77, 6090 (1982)] observed this does not, in general, vanish so some is nonremovable....
Hippocampal network hyperexcitability is considered an early indicator of Alzheimer's disease (AD) memory impairment. Some AD mouse models exhibit similar phenotypes. In this study we focused on dentate gyrus (DG) granule cell spontaneous and evoked properties in 9-month-old Tg2576 mice that model amyloidosis cognitive deficits. Using whole-cell patch-clamp recordings, found DG cells exhibited EPSCs were higher frequency but not amplitude compared with wild-type mice, suggesting...
Background Numerous metabolic pathways have been implicated in diabetes-induced renal injury, yet few studies utilized unbiased systems biology approaches for mapping the interconnectivity of diabetes-dysregulated proteins that are involved. We a global, quantitative, differential proteomic approach to identify novel retinoic acid hub cortical protein networks dysregulated by type 2 diabetes. Methodology/Principal Findings Total were extracted from cortex control and db/db mice at 20 weeks...
Understanding the pathologies related to regulation of protein metabolism requires methods for studying kinetics individual proteins. We developed a 2H2O metabolic labeling technique and software kinetic studies in free living organisms. This approach proteome dynamic measurement total body water enrichments by GC-MS, isotopic distribution tryptic peptide LC-MS/MS, estimation asymptotical number deuterium incorporated into software. applied this measure synthesis rates several plasma...
Tamoxifen (TMX) is a selective estrogen receptor modulator that can mimic the neuroprotective effects of but lacks its systemic adverse effects. We found TMX (1 mg/day) significantly improved motor recovery partially paralyzed hind limbs male adult rats with thoracic spinal cord injury (SCI), thus indicating translational potential for this cancer medication given clinical safety and applicability lack currently available treatments SCI. To shed light on mechanisms underlying beneficial SCI,...
Traumatic brain injury (TBI) is a complex and common problem resulting in the loss of cognitive function. In order to build comprehensive knowledge base proteins that underlie these deficits, we employed unbiased quantitative mass spectrometry, proteomics, bioinformatics identify quantify dysregulated CA3 subregion hippocampus fluid percussion model TBI rats. Using stable isotope 18O-water differential labeling multidimensional tandem liquid chromatography (LC)-MS/MS with high stringency...
We describe a stochastic model to compute in vivo protein turnover rate constants from stable-isotope labeling and high-throughput liquid chromatography-mass spectrometry experiments. show that the often-used one- two-compartment nonstochastic models allow explicit solutions corresponding differential equations. The resulting process is Gaussian processes with Ornstein-Uhlenbeck covariance matrix. applied large-scale data set (15)N compared its performance metrics those of curve fitting....