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Methionine Sulfoxide Speciation In Mouse Hippocampus Revealed By Global Proteomics Exhibits Age And Alzheimer’S Disease Dependent Changes Targeted To Mitochondrial And Glycolytic Pathways, Fillipa Blasco Tavares Pereira Lopes, Daniela Schlatzer, Mengzhen Li, Serhan Yılmaz, Rihua Wang, Xin Qi, Marzieh Ayati, Mehmet Koyutürk, Mark R. Chance

Computer Science Faculty Publications and Presentations

Methionine oxidation to the sulfoxide form (MSox) is a poorly understood post-translational modification of proteins associated with nonspecific chemical oxidation from reactive oxygen species (ROS) whose chemistries are linked to various disease pathologies including neurodegeneration. Emerging evidence shows MSox site occupancy is in some cases under enzymatic regulatory control mediating cellular signaling including phosphorylation and/or calcium signaling, raising questions as to the speciation and functional nature of MSox across the proteome. The 5XFAD lineage of the C57BL/6 mouse has well-defined Alzheimer’s and aging states. Using this model, we analyzed age, sex and disease dependent MSox speciation in mouse hippocampus. In …

Analysis Of Post-Translational Modifications (Ptm) Crosstalk, Amit Das

Theses and Dissertations

Mass spectrometry-based proteomics is a powerful tool for identifying post-translational modifications (PTMs) across the proteome. O-GlcNAcylation and phosphorylation are two PTMs that play crucial roles in regulating cellular processes, including cardiac contractile function. Dysregulation of these PTMs has been implicated in the development and progression of diabetic cardiomyopathy. In this study, we aimed to investigate the interplay between O-GlcNAcylation and phosphorylation in healthy and type 2 diabetic hearts, with a specific focus on the functional relationships between these PTMs and their potential therapeutic implications.

Utilizing mass spectrometry data, we identified and quantified specific PTMs on myofilament proteins, uncovering 1354 O-GlcNAcylated …

Ensemble Protein Inference Evaluation, Kyle Lee Lucke

Graduate Student Theses, Dissertations, & Professional Papers

The Protein inference problem is becoming an increasingly important tool that aids in the characterization of complex proteomes and analysis of complex protein samples. In bottom-up shotgun proteomics experiments the metrics for evaluation (like AUC and calibration error) are based on an often imperfect target-decoy database. These metrics make the inherent assumption that all of the proteins in the target set are present in the sample being analyzed. In general, this is not the case, they are typically a mix of present and absent proteins. To objectively evaluate inference methods, protein standard datasets are used. These datasets are special in …

High-Performance Reductive Strategies For Big Data From Lc-Ms/Ms Proteomics, Muaaz Gul Awan

Dissertations

Mass Spectrometry (MS)-based proteomics utilizes high performance liquid chromatography in tandem with high-throughput mass spectrometers. These experiments can produce MS data sets with astonishing speed and volume that can easily reach peta-scale level, creating storage and computational problems for large-scale systems biology studies. Each spectrum output by a mass spectrometer may consist of thousands of peaks, which must all be processed to deduce the corresponding peptide. However, only a small percentage of peaks in a spectrum are useful for further processing, as most of the peaks are either noise or are not useful. Our experiments have shown that 90 to …

A Holistic Computational Approach To Boosting The Performance Of Protein Search Engines, Majdi Ahmad Mosa Maabreh

Dissertations

Despite availability of several proteins search engines, due to the increasing amounts of MS/MS data and database sizes, more efficient data analysis and reduction methods are important. Improving accuracy and performance of protein identification is a main goal in the community of proteomic research. In this research, a holistic solution for improvement in search performance is developed.

Most current search engines apply the SEQUEST style of searching protein databases to define MS/MS spectra. SEQUEST involves three main phases: (i) Indexing the protein databases, (ii) Matching and Ranking the MS/MS spectra and (iii) Filtering the matches and reporting the final proteins. …

Nbpmf: Novel Network-Based Inference Methods For Peptide Mass Fingerprinting, Zhewei Liang

Electronic Thesis and Dissertation Repository

Proteins are large, complex molecules that perform a vast array of functions in every living cell. A proteome is a set of proteins produced in an organism, and proteomics is the large-scale study of proteomes. Several high-throughput technologies have been developed in proteomics, where the most commonly applied are mass spectrometry (MS) based approaches. MS is an analytical technique for determining the composition of a sample. Recently it has become a primary tool for protein identification, quantification, and post translational modification (PTM) characterization in proteomics research. There are usually two different ways to identify proteins: top-down and bottom-up. Top-down approaches …

Recent Advances In Clustering Methods For Protein Interaction Networks, Jianxin Wang, Min Li, Youping Deng, Yi Pan

Computer Science Faculty Publications

The increasing availability of large-scale protein-protein interaction data has made it possible to understand the basic components and organization of cell machinery from the network level. The arising challenge is how to analyze such complex interacting data to reveal the principles of cellular organization, processes and functions. Many studies have shown that clustering protein interaction network is an effective approach for identifying protein complexes or functional modules, which has become a major research topic in systems biology. In this review, recent advances in clustering methods for protein interaction networks will be presented in detail. The predictions of protein functions and …

Statistical Issues In Proteomic Research, Jeffrey S. Morris

Jeffrey S. Morris

No abstract provided.

Analysis Of Mass Spectrometry Data Using Bayesian Wavelet-Based Functional Mixed Models, Jeffrey S. Morris, Philip J. Brown, Keith A. Baggerly, Kevin R. Coombes

Jeffrey S. Morris

In this chapter, we demonstrate how to analyze MALDI-TOF/SELDITOF mass spectrometry data using the wavelet-based functional mixed model introduced by Morris and Carroll (2006), which generalizes the linear mixed models to the case of functional data. This approach models each spectrum as a function, and is very general, accommodating a broad class of experimental designs and allowing one to model nonparametric functional effects for various factors, which can be conditions of interest (e.g. cancer/normal) or experimental factors (blocking factors). Inference on these functional effects allows us to identify protein peaks related to various outcomes of interest, including dichotomous outcomes, categorical …

Improved Peak Detection And Quantification Of Mass Spectrometry Data Acquired From Surface-Enhanced Laser Desorption And Ionization By Denoising Spectra With The Undecimated Discrete Wavelet Transform, Kevin R. Coombes, Spiros Tsavachidis, Jeffrey S. Morris, Keith A. Baggerly, Henry M. Kuerer

Jeffrey S. Morris

Background: Mass spectrometry, especially surface enhanced laser desorption and ionization (SELDI) is increasingly being used to find disease-related proteomic patterns in complex mixtures of proteins derived from tissue samples or from easily obtained biological fluids such as serum, urine, or nipple aspirate fluid. Questions have been raised about the reproducibility and reliability of peak quantifications using this technology. For example, Yasui and colleagues opted to replace continuous measures of the size of a peak by a simple binary indicator of its presence or absence in their analysis of a set of spectra from prostate cancer patients.

Methods: We collected nipple …

Proteome Database Of Hepatocellular Carcinoma., Cynthia Liang, Jason Neo, Siaw Ling Lo, Gek San Tan, Teck Keong Seow, Maxey Chung

Research Collection School Of Computing and Information Systems

Hepatocellular carcinoma (HCC or hepatoma) is the most common primary cancer of the liver. Persistent viral infection by the hepatic B or C virus is probably the most important cause of HCC worldwide. It is responsible for approximately one million deaths each year, predominantly in the underdeveloped and developing countries, but its incidence is also on the rise in the developed countries. For most patients suffering from HCC, long-term survival is rare, as they are presented late and are often unsuitable for curative treatment. Thus there is great interest to identify novel HCC diagnostic markers for early detection of the …