Pub Date : 2022-03-01DOI: 10.1080/14789450.2022.2134780
Yangyang Bian, Chunli Gao, Bernhard Kuster
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.
{"title":"On the potential of micro-flow LC-MS/MS in proteomics.","authors":"Yangyang Bian, Chunli Gao, Bernhard Kuster","doi":"10.1080/14789450.2022.2134780","DOIUrl":"https://doi.org/10.1080/14789450.2022.2134780","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Areas covered: </strong>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.</p><p><strong>Expert opinion: </strong>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.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10478175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniases, associated with skin inflammation and ulceration. Understanding the interaction of different phagocytic cells in the recognition and uptake of different Leishmania species is critical for controlling the infection. Phagocytic cells have a pivotal role as professional antigen-presenting cells that bridge the innate and adaptive immunity and shape the outcome of the disease.
Areas covered: Here we reviewed new technologies with high-throughput data collection capabilities along with systems biology approaches which are recently being used to decode the paradox of CL immunology.
Expert opinion: We emphasized on the crosstalk between DC and T-cells while focusing on the immune checkpoints interactions between the human immune system and the Leishmania species. Further, we discussed omics technologies including bulk RNA sequencing, reverse transcriptase-multiplex ligation dependent probe amplification (RT-MLPA), and proximity extension assay (PEA) in studies on human blood or tissue-driven samples from CL patients in which we have so far been involved.
{"title":"Cutaneous leishmaniasis: multiomics approaches to unravel the role of immune cells checkpoints.","authors":"Yasaman Taslimi, Nasrin Masoudzadeh, Fariborz Bahrami, Sima Rafati","doi":"10.1080/14789450.2022.2131545","DOIUrl":"https://doi.org/10.1080/14789450.2022.2131545","url":null,"abstract":"<p><strong>Introduction: </strong>Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniases, associated with skin inflammation and ulceration. Understanding the interaction of different phagocytic cells in the recognition and uptake of different <i>Leishmania</i> species is critical for controlling the infection. Phagocytic cells have a pivotal role as professional antigen-presenting cells that bridge the innate and adaptive immunity and shape the outcome of the disease.</p><p><strong>Areas covered: </strong>Here we reviewed new technologies with high-throughput data collection capabilities along with systems biology approaches which are recently being used to decode the paradox of CL immunology.</p><p><strong>Expert opinion: </strong>We emphasized on the crosstalk between DC and T-cells while focusing on the immune checkpoints interactions between the human immune system and the <i>Leishmania</i> species. Further, we discussed omics technologies including bulk RNA sequencing, reverse transcriptase-multiplex ligation dependent probe amplification (RT-MLPA), and proximity extension assay (PEA) in studies on human blood or tissue-driven samples from CL patients in which we have so far been involved.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10836496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-01DOI: 10.1080/14789450.2022.2085563
Shivani Krishna Kapuganti, Aparna Bhardwaj, Prateek Kumar, Taniya Bhardwaj, Namyashree Nayak, Vladimir N Uversky, Rajanish Giri
Introduction: The life cycle of a virus involves interacting with the host cell, entry, hijacking host machinery for viral replication, evading the host's immune system, and releasing mature virions. However, viruses, being small in size, can only harbor a genome large enough to code for the minimal number of proteins required for the replication and maturation of the virions. As a result, many viral proteins are multifunctional machines that do not directly obey the classic structure-function paradigm. Often, such multifunctionality is rooted in intrinsic disorder that allows viral proteins to interact with various cellular factors and remain functional in the hostile environment of different cellular compartments.
Areas covered: This report covers the classification of flaviviruses, their proteome organization, and the prevalence of intrinsic disorder in the proteomes of different flaviviruses. Further, we have summarized the speculations made about the apparent roles of intrinsic disorder in the observed multifunctionality of flaviviral proteins.
Expert opinion: Small sizes of viral genomes impose multifunctionality on their proteins, which is dependent on the excessive usage of intrinsic disorder. In fact, intrinsic disorder serves as a universal functional tool, weapon, and armor of viruses and clearly plays an important role in their functionality and evolution.
{"title":"Role of structural disorder in the multi-functionality of flavivirus proteins.","authors":"Shivani Krishna Kapuganti, Aparna Bhardwaj, Prateek Kumar, Taniya Bhardwaj, Namyashree Nayak, Vladimir N Uversky, Rajanish Giri","doi":"10.1080/14789450.2022.2085563","DOIUrl":"https://doi.org/10.1080/14789450.2022.2085563","url":null,"abstract":"<p><strong>Introduction: </strong>The life cycle of a virus involves interacting with the host cell, entry, hijacking host machinery for viral replication, evading the host's immune system, and releasing mature virions. However, viruses, being small in size, can only harbor a genome large enough to code for the minimal number of proteins required for the replication and maturation of the virions. As a result, many viral proteins are multifunctional machines that do not directly obey the classic structure-function paradigm. Often, such multifunctionality is rooted in intrinsic disorder that allows viral proteins to interact with various cellular factors and remain functional in the hostile environment of different cellular compartments.</p><p><strong>Areas covered: </strong>This report covers the classification of flaviviruses, their proteome organization, and the prevalence of intrinsic disorder in the proteomes of different flaviviruses. Further, we have summarized the speculations made about the apparent roles of intrinsic disorder in the observed multifunctionality of flaviviral proteins.</p><p><strong>Expert opinion: </strong>Small sizes of viral genomes impose multifunctionality on their proteins, which is dependent on the excessive usage of intrinsic disorder. In fact, intrinsic disorder serves as a universal functional tool, weapon, and armor of viruses and clearly plays an important role in their functionality and evolution.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10485449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-01DOI: 10.1080/14789450.2022.2067530
H. Reikvam, A. Hemsing, M. Hernandez-Valladares, E. Birkeland
Acute myelogenous leukemia (AML) is a highly malignant disease of the blood and bone marrow [1]. A block in differentiation in normal hematopoiesis leads to accumulation of immature cells that compromise normal bone marrow function, resulting in severe bone marrow failure [1]. The disease has a highly malignant and aggressive course, and without treatment, the disease will usually be fatal within weeks to months. In contrast to breakthroughs in treating other cancers, the progress of therapy in AML has been slow overall, although new drugs have recently entered the field [2]. Furthermore, AML represents a various disease spectrum, reflected by a myriad of cytogenetic abnormalities and genetic mutations. Although well recognized and highly predictive, they do not fully capture the degree of heterogeneities manifested clinically. Disease heterogeneity resulting from variability in leukemic cell maturation state, a large diversity of genetic aberrations among patients, and the existence of multiple disease clones within a single patient have been extensively characterized. However, despite the extensive adoption of genomic approaches in cancer research, it is widely recognized that genomics alone is insufficient to provide an accurate picture of all cellular changes and dynamic states. In contrast, mass spectrometry (MS)-based proteomics has the potential to untangle the intracellular specter of intracellular proteins and hence complement limitations of genomic approaches, advancing the discovery of a potential therapeutic and druggable protein for improving personalized treatments in AML.
{"title":"Proteomic approaches for untangling pharmacological targets in acute myelogenous leukemia","authors":"H. Reikvam, A. Hemsing, M. Hernandez-Valladares, E. Birkeland","doi":"10.1080/14789450.2022.2067530","DOIUrl":"https://doi.org/10.1080/14789450.2022.2067530","url":null,"abstract":"Acute myelogenous leukemia (AML) is a highly malignant disease of the blood and bone marrow [1]. A block in differentiation in normal hematopoiesis leads to accumulation of immature cells that compromise normal bone marrow function, resulting in severe bone marrow failure [1]. The disease has a highly malignant and aggressive course, and without treatment, the disease will usually be fatal within weeks to months. In contrast to breakthroughs in treating other cancers, the progress of therapy in AML has been slow overall, although new drugs have recently entered the field [2]. Furthermore, AML represents a various disease spectrum, reflected by a myriad of cytogenetic abnormalities and genetic mutations. Although well recognized and highly predictive, they do not fully capture the degree of heterogeneities manifested clinically. Disease heterogeneity resulting from variability in leukemic cell maturation state, a large diversity of genetic aberrations among patients, and the existence of multiple disease clones within a single patient have been extensively characterized. However, despite the extensive adoption of genomic approaches in cancer research, it is widely recognized that genomics alone is insufficient to provide an accurate picture of all cellular changes and dynamic states. In contrast, mass spectrometry (MS)-based proteomics has the potential to untangle the intracellular specter of intracellular proteins and hence complement limitations of genomic approaches, advancing the discovery of a potential therapeutic and druggable protein for improving personalized treatments in AML.","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75889233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-01DOI: 10.1080/14789450.2022.2052849
J. Morales-Sanfrutos, J. Muñoz
ABSTRACT Introduction The field of extracellular vesicles (EVs) is rapidly advancing. This progress is fueled by the applications of these agents as biomarkers and also as an attractive source to encapsulate therapeutics. Areas covered Different types of EVs, including exosomes, and other nanoparticles have been identified with key regulatory functions in cell–cell communication. However, the techniques used for their purification possess inherent limitations, resulting in heterogeneous preparations contaminated by other EVs subtypes and nano-size structures. It is therefore urgent to deconvolute the molecular constituents present in each type of EVs in order to accurately ascribe their specific functions. In this context, proteomics can profile, not only the lumen proteins and surface markers, but also their post-translational modifications, which will inform on the mechanisms of cargo selection and sorting. Expert opinion Mass spectrometry-based proteomics is now a mature technique and has started to deliver new insights in the EV field. Here, we review recent developments in sample preparation, mass spectrometry (MS) and computational analysis and discuss how these advances, in conjunction with improved purification protocols, could impact thecharacterization of the complex landscape of EVs and other secreted nanoparticles.
{"title":"Unraveling the complexity of the extracellular vesicle landscape with advanced proteomics","authors":"J. Morales-Sanfrutos, J. Muñoz","doi":"10.1080/14789450.2022.2052849","DOIUrl":"https://doi.org/10.1080/14789450.2022.2052849","url":null,"abstract":"ABSTRACT Introduction The field of extracellular vesicles (EVs) is rapidly advancing. This progress is fueled by the applications of these agents as biomarkers and also as an attractive source to encapsulate therapeutics. Areas covered Different types of EVs, including exosomes, and other nanoparticles have been identified with key regulatory functions in cell–cell communication. However, the techniques used for their purification possess inherent limitations, resulting in heterogeneous preparations contaminated by other EVs subtypes and nano-size structures. It is therefore urgent to deconvolute the molecular constituents present in each type of EVs in order to accurately ascribe their specific functions. In this context, proteomics can profile, not only the lumen proteins and surface markers, but also their post-translational modifications, which will inform on the mechanisms of cargo selection and sorting. Expert opinion Mass spectrometry-based proteomics is now a mature technique and has started to deliver new insights in the EV field. Here, we review recent developments in sample preparation, mass spectrometry (MS) and computational analysis and discuss how these advances, in conjunction with improved purification protocols, could impact thecharacterization of the complex landscape of EVs and other secreted nanoparticles.","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72831063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-01DOI: 10.1080/14789450.2022.2052850
H. Hirano, Jun Shirakawa
ABSTRACT Introduction Phosphate-binding tag (Phos-tag) sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) is an important development capable of analyzing the phosphorylation state of proteins. Conventionally, proteins were separated via SDS-PAGE and Phos-tag SDS-PAGE that use different gels to identify phosphorylated proteins. However, it was often difficult to compare the electrophoretic mobility of the proteins in the different gels used. The recently developed Phos-tag diagonal electrophoresis has been able to solve this problem. It can indicate the SDS-PAGE and Phos-tag SDS-PAGE patterns on a single gel; therefore, phosphorylated proteins can be distinguished easily from non-phosphorylated proteins. Areas covered This review assesses the importance of Phos-tag electrophoresis, which enables the analysis of protein phosphorylation states, in the field of proteomics. Additionally, this review describes the significance and actual experimental technique of Phos-tag diagonal electrophoresis, which was recently developed to overcome the drawbacks of Phos-tag SDS-PAGE. Expert opinion Although shotgun analysis of proteins allows detecting many phosphorylation sites, it is challenging to clarify the differences in the phosphorylation states of protein molecules using this technique. Therefore, Phos-tag SDS-PAGE is frequently used to determine the phosphorylation state of proteins. This technique has become more powerful with the recent development of Phos-tag diagonal electrophoresis. Abbreviations: BIS, N,N’-methylenebis(acrylamide); CBB, Coomassie brilliant blue R250; ESI, electrospray ionization; hnRNP, heterogeneous ribonucleoprotein K; LTQ–Orbitrap, Linear trap quadrupole–Orbitrap; LC, liquid chromatography; MS, mass spectrometry; MALDI, matrix-assisted laser desorption ionization; Phos-tag, phosphate-binding tag [1,3-bis [bis (pyridine-2-ylmethyl) amino] propane-2-olate]; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; TOF, time of flight; 2D-DIGE, fluorescence-labeled two-dimensional difference gel electrophoresis; 2-DE, two-dimensional gel electrophoresis
{"title":"Recent developments in Phos-tag electrophoresis for the analysis of phosphoproteins in proteomics","authors":"H. Hirano, Jun Shirakawa","doi":"10.1080/14789450.2022.2052850","DOIUrl":"https://doi.org/10.1080/14789450.2022.2052850","url":null,"abstract":"ABSTRACT Introduction Phosphate-binding tag (Phos-tag) sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) is an important development capable of analyzing the phosphorylation state of proteins. Conventionally, proteins were separated via SDS-PAGE and Phos-tag SDS-PAGE that use different gels to identify phosphorylated proteins. However, it was often difficult to compare the electrophoretic mobility of the proteins in the different gels used. The recently developed Phos-tag diagonal electrophoresis has been able to solve this problem. It can indicate the SDS-PAGE and Phos-tag SDS-PAGE patterns on a single gel; therefore, phosphorylated proteins can be distinguished easily from non-phosphorylated proteins. Areas covered This review assesses the importance of Phos-tag electrophoresis, which enables the analysis of protein phosphorylation states, in the field of proteomics. Additionally, this review describes the significance and actual experimental technique of Phos-tag diagonal electrophoresis, which was recently developed to overcome the drawbacks of Phos-tag SDS-PAGE. Expert opinion Although shotgun analysis of proteins allows detecting many phosphorylation sites, it is challenging to clarify the differences in the phosphorylation states of protein molecules using this technique. Therefore, Phos-tag SDS-PAGE is frequently used to determine the phosphorylation state of proteins. This technique has become more powerful with the recent development of Phos-tag diagonal electrophoresis. Abbreviations: BIS, N,N’-methylenebis(acrylamide); CBB, Coomassie brilliant blue R250; ESI, electrospray ionization; hnRNP, heterogeneous ribonucleoprotein K; LTQ–Orbitrap, Linear trap quadrupole–Orbitrap; LC, liquid chromatography; MS, mass spectrometry; MALDI, matrix-assisted laser desorption ionization; Phos-tag, phosphate-binding tag [1,3-bis [bis (pyridine-2-ylmethyl) amino] propane-2-olate]; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; TOF, time of flight; 2D-DIGE, fluorescence-labeled two-dimensional difference gel electrophoresis; 2-DE, two-dimensional gel electrophoresis","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83862765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-01DOI: 10.1080/14789450.2022.2070477
L. Dayon, O. Cominetti, M. Affolter
ABSTRACT Introduction Biological fluids are routine samples for diagnostic testing and monitoring. Blood samples are typically measured because of their moderate invasive collection and high information content on health and disease. Several body fluids, such as cerebrospinal fluid (CSF), are also studied and suited to specific pathologies. Over the last two decades, proteomics has quested to identify protein biomarkers but with limited success. Recent technologies and refined pipelines have accelerated the profiling of human biological fluids. Areas covered We review proteomic technologies for the identification of biomarkers. These are based on antibodies/aptamers arrays or mass spectrometry (MS), but new ones are emerging. Advances in scalability and throughput have allowed to better design studies and cope with the limited sample size that has until now prevailed due to technological constraints. With these enablers, plasma/serum, CSF, saliva, tears, urine, and milk proteomes have been further profiled; we provide a non-exhaustive picture of some recent highlights (mainly covering literature from the last 5 years in the Scopus database) using MS-based proteomics. Expert opinion While proteomics has been in the shadow of genomics for years, proteomic tools and methodologies have reached certain maturity. They are now better suited to discover innovative and robust biofluid biomarkers.
{"title":"Proteomics of human biological fluids for biomarker discoveries: technical advances and recent applications","authors":"L. Dayon, O. Cominetti, M. Affolter","doi":"10.1080/14789450.2022.2070477","DOIUrl":"https://doi.org/10.1080/14789450.2022.2070477","url":null,"abstract":"ABSTRACT Introduction Biological fluids are routine samples for diagnostic testing and monitoring. Blood samples are typically measured because of their moderate invasive collection and high information content on health and disease. Several body fluids, such as cerebrospinal fluid (CSF), are also studied and suited to specific pathologies. Over the last two decades, proteomics has quested to identify protein biomarkers but with limited success. Recent technologies and refined pipelines have accelerated the profiling of human biological fluids. Areas covered We review proteomic technologies for the identification of biomarkers. These are based on antibodies/aptamers arrays or mass spectrometry (MS), but new ones are emerging. Advances in scalability and throughput have allowed to better design studies and cope with the limited sample size that has until now prevailed due to technological constraints. With these enablers, plasma/serum, CSF, saliva, tears, urine, and milk proteomes have been further profiled; we provide a non-exhaustive picture of some recent highlights (mainly covering literature from the last 5 years in the Scopus database) using MS-based proteomics. Expert opinion While proteomics has been in the shadow of genomics for years, proteomic tools and methodologies have reached certain maturity. They are now better suited to discover innovative and robust biofluid biomarkers.","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88608614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-01DOI: 10.1080/14789450.2022.2070065
Ann M Cathcart, Hannah Smith, Marilyne Labrie, Gordon B Mills
Introduction: Drug resistance is the main barrier to achieving cancer cures with medical therapy. Cancer drug resistance occurs, in part, due to adaptation of the tumor and microenvironment to therapeutic stress at a proteomic level. Reverse-phase protein arrays (RPPA) are well suited to proteomic analysis of drug resistance due to high sample throughput, sensitive detection of phosphoproteins, and validation for a large number of critical cellular pathways.
Areas covered: This review summarizes contributions of RPPA to understanding and combating drug resistance. In particular, contributions of RPPA to understanding resistance to PARP inhibitors, BRAF inhibitors, immune checkpoint inhibitors, and breast cancer investigational therapies are discussed. Articles reviewed were identified by MEDLINE, Scopus, and Cochrane search for keywords 'proteomics,' 'reverse-phase protein array,' 'drug resistance,' 'PARP inhibitor,' 'BRAF inhibitor,' 'immune checkpoint inhibitor,' and 'I-SPY' spanning October 1, 1960 - October 1, 2021.
Expert opinion: Precision oncology has thus far failed to convert the armament of targeted therapies into durable responses for most patients, highlighting that genetic sequencing alone is insufficient to guide therapy selection and overcome drug resistance. Combined genomic and proteomic analyses paired with creative drug combinations and dosing strategies hold promise for maturing precision oncology into an era of improved patient outcomes.
{"title":"Characterization of anticancer drug resistance by reverse-phase protein array: new targets and strategies.","authors":"Ann M Cathcart, Hannah Smith, Marilyne Labrie, Gordon B Mills","doi":"10.1080/14789450.2022.2070065","DOIUrl":"https://doi.org/10.1080/14789450.2022.2070065","url":null,"abstract":"<p><strong>Introduction: </strong>Drug resistance is the main barrier to achieving cancer cures with medical therapy. Cancer drug resistance occurs, in part, due to adaptation of the tumor and microenvironment to therapeutic stress at a proteomic level. Reverse-phase protein arrays (RPPA) are well suited to proteomic analysis of drug resistance due to high sample throughput, sensitive detection of phosphoproteins, and validation for a large number of critical cellular pathways.</p><p><strong>Areas covered: </strong>This review summarizes contributions of RPPA to understanding and combating drug resistance. In particular, contributions of RPPA to understanding resistance to PARP inhibitors, BRAF inhibitors, immune checkpoint inhibitors, and breast cancer investigational therapies are discussed. Articles reviewed were identified by MEDLINE, Scopus, and Cochrane search for keywords 'proteomics,' 'reverse-phase protein array,' 'drug resistance,' 'PARP inhibitor,' 'BRAF inhibitor,' 'immune checkpoint inhibitor,' and 'I-SPY' spanning October 1, 1960 - October 1, 2021.</p><p><strong>Expert opinion: </strong>Precision oncology has thus far failed to convert the armament of targeted therapies into durable responses for most patients, highlighting that genetic sequencing alone is insufficient to guide therapy selection and overcome drug resistance. Combined genomic and proteomic analyses paired with creative drug combinations and dosing strategies hold promise for maturing precision oncology into an era of improved patient outcomes.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9215307/pdf/nihms-1800725.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9346120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-01DOI: 10.1080/14789450.2022.2064278
M. Nielsen, N. Ternette, C. Barra
ABSTRACT Introduction The comprehensive collection of peptides presented by major histocompatibility complex (MHC) molecules on the cell surface is collectively known as the immunopeptidome. The analysis and interpretation of such data sets holds great promise for furthering our understanding of basic immunology and adaptive immune activation and regulation, and for direct rational discovery of T cell antigens and the design of T-cell-based therapeutics and vaccines. These applications are, however, challenged by the complex nature of immunopeptidome data. Areas covered Here, we describe the benefits and shortcomings of applying liquid chromatography-tandem mass spectrometry (MS) to obtain large-scale immunopeptidome data sets and illustrate how the accurate analysis and optimal interpretation of such data is reliant on the availability of refined and highly optimized machine learning approaches. Expert opinion Further, we demonstrate how the accuracy of immunoinformatics prediction methods within the field of MHC antigen presentation has benefited greatly from the availability of MS-immunopeptidomics data, and exemplify how optimal antigen discovery is best performed in a synergistic combination of MS experiments and such in silico models trained on large-scale immunopeptidomics data.
{"title":"The interdependence of machine learning and LC-MS approaches for an unbiased understanding of the cellular immunopeptidome","authors":"M. Nielsen, N. Ternette, C. Barra","doi":"10.1080/14789450.2022.2064278","DOIUrl":"https://doi.org/10.1080/14789450.2022.2064278","url":null,"abstract":"ABSTRACT Introduction The comprehensive collection of peptides presented by major histocompatibility complex (MHC) molecules on the cell surface is collectively known as the immunopeptidome. The analysis and interpretation of such data sets holds great promise for furthering our understanding of basic immunology and adaptive immune activation and regulation, and for direct rational discovery of T cell antigens and the design of T-cell-based therapeutics and vaccines. These applications are, however, challenged by the complex nature of immunopeptidome data. Areas covered Here, we describe the benefits and shortcomings of applying liquid chromatography-tandem mass spectrometry (MS) to obtain large-scale immunopeptidome data sets and illustrate how the accurate analysis and optimal interpretation of such data is reliant on the availability of refined and highly optimized machine learning approaches. Expert opinion Further, we demonstrate how the accuracy of immunoinformatics prediction methods within the field of MHC antigen presentation has benefited greatly from the availability of MS-immunopeptidomics data, and exemplify how optimal antigen discovery is best performed in a synergistic combination of MS experiments and such in silico models trained on large-scale immunopeptidomics data.","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74431539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2021-12-13DOI: 10.1080/14789450.2021.2012454
Sedireng M Ndolo, Matshediso Zachariah, Lebotse Molefi, Nthabiseng Phaladze, Kwenga F Sichilongo
Introduction: Metabolomics for identifying schistosomiasis biomarkers in noninvasive samples at various infection stages is being actively explored. The literature on the traditional detection of schistosomiasis in human specimens is well documented. However, state-of-the-art technologies based on mass spectrometry have simplified the use of biomarkers for diagnostics. This review examines methods currently in use for the metabolomics of small molecules using separation science and mass spectrometry.
Area covered: This article highlights the evolution of traditional diagnostic methods for schistosomiasis based on inter alia microscopy, immunology, and polymerase chain reaction. An exhaustive literature search of metabolite mining, focusing on separation science and mass spectrometry, is presented. A comparative analysis of mass spectrometry methods was undertaken, including a projection for the future.
Expert commentary: Mass spectrometry metabolomics for schistosomiasis will lead to biomarker discovery for noninvasive human samples. These biomarkers, together with those from other neglected tropical diseases, such as malaria and sleeping sickness, could be incorporated as arrays on a single biosensor chip and inserted into smartphones, in order to improve surveillance, monitoring, and management.
{"title":"Mass spectrometry based metabolomics for small molecule metabolites mining and confirmation as potential biomarkers for schistosomiasis - case of the Okavango Delta communities in Botswana.","authors":"Sedireng M Ndolo, Matshediso Zachariah, Lebotse Molefi, Nthabiseng Phaladze, Kwenga F Sichilongo","doi":"10.1080/14789450.2021.2012454","DOIUrl":"https://doi.org/10.1080/14789450.2021.2012454","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolomics for identifying schistosomiasis biomarkers in noninvasive samples at various infection stages is being actively explored. The literature on the traditional detection of schistosomiasis in human specimens is well documented. However, state-of-the-art technologies based on mass spectrometry have simplified the use of biomarkers for diagnostics. This review examines methods currently in use for the metabolomics of small molecules using separation science and mass spectrometry.</p><p><strong>Area covered: </strong>This article highlights the evolution of traditional diagnostic methods for schistosomiasis based on inter alia microscopy, immunology, and polymerase chain reaction. An exhaustive literature search of metabolite mining, focusing on separation science and mass spectrometry, is presented. A comparative analysis of mass spectrometry methods was undertaken, including a projection for the future.</p><p><strong>Expert commentary: </strong>Mass spectrometry metabolomics for schistosomiasis will lead to biomarker discovery for noninvasive human samples. These biomarkers, together with those from other neglected tropical diseases, such as malaria and sleeping sickness, could be incorporated as arrays on a single biosensor chip and inserted into smartphones, in order to improve surveillance, monitoring, and management.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39945439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}