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Journal of Chemical Information and... Dec 2022Spatial proteomics is an interdisciplinary field that investigates the localization and dynamics of proteins, and it has gained extensive attention in recent years,... (Review)
Review
Spatial proteomics is an interdisciplinary field that investigates the localization and dynamics of proteins, and it has gained extensive attention in recent years, especially the subcellular proteomics. Numerous evidence indicate that the subcellular localization of proteins is associated with various cellular processes and disease progression. Mass spectrometry (MS)-based and imaging-based experimental approaches have been developed to acquire large-scale spatial proteomic data. To allow the reliable analysis of increasingly complex spatial proteomics data, machine learning (ML) methods have been widely used in both MS-based and imaging-based spatial proteomic data analysis pipelines. Here, we comprehensively survey the applications of ML in spatial proteomics from following aspects: (1) data resources for spatial proteome are comprehensively introduced; (2) the roles of different ML algorithms in data analysis pipelines are elaborated; (3) successful applications of spatial proteomics and several analytical tools integrating ML methods are presented; (4) challenges existing in modern ML-based spatial proteomics studies are discussed. This review provides guidelines for researchers seeking to apply ML methods to analyze spatial proteomic data and can facilitate insightful understanding of cell biology as well as the future research in medical and drug discovery communities.
Topics: Proteomics; Proteome; Mass Spectrometry; Machine Learning; Algorithms
PubMed: 36378082
DOI: 10.1021/acs.jcim.2c01161 -
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 -
Reproduction (Cambridge, England) Nov 2015Spermatogenesis is a complex and tightly regulated process leading to the continuous production of male gametes, the spermatozoa. This developmental process requires the... (Review)
Review
Spermatogenesis is a complex and tightly regulated process leading to the continuous production of male gametes, the spermatozoa. This developmental process requires the sequential and coordinated expression of thousands of genes, including many that are testis-specific. The molecular networks underlying normal and pathological spermatogenesis have been widely investigated in recent decades, and many high-throughput expression studies have studied genes and proteins involved in male fertility. In this review, we focus on studies that have attempted to correlate transcription and translation during spermatogenesis by comparing the testicular transcriptome and proteome. We also discuss the recent development and use of new transcriptomic approaches that provide a better proxy for the proteome, from both qualitative and quantitative perspectives. Finally, we provide illustrations of how testis-derived transcriptomic and proteomic data can be integrated to address new questions and how the 'proteomics informed by transcriptomics' technique, by combining RNA-seq and MS-based proteomics, can contribute significantly to the discovery of new protein-coding genes or new protein isoforms expressed during spermatogenesis.
Topics: Animals; Gene Expression Regulation; Humans; Male; Proteome; Proteomics; Spermatogenesis; Transcriptome
PubMed: 26416010
DOI: 10.1530/REP-15-0073 -
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 -
Annual Review of Pathology Jan 2017Amyloidoses are a spectrum of disorders caused by abnormal folding and extracellular deposition of proteins. The deposits lead to tissue damage and organ dysfunction,... (Review)
Review
Amyloidoses are a spectrum of disorders caused by abnormal folding and extracellular deposition of proteins. The deposits lead to tissue damage and organ dysfunction, particularly in the heart, kidneys, and nerves. There are at least 30 different proteins that can cause amyloidosis. The clinical management depends entirely on the type of protein deposited, and thus on the underlying pathogenesis, and often requires high-risk therapeutic intervention. Application of mass spectrometry-based proteomic technologies for analysis of amyloid plaques has transformed the way amyloidosis is diagnosed and classified. Proteomic assays have been extensively used for clinical management of patients with amyloidosis, providing unprecedented diagnostic and biological information. They have shed light on the pathogenesis of different amyloid types and have led to identification of numerous new amyloid types, including ALECT2 amyloidosis, which is now recognized as one of the most common causes of systemic amyloidosis in North America.
Topics: Amyloidosis; Animals; Humans; Proteome; Proteomics
PubMed: 27959636
DOI: 10.1146/annurev-pathol-052016-100200 -
Proteomics Dec 2014A single eukaryotic gene can give rise to a variety of protein forms (proteoforms) as a result of genetic variation and multilevel regulation of gene expression. In... (Review)
Review
A single eukaryotic gene can give rise to a variety of protein forms (proteoforms) as a result of genetic variation and multilevel regulation of gene expression. In addition to alternative splicing, an increasing line of evidence shows that alternative translation contributes to the overall complexity of proteomes. Identifying the repertoire of proteins and micropeptides expressed by alternative selection of (near-)cognate translation initiation sites and different reading frames however remains challenging with contemporary proteomics. MS-enabled identification of proteoforms is expected to benefit from transcriptome and translatome data by the creation of customized and sample-specific protein sequence databases. Here, we focus on contemporary integrative omics approaches that complement proteomics with DNA- and/or RNA-oriented technologies to elucidate the mechanisms of translational control. Together, these technologies enable to map the translation (initiation) landscape and more comprehensively define the inventory of proteoforms raised upon alternative translation, thus assisting in the (re-)annotation of genomes.
Topics: Protein Biosynthesis; Proteome; Proteomics; Ribosomes; Systems Biology
PubMed: 25263132
DOI: 10.1002/pmic.201400165 -
Cell Systems Nov 2023Spatial proteomics combining microscopy-based cell phenotyping with ultrasensitive mass-spectrometry-based proteomics is an emerging and powerful concept to study cell...
Spatial proteomics combining microscopy-based cell phenotyping with ultrasensitive mass-spectrometry-based proteomics is an emerging and powerful concept to study cell function and heterogeneity in (patho)physiology. However, optimized workflows that preserve morphological information for phenotype discovery and maximize proteome coverage of few or even single cells from laser microdissected tissue are currently lacking. Here, we report a robust and scalable workflow for the proteomic analysis of ultra-low-input archival material. Benchmarking in murine liver resulted in up to 2,000 quantified proteins from single hepatocyte contours and nearly 5,000 proteins from 50-cell regions. Applied to human tonsil, we profiled 146 microregions including T and B lymphocyte niches and quantified cell-type-specific markers, cytokines, and transcription factors. These data also highlighted proteome dynamics within activated germinal centers, illuminating sites undergoing B cell proliferation and somatic hypermutation. This approach has broad implications in biomedicine, including early disease profiling and drug target and biomarker discovery. A record of this paper's transparent peer review process is included in the supplemental information.
Topics: Humans; Animals; Mice; Proteome; Proteomics; Mass Spectrometry
PubMed: 37909047
DOI: 10.1016/j.cels.2023.10.003 -
Current Protocols in Protein Science Feb 2019Stable isotope labeling by amino acids in cell culture (SILAC) has become very popular as a quantitative proteomic method since it was firstly introduced by Matthias... (Review)
Review
Stable isotope labeling by amino acids in cell culture (SILAC) has become very popular as a quantitative proteomic method since it was firstly introduced by Matthias Mann's group in 2002. It is a metabolic labeling strategy in which isotope-labeled amino acids are metabolically incorporated in vivo into proteins during translation. After natural (light) or heavy amino acid incorporation, differentially labeled samples are mixed immediately after cell lysis and before any further processing, which minimizes quantitative errors caused by handling different samples in parallel. In this unit, we describe protocols for basic duplex SILAC, triplex SILAC for use in nondividing cells such as neurons, and for measuring amounts of newly synthesized proteins. © 2018 by John Wiley & Sons, Inc.
Topics: Animals; Humans; Isotope Labeling; Nerve Tissue Proteins; Neurons; Proteome; Proteomics
PubMed: 30238645
DOI: 10.1002/cpps.74 -
Proteomics Jan 2017Given superior analytical features, MS proteomics is well suited for the basic investigation and clinical diagnosis of human disease. Modern MS enables detailed... (Review)
Review
Given superior analytical features, MS proteomics is well suited for the basic investigation and clinical diagnosis of human disease. Modern MS enables detailed functional characterization of the pathogenic biochemical processes, as achieved by accurate and comprehensive quantification of proteins and their regulatory chemical modifications. Here, we describe how high-accuracy MS in combination with high-resolution chromatographic separations can be leveraged to meet these analytical requirements in a mechanism-focused manner. We review the quantification methods capable of producing accurate measurements of protein abundance and posttranslational modification stoichiometries. We then discuss how experimental design and chromatographic resolution can be leveraged to achieve comprehensive functional characterization of biochemical processes in complex biological proteomes. Finally, we describe current approaches for quantitative analysis of a common functional protein modification: reversible phosphorylation. In all, current instrumentation and methods of high-resolution chromatography and MS proteomics are poised for immediate translation into improved diagnostic strategies for pediatric and adult diseases.
Topics: Humans; Mass Spectrometry; Protein Processing, Post-Translational; Proteome; Proteomics
PubMed: 27775219
DOI: 10.1002/pmic.201600079 -
Expert Review of Proteomics Mar 2018The clinical evaluation of neuromuscular symptoms often includes the assessment of altered blood proteins or changed enzyme activities. However, the blood concentration... (Review)
Review
The clinical evaluation of neuromuscular symptoms often includes the assessment of altered blood proteins or changed enzyme activities. However, the blood concentration of many muscle-derived serum markers is not specific for different neuromuscular disorders and also shows alterations in the course of these diseases. Thus, the establishment of more reliable biomarker signatures for improved muscle diagnostics is required. Areas covered: To address the lack of muscle disease-specific marker molecules, mass spectrometry-based proteomics was applied to the systematic identification and biochemical characterization of new serum biomarker candidates. This article outlines serum proteomics in relation to neuromuscular disorders and reviews the bioanalytical results from recent proteomic profiling studies of representative neuromuscular disorders, including motor neuron disease, muscular dystrophies and sarcopenia of old age. Pathophysiological changes in the skeletal muscle proteome are reflected by serum alterations in a variety of sarcomeric proteins, metabolic enzymes and signaling proteins. Expert commentary: Based on the proteomic identification of actively secreted or passively released skeletal muscle proteins following pathophysiological insults, new biomarker candidates can now be used to develop liquid biopsy procedures for superior diagnostic approaches, design novel prognostic tools and establish more reliable methods for the systematic evaluation of experimental therapies to treat neuromuscular disease.
Topics: Animals; Biomarkers; Humans; Neuromuscular Diseases; Proteome; Proteomics
PubMed: 29338453
DOI: 10.1080/14789450.2018.1429923