scholarly journals A Peptidoform Matching Strategy in Bottom-Up Proteomics for Studying Functions of Post-Translational Modifications

2021 ◽  
Author(s):  
Yansheng Liu
Keyword(s):  
Quantitative Analysis ◽  
Relevant Information ◽  
Previous Literature ◽  
Biological Functions ◽  
Biological Investigation ◽  
Bottom Up ◽  
Post Translational Modifications ◽  
Site Specific ◽  
Specific Approach ◽  
Matching Strategy

Protein translational modifications (PTMs) generate an enormous, but as yet undetermined, expansion of the expressed proteoforms. In this Viewpoint, we firstly differentiate the concepts of proteoform and peptidoform by reviewing and discussing previous literature. We show that the current PTM biological investigation and annotation largely follow a PTM site-specific rather than proteoform-specific approach. We further illustrate a potentially useful matching strategy in which a particular “modified peptidoform” is matched to the corresponding “unmodified peptidoform” as a reference for the quantitative analysis between samples and conditions. We suggest this strategy could provide directly relevant information for learning the PTM site-specific biological functions. Accordingly, we advocate for the wider use of the nomenclature “peptidoform” in the future bottom-up proteomic studies.

scholarly journals Quantifying homologous proteins and proteoforms

2017 ◽  
Author(s):  
Dmitry Malioutov ◽  
Tianchi Chen ◽  
Jacob Jaffe ◽  
Edoardo Airoldi ◽  
Steve Carr ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Alternative Splicing ◽  
Histone Modification ◽  
First Principles ◽  
High Accuracy ◽  
Biological Functions ◽  
Homologous Proteins ◽  
Bottom Up ◽  
Post Translational Modifications ◽  
Paralogous Genes

Many proteoforms – arising from alternative splicing, post-translational modifications (PTMs), or paralogous genes – have distinct biological functions, such as histone PTM proteoforms. However, their quantification by existing bottom-up mass–spectrometry (MS) methods is undermined by peptide-specific biases. To avoid these biases, we developed and implemented a first-principles model (HIquant) for quantifying proteoform stoichiometries. We characterized when MS data allow inferring proteoform stoichiometries by HIquant, derived an algorithm for optimal inference, and demonstrated experimentally high accuracy in quantifying fractional PTM occupancy without using external standards, even in the challenging case of the histone modification code. A HIquant server is implemented at: https://web.northeastern.edu/slavov/2014_HIquant/

The challenge of detecting modifications on proteins

2020 ◽  
Vol 64 (1) ◽  
pp. 135-153 ◽  
Author(s):  
Lauren Elizabeth Smith ◽  
Adelina Rogowska-Wrzesinska
Keyword(s):  
Mass Spectrometry ◽  
Protein Function ◽  
Chemical Properties ◽  
Lysine Acetylation ◽  
Mass Determination ◽  
Post Translational Modifications ◽  
Site Specific ◽  
The Common

Abstract Post-translational modifications (PTMs) are integral to the regulation of protein function, characterising their role in this process is vital to understanding how cells work in both healthy and diseased states. Mass spectrometry (MS) facilitates the mass determination and sequencing of peptides, and thereby also the detection of site-specific PTMs. However, numerous challenges in this field continue to persist. The diverse chemical properties, low abundance, labile nature and instability of many PTMs, in combination with the more practical issues of compatibility with MS and bioinformatics challenges, contribute to the arduous nature of their analysis. In this review, we present an overview of the established MS-based approaches for analysing PTMs and the common complications associated with their investigation, including examples of specific challenges focusing on phosphorylation, lysine acetylation and redox modifications.

Developing Ambient Water Quality Criteria for Mercury: A Probabilistic Site-Specific Approach

2015 ◽  
Vol 2 (0) ◽  
pp. 9781780404028-9781780404028
Author(s):  
D. R. J. Moore ◽  
A. Pawlisz ◽  
R. Scott Teed
Keyword(s):  
Water Quality ◽  
Quality Criteria ◽  
Water Quality Criteria ◽  
Ambient Water ◽  
Site Specific ◽  
Specific Approach

scholarly journals Novel Roles for the Sirtuin Deacylase SIRT5 in Normal Physiology and in Cancer

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 741-741
Author(s):  
David Lombard
Keyword(s):  
Mitochondrial Matrix ◽  
Genomic Integrity ◽  
Biological Functions ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Catalytic Activities ◽  
Cellular Processes ◽  
Specific Cancer ◽  
Cancer Types ◽  
Chromatin Biology

Abstract Sirtuins are NAD+-dependent deacylases that regulate diverse cellular processes such as metabolic homeostasis and genomic integrity. Mammals possess seven sirtuin family members, SIRT1-SIRT7, that display diverse subcellular localization patterns, catalytic activities, protein targets, and biological functions. Three sirtuins, SIRT3, SIRT4, and SIRT5, are primarily located in the mitochondrial matrix. SIRT5 is a very inefficient deacetylase, instead removing negatively charged post-translational modifications (succinyl, glutaryl, and malonyl groups) from lysines of its target proteins, in mitochondria and throughout the cell. SIRT5 plays only modest known roles in normal physiology, with its major functions occurring in the heart under stress conditions. In contrast, in specific cancer types, including melanoma, we have identified a major pro-survival role for SIRT5. We have traced this function of SIRT5 to novel roles for this protein in regulating chromatin biology. New insights into mechanisms of SIRT5 action in cancer, and in normal myocardium, will be discussed.

scholarly journals Phosphorylation of the Regulators, a Complex Facet of NF-κB Signaling in Cancer

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 15
Author(s):  
Aishat Motolani ◽  
Matthew Martin ◽  
Mengyao Sun ◽  
Tao Lu
Keyword(s):  
Transcription Factor ◽  
Cardiovascular Diseases ◽  
Cancer Progression ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Malignant Diseases ◽  
Future Perspectives ◽  
Post Translational Modifications ◽  
Site Specific

The nuclear factor kappa B (NF-κB) is a ubiquitous transcription factor central to inflammation and various malignant diseases in humans. The regulation of NF-κB can be influenced by a myriad of post-translational modifications (PTMs), including phosphorylation, one of the most popular PTM formats in NF-κB signaling. The regulation by phosphorylation modification is not limited to NF-κB subunits, but it also encompasses the diverse regulators of NF-κB signaling. The differential site-specific phosphorylation of NF-κB itself or some NF-κB regulators can result in dysregulated NF-κB signaling, often culminating in events that induce cancer progression and other hyper NF-κB related diseases, such as inflammation, cardiovascular diseases, diabetes, as well as neurodegenerative diseases, etc. In this review, we discuss the regulatory role of phosphorylation in NF-κB signaling and the mechanisms through which they aid cancer progression. Additionally, we highlight some of the known and novel NF-κB regulators that are frequently subjected to phosphorylation. Finally, we provide some future perspectives in terms of drug development to target kinases that regulate NF-κB signaling for cancer therapeutic purposes.

Site-specific Quantitative Analysis of Overglycosylation of Collagen in Osteogenesis Imperfecta Using Hydrazide Chemistry and SILAC

2013 ◽  
Vol 12 (5) ◽  
pp. 2225-2232 ◽  
Author(s):  
Yuki Taga ◽  
Masashi Kusubata ◽  
Kiyoko Ogawa-Goto ◽  
Shunji Hattori
Keyword(s):  
Quantitative Analysis ◽  
Osteogenesis Imperfecta ◽  
Site Specific

scholarly journals VectorMOD: Method for Bottom-Up Proteomic Characterization of rAAV Capsid Post-Translational Modifications and Vector Impurities

2021 ◽  
Vol 12 ◽  
Author(s):  
Neil G. Rumachik ◽  
Stacy A. Malaker ◽  
Nicole K. Paulk
Keyword(s):  
Mass Spectrometry ◽  
Process Development ◽  
Cell Protein ◽  
Macromolecular Complex ◽  
Bottom Up ◽  
Post Translational Modifications ◽  
Simple Step ◽  
Product And Process ◽  
High Doses ◽  
And Control

Progress in recombinant AAV gene therapy product and process development has advanced our understanding of the basic biology of this critical delivery vector. The discovery of rAAV capsid post-translational modifications (PTMs) has spurred interest in the field for detailed rAAV-specific methods for vector lot characterization by mass spectrometry given the unique challenges presented by this viral macromolecular complex. Recent concerns regarding immunogenic responses to systemically administered rAAV at high doses has highlighted the need for investigators to catalog and track potentially immunogenic vector lot components including capsid PTMs and PTMs on host cell protein impurities. Here we present a simple step-by-step guide for academic rAAV laboratories and Chemistry, Manufacturing and Control (CMC) groups in industry to perform an in-house or outsourced bottom-up mass spectrometry workflow to characterize capsid PTMs and process impurities.

scholarly journals Reevaluating the Influence of Leaders Under Proportional Representation: Quantitative Analysis of Text in an Electoral Experiment

2021 ◽  
Vol 12 ◽  
Author(s):  
Annika Fredén ◽  
Sverker Sikström
Keyword(s):  
Statistical Analysis ◽  
Quantitative Analysis ◽  
Statistical Models ◽  
Proportional Representation ◽  
Previous Literature ◽  
Vote Choice ◽  
Election Campaigns ◽  
Similar Extent ◽  
Text Data ◽  
Representation Systems

We propose that leaders play a more important role in voters’ party sympathy in proportional representation systems (PR) than previous research has suggested. Voters, from the 2018 Swedish General Election, were in an experiment asked to describe leaders and parties with three indicative keywords. Statistical models were conducted on these text data to predict their vote choice. The results show that despite that the voters vote for a party, the descriptions of leaders predicted vote choice to a similar extent as descriptions of parties. However, the order of the questions mattered, so that the first questions were more predictive than the second question. These analyses indicate that voters tend to conflate characteristics of leaders with their parties during election campaigns, and that leaders are a more important aspect of voting under PR than previous literature has suggested. Overall, this suggests that statistical analysis of words sheds new light of underlying sympathies related to voting.

scholarly journals pGlycoQuant with a deep residual network for precise and minuscule-missing-value quantitative glycoproteomics enabling the functional exploration of site-specific glycosylation

2021 ◽  
Author(s):  
Weiqian Cao ◽  
Siyuan Kong ◽  
Wenfeng Zeng ◽  
Pengyun Gong ◽  
Biyun Jiang ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Large Scale ◽  
Missing Values ◽  
Software Tool ◽  
Software Tools ◽  
Residual Network ◽  
Site Specific ◽  
Carcinoma Cell Lines ◽  
L1 Cell Adhesion Molecule

Interpreting large-scale glycoproteomic data for intact glycopeptide identification has been tremendously advanced by software tools. However, software tools for quantitative analysis of intact glycopeptides remain lagging behind, which greatly hinders exploring the differential expression and functions of site-specific glycosylation in organisms. Here, we report pGlycoQuant, a generic software tool for accurate and convenient quantitative intact glycopeptide analysis, supporting both primary and tandem mass spectrometry quantitation for multiple quantitative strategies. pGlycoQuant enables intact glycopeptide quantitation with very low missing values via a deep residual network, thus greatly expanding the quantitative function of several powerful search engines, currently including pGlyco 2.0, pGlyco3, Byonic and MSFragger-Glyco. The pGlycoQuant-based site-specific N-glycoproteomic study conducted here quantifies 6435 intact N-glycopeptides in three hepatocellular carcinoma cell lines with different metastatic potentials and, together with in vitro molecular biology experiments, illustrates core fucosylation at site 979 of the L1 cell adhesion molecule (L1CAM) as a potential regulator of HCC metastasis. pGlycoQuant is freely available at https://github.com/expellir-arma/pGlycoQuant/releases/. We have demonstrated pGlycoQuant to be a powerful tool for the quantitative analysis of site-specific glycosylation and the exploration of potential glycosylation-related biomarker candidates, and we expect further applications in glycoproteomic studies.

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