Bioinformatics of High Throughput Proteomics Using Tandem Mass Spectrometry of Intact Proteins PDF Download
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Author: Richard D. LeDuc
Publisher: ProQuest
ISBN: 9780549340737
Category :
Languages : en
Pages : 143
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Book Description
Top down mass spectrometry is a unique approach to the problem of identifying and characterizing proteins with a DNA-predicted sequence. It would be desirable to move top down mass spectrometry in to the 'omic' sciences by developing a high throughput form that could be used to simultaneously identify and characterize thousands of proteins. Before this is possible, the bioinformatic analysis of top down mass spectrometric data needed to be automated. This work demonstrates a functional automated top down search environment called ProSightHT. Further, it derives and demonstrates the utility of an improved scoring system that simultaneously reduces the rate of false identifications and missed characterizations. A superior Automated Protein Characterization database schema is introduced that allows the storage of all prior protein form information, and a statistically valid approach to protein form quantification is demonstrated.
Author: Richard D. LeDuc
Publisher: ProQuest
ISBN: 9780549340737
Category :
Languages : en
Pages : 143
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Book Description
Top down mass spectrometry is a unique approach to the problem of identifying and characterizing proteins with a DNA-predicted sequence. It would be desirable to move top down mass spectrometry in to the 'omic' sciences by developing a high throughput form that could be used to simultaneously identify and characterize thousands of proteins. Before this is possible, the bioinformatic analysis of top down mass spectrometric data needed to be automated. This work demonstrates a functional automated top down search environment called ProSightHT. Further, it derives and demonstrates the utility of an improved scoring system that simultaneously reduces the rate of false identifications and missed characterizations. A superior Automated Protein Characterization database schema is introduced that allows the storage of all prior protein form information, and a statistically valid approach to protein form quantification is demonstrated.
Author: Timothy D. Veenstra
Publisher: John Wiley & Sons
ISBN: 1119081726
Category : Science
Languages : en
Pages : 408
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Book Description
An update to the popular guide to proteomics technology applications in biomedical research Building on the strength of the original edition, this book presents the state of the art in the field of proteomics and offers students and scientists new tools and techniques to advance their own research. Written by leading experts in the field, it provides readers with an understanding of new and emerging directions for proteomics research and applications. Proteomics for Biological Discovery begins by discussing the emergence of proteomics technologies and summarizing the potential insights to be gained from proteome-level research. The tools of proteomics, from conventional to novel techniques, are thoroughly covered, from underlying concepts to limitations and future directions. Later chapters provide an overview of the current developments in post-translational modification studies, structural proteomics, biochemical proteomics, applied proteomics, and bioinformatics relevant to proteomics. Chapters cover: Quantitative Proteomics for Differential Protein Expression Profiling; Protein Microarrays; Protein Biomarker Discovery; Biomarker Discovery using Mass Spectrometry Imaging; Protein-Protein Interactions; Mass Spectrometry Of Intact Protein Complexes; Crosslinking Applications in Structural Proteomics; Functional Proteomics; High Resolution Interrogation of Biological Systems via Mass Cytometry; Characterization of Drug-Protein Interactions by Chemoproteomics; Phosphorylation; Large-Scale Phosphoproteomics; and Probing Glycoforms of Individual Proteins Using Antibody-Lectin Sandwich Arrays. Presents a comprehensive and coherent review of the major issues in proteomic technology development, bioinformatics, strategic approaches, and applications Chapters offer a rigorous overview with summary of limitations, emerging approaches, questions, and realistic future industry and basic science applications Features new coverage of mass spectrometry for high throughput proteomic measurements, and novel quantitation strategies such as spectral counting and stable isotope labeling Discusses higher level integrative aspects, including technical challenges and applications for drug discovery Offers new chapters on biomarker discovery, global phosphorylation analysis, proteomic profiling using antibodies, and single cell mass spectrometry Proteomics for Biological Discovery is an excellent advanced resource for graduate students, postdoctoral fellows, and scientists across all the major fields of biomedical science.
Author: Timothy Palzkill
Publisher: Springer Science & Business Media
ISBN: 0306468956
Category : Science
Languages : en
Pages : 128
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Book Description
Proteomics is an introduction to the exciting new field of proteomics, an interdisciplinary science that includes biology, bioinformatics, and protein chemistry. The purpose of this book is to provide the active researcher with an overview of the types of questions being addressed in proteomics studies and the technologies used to address those questions. Key subjects covered in this book include: an assessment of the limitations of this approach and outlines new developments in mass spectrometry that will advance future research high-throughput recombinant DNA cloning methods used to systematically clone all of the open reading frames of an organism into plasmid vectors for large scale protein expression and functional studies such as protein-protein interactions with the two-hybrid system protein structure an overview of large-scale experimental attempts to determine the three-dimensional structures of representative sets of proteins computational approaches to determining the three-dimensional structure of proteins. Proteomics provides a starting point for researchers who would like a theoretical understanding of the new technologies in the field, and obtain a solid grasp of the fundamentals before integrating new tools into their experiments. Written with attention to detail, but without being overwhelmingly technical, Proteomics is a user-friendly guide needed by most biologists today.
Author: Conrad Bessant
Publisher: Royal Society of Chemistry
ISBN: 1782626735
Category : Science
Languages : en
Pages : 429
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Book Description
The field of proteomics has developed rapidly over the past decade nurturing the need for a detailed introduction to the various informatics topics that underpin the main liquid chromatography tandem mass spectrometry (LC-MS/MS) protocols used for protein identification and quantitation. Proteins are a key component of any biological system, and monitoring proteins using LC-MS/MS proteomics is becoming commonplace in a wide range of biological research areas. However, many researchers treat proteomics software tools as a black box, drawing conclusions from the output of such tools without considering the nuances and limitations of the algorithms on which such software is based. This book seeks to address this situation by bringing together world experts to provide clear explanations of the key algorithms, workflows and analysis frameworks, so that users of proteomics data can be confident that they are using appropriate tools in suitable ways.
Author: Timothy D. Veenstra
Publisher: John Wiley & Sons
ISBN: 0470007737
Category : Science
Languages : en
Pages : 361
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Book Description
Written by recognized experts in the study of proteins, Proteomics for Biological Discovery begins by discussing the emergence of proteomics from genome sequencing projects and a summary of potential answers to be gained from proteome-level research. The tools of proteomics, from conventional to novel techniques, are then dealt with in terms of underlying concepts, limitations and future directions. An invaluable source of information, this title also provides a thorough overview of the current developments in post-translational modification studies, structural proteomics, biochemical proteomics, microfabrication, applied proteomics, and bioinformatics relevant to proteomics. Presents a comprehensive and coherent review of the major issues faced in terms of technology development, bioinformatics, strategic approaches, and applications Chapters offer a rigorous overview with summary of limitations, emerging approaches, questions, and realistic future industry and basic science applications Discusses higher level integrative aspects, including technical challenges and applications for drug discovery Accessible to the novice while providing experienced investigators essential information Proteomics for Biological Discovery is an essential resource for students, postdoctoral fellows, and researchers across all fields of biomedical research, including biochemistry, protein chemistry, molecular genetics, cell/developmental biology, and bioinformatics.
Author: Rune Matthiesen
Publisher: Springer Science & Business Media
ISBN: 1597452750
Category : Science
Languages : en
Pages : 322
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Book Description
This is an in-depth guide to the theory and practice of analyzing raw mass spectrometry (MS) data in proteomics. The volume outlines available bioinformatics programs, algorithms, and databases available for MS data analysis. General guidelines for data analysis using search engines such as Mascot, Xtandem, and VEMS are provided, with specific attention to identifying poor quality data and optimizing search parameters.
Author: Gabriel Waksman
Publisher: Springer Science & Business Media
ISBN: 0387245324
Category : Medical
Languages : en
Pages : 325
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Book Description
Gabriel Waksman Institute of Structural Molecular Biology, Birkbeck and University College London, Malet Street, London WC1E 7HX, United Kingdom Address for correspondence: Professor Gabriel Waksman Institute of Structural Molecular Biology Birkbeck and University College London Malet Street London WC1E 7H United Kingdom Email: g. waksman@bbk. ac. uk and g. waksman@ucl. ac. uk Phone: (+44) (0) 207 631 6833 Fax: (+44) (0) 207 631 6833 URL: http://people. cryst. bbk. ac. uk/?ubcg54a Gabriel Waksman is Professor of Structural Molecular Biology at the Institute of Structural Molecular Biology at UCL/Birkbeck, of which he is also the director. Before joining the faculty of UCL and Birkbeck, he was the Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics at the Washington University School of Medicine in St Louis (USA). The rapidly evolving ?eld of protein science has now come to realize the ubiquity and importance of protein–protein interactions. It had been known for some time that proteins may interact with each other to form functional complexes, but it was thought to be the property of only a handful of key proteins. However, with the advent of hi- throughput proteomics to monitor protein–protein interactions at an organism level, we can now safely state that protein–protein interactions are the norm and not the exception.
Author: Ari Michael Frank
Publisher:
ISBN:
Category :
Languages : en
Pages : 205
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Book Description
Tandem mass spectrometry (MS/MS) has emerged as the leading technology for high-throughput proteomics analysis, making it possible to rapidly identify and characterize thousands of different proteins in complex biological samples. In recent years we have witnessed a dramatic increase in the capability to acquire proteomics MS/MS data. To avoid computational bottlenecks, this growth in acquisition power must be accompanied by a comparable improvement in analysis capabilities. In this dissertation we present several algorithms we developed to meet some of the major computational challenges that have arisen in MS/MS analysis. Throughout our work we continually address two (sometimes overlapping) problems: how to make MS/MS-based sequence identifications more accurate, and how to make the identification process work much faster. Much of the work we present revolves around algorithms for de novo sequencing of peptides, which aims to discover the amino acid sequence of protein digests (peptides), solely from their experimental mass spectrum. We start off by describing a new scoring model which is used in our de novo sequencing algorithm called PepNovo. Our scoring scheme is based on a graphical model decomposition that describes many of the conditions that determine the intensities of fragment ions observed in mass spectra, such as dependencies between related fragment ions and the influence of the amino acids adjacent to the cleavage site. Besides predicting whole peptide sequences, one of the most useful applications of de novo algorithms is to generate short sequence tags for the purpose of database filtration. We demonstrate how using these tags speeds up database searches by two orders of magnitude compared to conventional methods. We extend the use of tag filtration and show that with high-resolution data, our de novo sequencing is accurate enough to enable extremely rapid identification via direct hash lookup of peptide sequences. The vast amount of MS/MS data that has become available has made it possible to use advanced data-driven machine learning methods to devise more acute algorithms. We describe a new scoring function for peptide-spectrum matches that uses the RankBoost ranking algorithm to learn and model the influences of the many intricate processes that occur during peptide fragmentation. Our method's superior discriminatory power boosts PepNovo's performance beyond the current state-of-the-art de novo sequencing algorithms. Our score also greatly improves the performance of database search programs, significantly increasing both their speed and sensitivity. When we applied our method to the challenging task of a proteogenomic search against a six-frame translation of the human genome, we were able to significantly increase the number of peptide identifications compared to current techniques by 60\%. To help speed up MS/MS analysis, we developed a clustering algorithm that exploits the redundancy that is inherent in large mass spectrometry datasets (these often contain hundreds and even thousands of spectra of the same peptide). When applied to large MS/MS datasets on the order of ten million spectra, our clustering algorithm reduces the number of spectra by an order of magnitude, without losing peptide identifications. Finally, we touch upon sequencing of intact proteins (``top-down'' analysis), which from a computational perspective, is only in its infancy -- very few algorithms have been developed for analysis of this type of data. We developed MS-TopDown, which uses the Spectral Alignment algorithm to characterize protein forms (i.e., determine the modification/mutation sites). Our algorithm can handle heavily modified proteins and can also distinguish between several isobaric protein forms present in the same spectrum.
Author: Timothy D. Veenstra
Publisher: Academic Press
ISBN: 0080569153
Category : Science
Languages : en
Pages : 445
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Book Description
The content of this volume is designed to reach a wide audience, including those involved with relevant technologies such as electrophoresis and mass spectrometry, to those interested in how proteomics can benefit research. A wide range of techniques are discussed, each specifically designed to address different needs in proteomic analysis. The concluding chapter discusses the important issue related to handling large amounts of data accumulated in proteomic studies. - Discusses proteomics in the postgenomic age - Includes various strategies for quantitative proteomics - Covers the role of MS in structural functional proteomics and proteomics in drug discovery and bioinformatics
Author: Gary Siuzdak
Publisher:
ISBN: 9780974245126
Category : Bioengineering
Languages : en
Pages : 0
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Book Description
Covers the basic concepts in mass spectrometry as well as advanced topics including protein identification/protein structural analysis, carbohydrate and oligonucleotide analysis. Topics also include pharmacokinetics, high throughput screening, and the recent development of mass spectrometry in clinical diagnosis.
