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Methods in Molecular Biology (Clifton,... 2022A fundamental goal of systems biology is to seek a better understanding of the cell's molecular mechanisms. Experimentalists most frequently rely upon reductionist...
A fundamental goal of systems biology is to seek a better understanding of the cell's molecular mechanisms. Experimentalists most frequently rely upon reductionist methods to isolate and analyze discrete signaling compartments, including subcellular domains, organelles, and protein-protein interactions. Among the systems-biology community, there is a growing need to integrate multiple datasets to resolve complex cellular networks. In this chapter, we share our procedures for the discovery of integrated signaling networks, across multi-proteomic data. Demonstrating these procedures, we provide an integrated analysis of the cellular proteome and extracellular (secretome) of human glioma LN229.
Topics: Humans; Proteome; Proteomics; Systems Biology
PubMed: 35612742
DOI: 10.1007/978-1-0716-2124-0_12 -
Expert Review of Proteomics Feb 2021The goal of this review is to highlight the triumphs and frontiers in measurement of the lens proteome as it relates to onset of age-related nuclear cataract. As global... (Review)
Review
INTRODUCTION
The goal of this review is to highlight the triumphs and frontiers in measurement of the lens proteome as it relates to onset of age-related nuclear cataract. As global life expectancy increases, so too does the frequency of age-related nuclear cataracts. Molecular therapeutics do not exist for delay or relief of cataract onset in humans. Since lens fiber cells are incapable of protein synthesis after initial maturation, age-related changes in proteome composition and post-translational modification accumulation can be measured with various techniques. Several of these modifications have been associated with cataract onset.
AREAS COVERED
We discuss the impact of long-lived proteins on the lens proteome and lens homeostasis as well as proteomic techniques that may be used to measure proteomes at various levels of proteomic specificity and spatial resolution.
EXPERT OPINION
There is clear evidence that several proteome modifications are correlated with cataract formation. Past studies should be enhanced with cutting-edge, spatially resolved mass spectrometry techniques to enhance the specificity and sensitivity of modification detection as it relates to cataract formation.
Topics: Cataract; Humans; Lens, Crystalline; Mass Spectrometry; Proteome; Proteomics
PubMed: 33849365
DOI: 10.1080/14789450.2021.1913062 -
Expert Review of Proteomics Mar 2022Due to its excellent sensitivity, nano-flow liquid chromatography tandem mass spectrometry (LC-MS/MS) is the mainstay in proteome research; however, this comes at the... (Review)
Review
INTRODUCTION
Due to its excellent sensitivity, nano-flow liquid chromatography tandem mass spectrometry (LC-MS/MS) is the mainstay in proteome research; however, this comes at the expense of limited throughput and robustness. In contrast, micro-flow LC-MS/MS enables high-throughput, robustness, quantitative reproducibility, and precision while retaining a moderate degree of sensitivity. Such features make it an attractive technology for a wide range of proteomic applications. In particular, large-scale projects involving the analysis of hundreds to thousands of samples.
AREAS COVERED
This review summarizes the history of chromatographic separation in discovery proteomics with a focus on micro-flow LC-MS/MS, discusses the current state-of-the-art, highlights advances in column development and instrumentation, and provides guidance on which LC flow best supports different types of proteomic applications.
EXPERT OPINION
Micro-flow LC-MS/MS will replace nano-flow LC-MS/MS in many proteomic applications, particularly when sample quantities are not limited and sample cohorts are large. Examples include clinical analyses of body fluids, tissues, drug discovery and chemical biology investigations, plus systems biology projects across all kingdoms of life. When combined with rapid and sensitive MS, intelligent data acquisition, and informatics approaches, it will soon become possible to analyze large cohorts of more than 10,000 samples in a comprehensive and fully quantitative fashion.
Topics: Humans; Chromatography, Liquid; Proteomics; Proteome; Tandem Mass Spectrometry; Reproducibility of Results
PubMed: 36221222
DOI: 10.1080/14789450.2022.2134780 -
Platelets Dec 2023Proteomics tools provide a powerful means to identify, detect, and quantify protein-related details in studies of platelet phenotype and function. Here, we consider how...
Proteomics tools provide a powerful means to identify, detect, and quantify protein-related details in studies of platelet phenotype and function. Here, we consider how historical and recent advances in proteomics approaches have informed our understanding of platelet biology, and, how proteomics tools can be used going forward to advance studies of platelets. It is now apparent that the platelet proteome is comprised of thousands of different proteins, where specific changes in platelet protein systems can accompany alterations in platelet function in health and disease. Going forward, many challenges remain in how to best carry out, validate and interpret platelet proteomics experiments. Future studies of platelet protein post-translational modifications such as glycosylation, or studies that take advantage of single cell proteomics and top-down proteomics methods all represent areas of interest to profiling and more richly understanding platelets in human wellness and disease.
Topics: Humans; Blood Platelets; Proteomics; Phenotype; Proteome
PubMed: 37246523
DOI: 10.1080/09537104.2023.2217932 -
International Journal of Molecular... Feb 2024The liver is the central metabolic organ and produces 85-90% of the proteins found in plasma. Accordingly, the plasma proteome is an attractive source of liver disease... (Review)
Review
The liver is the central metabolic organ and produces 85-90% of the proteins found in plasma. Accordingly, the plasma proteome is an attractive source of liver disease biomarkers that reflects the different cell types present in this organ, as well as the processes such as responses to acute and chronic injury or the formation of an extracellular matrix. In the first part, we summarize the biomarkers routinely used in clinical evaluations and their biological relevance in the different stages of non-malignant liver disease. Later, we describe the current proteomic approaches, including mass spectrometry and affinity-based techniques, that allow a more comprehensive assessment of the liver function but also require complex data processing. The many approaches of analysis and interpretation and their potential caveats are delineated. While these advances hold the promise to transform our understanding of liver diseases and support the development and validation of new liver-related drugs, an interdisciplinary collaboration is needed.
Topics: Humans; Proteome; Proteomics; Biomarkers; Liver Diseases
PubMed: 38396688
DOI: 10.3390/ijms25042008 -
Biochemistry. Biokhimiia Sep 2022Chemical proteomics, emerging rapidly in recent years, has become a main approach to identifying interactions between the small molecules and proteins in the cells on a... (Review)
Review
Chemical proteomics, emerging rapidly in recent years, has become a main approach to identifying interactions between the small molecules and proteins in the cells on a proteome scale and mapping the signaling and/or metabolic pathways activated and regulated by these interactions. The methods of chemical proteomics allow not only identifying proteins targeted by drugs, characterizing their toxicity and discovering possible off-target proteins, but also elucidation of the fundamental mechanisms of cell functioning under conditions of drug exposure or due to the changes in physiological state of the organism itself. Solving these problems is essential for both basic research in biology and clinical practice, including approaches to early diagnosis of various forms of serious diseases or prediction of the effectiveness of therapeutic treatment. At the same time, recent developments in high-resolution mass spectrometry have provided the technology for searching the drug targets across the whole cell proteomes. This review provides a concise description of the main objectives and problems of mass spectrometry-based chemical proteomics, the methods and approaches to their solution, and examples of implementation of these methods in biomedical research.
Topics: Drug Delivery Systems; Drug Discovery; Mass Spectrometry; Proteome; Proteomics
PubMed: 36180990
DOI: 10.1134/S0006297922090103 -
Chembiochem : a European Journal of... May 2022The mitochondrion is the core site of cell signaling, energy metabolism and biosynthesis. Here, taking advantage of activity-based probes, we synthesized two...
The mitochondrion is the core site of cell signaling, energy metabolism and biosynthesis. Here, taking advantage of activity-based probes, we synthesized two photocontrollable probes (YGH-1 and YGH-2), composed of a mitochondrial localization moiety "triphenylphosphonium", a photo-triggered group to achieve spatially and temporally controlled protein capture, and an alkyne group to enrich the labeled protein. Proteomic validation was further carried out to facilitate identification of the mitochondrial proteome in HeLa cells. The results show that half of the identified protein hits (ā¼300) labeled by YGH-1 and YGH-2 belong to mitochondria, and are mostly localized in the mitochondrial matrix and inner mitochondrial membrane. Our results provide a new tool for spatial and temporal analysis of subcellular proteomes.
Topics: HeLa Cells; Humans; Mitochondria; Mitochondrial Proteins; Proteome; Proteomics
PubMed: 35344259
DOI: 10.1002/cbic.202200066 -
Current Opinion in Chemical Biology Feb 2020Small molecule metabolites play important roles in regulating protein functions, which are acted through either covalent non-enzymatic post-translational... (Review)
Review
Small molecule metabolites play important roles in regulating protein functions, which are acted through either covalent non-enzymatic post-translational modificationsĀ or non-covalent binding interactions. Chemical proteomic strategies can help delineate global landscapes of cellular protein-metabolite interactions and provide molecular insights about their mechanisms of action. In this review, we summarized the recent progress in developments and applications of chemoproteomic strategies to profile protein-metabolite interactions.
Topics: Animals; Humans; Metabolome; Metabolomics; Proteins; Proteome; Proteomics
PubMed: 31812894
DOI: 10.1016/j.cbpa.2019.11.003 -
Expert Review of Proteomics Mar 2021Proteomics, i.e. the study of the set of proteins produced in a cell, tissue, organism, or biological entity, has made possible analyses and contextual comparisons of... (Review)
Review
INTRODUCTION
Proteomics, i.e. the study of the set of proteins produced in a cell, tissue, organism, or biological entity, has made possible analyses and contextual comparisons of proteomes/proteins and biological functions among the most disparate entities, from viruses to the human being. In this way, proteomic scrutiny of tumor-associated proteins, autoantigens, and pathogen antigens offers the tools for fighting cancer, autoimmunity, and infections.
AREAS COVERED
Comparative proteomics and immunoproteomics, the new scientific disciplines generated by proteomics, are the main themes of the present review that describes how comparative analyses of pathogen and human proteomes led to re-modulate the molecular mimicry concept of the pre-proteomic era. I.e. before proteomics, molecular mimicry - the sharing of peptide sequences between two biological entities - was considered as intrinsically endowed with immunologic properties and was related to cross-reactivity. Proteomics allowed to redefine such an assumption using physicochemical parameters according to which frequency and hydrophobicity preferentially confer an immunologic potential to shared peptide sequences.
EXPERT OPINION
Proteomics is outlining peptide platforms to be used for the diagnostics and management of human diseases. A Molecular Medicine targeted to obtain healing without paying the price for adverse events is on the horizon. The next step is to take up the challenge and operate the paradigm shift that the current proteomic era requires.
Topics: Autoantigens; Autoimmunity; Cross Reactions; Humans; Proteome; Proteomics
PubMed: 33825594
DOI: 10.1080/14789450.2021.1914595 -
Plant Physiology May 2021Protein cysteine residues are susceptible to oxidative modifications that can affect protein functions. Proteomic techniques that comprehensively profile the cysteine... (Review)
Review
Protein cysteine residues are susceptible to oxidative modifications that can affect protein functions. Proteomic techniques that comprehensively profile the cysteine redoxome, the repertoire of oxidized cysteine residues, are pivotal towards a better understanding of the protein redox signaling. Recent technical advances in chemical tools and redox proteomic strategies have greatly improved selectivity, in vivo applicability, and quantification of the cysteine redoxome. Despite this substantial progress, still many challenges remain. Here, we provide an update on the recent advances in proteomic strategies for cysteine redoxome profiling, compare the advantages and disadvantages of current methods and discuss the outstanding challenges and future perspectives for plant redoxome research.
Topics: Cysteine; Metabolome; Oxidation-Reduction; Plant Proteins; Plants; Proteome; Proteomics
PubMed: 33793888
DOI: 10.1093/plphys/kiaa074