Sophia Weiner, Kaj Blennow, Henrik Zetterberg, Johan Gobom
{"title":"Next-generation proteomics technologies in Alzheimer's disease: from clinical research to routine diagnostics.","authors":"Sophia Weiner, Kaj Blennow, Henrik Zetterberg, Johan Gobom","doi":"10.1080/14789450.2023.2255752","DOIUrl":"10.1080/14789450.2023.2255752","url":null,"abstract":"<p><strong>Introduction: </strong>Clinical proteomics studies of Alzheimer's disease (AD) research aim to identify biomarkers useful for clinical research, diagnostics, and improve our understanding of the pathological processes involved in the disease. The rapidly increasing performance of proteomics technologies is likely to have great impact on AD research.</p><p><strong>Areas covered: </strong>We review recent proteomics approaches that have advanced the field of clinical AD research. Specifically, we discuss the application of targeted mass spectrometry (MS), labeling-based and label-free MS-based as well as affinity-based proteomics to AD biomarker development, underpinning their importance with the latest impactful clinical studies. We evaluate how proteomics technologies have been adapted to meet current challenges. Finally, we discuss the limitations and potential of proteomics techniques and whether their scope might extend beyond current research-based applications.</p><p><strong>Expert opinion: </strong>To date, proteomics technologies in the AD field have been largely limited to AD biomarker discovery. The recent development of the first successful disease-modifying treatments of AD will further increase the need for blood biomarkers for early, accurate diagnosis, and CSF biomarkers that reflect specific pathological processes. Proteomics has the potential to meet these requirements and to progress into clinical routine practice, provided that current limitations are overcome.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":" ","pages":"143-150"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10278636","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}
Philipp F Lange, Oliver Schilling, Pitter F Huesgen
{"title":"Positional proteomics: is the technology ready to study clinical cohorts?","authors":"Philipp F Lange, Oliver Schilling, Pitter F Huesgen","doi":"10.1080/14789450.2023.2272046","DOIUrl":"10.1080/14789450.2023.2272046","url":null,"abstract":"<p><strong>Introduction: </strong>Positional proteomics provides proteome-wide information on protein termini and their modifications, uniquely enabling unambiguous identification of site-specific, limited proteolysis. Such proteolytic cleavage irreversibly modifies protein sequences resulting in new proteoforms with distinct protease-generated neo-N and C-termini and altered localization and activity. Misregulated proteolysis is implicated in a wide variety of human diseases. Protein termini, therefore, constitute a huge, largely unexplored source of specific analytes that provides a deep view into the functional proteome and a treasure trove for biomarkers.</p><p><strong>Areas covered: </strong>We briefly review principal approaches to define protein termini and discuss recent advances in method development. We further highlight the potential of positional proteomics to identify and trace specific proteoforms, with a focus on proteolytic processes altered in disease. Lastly, we discuss current challenges and potential for applying positional proteomics in biomarker and pre-clinical research.</p><p><strong>Expert opinion: </strong>Recent developments in positional proteomics have provided significant advances in sensitivity and throughput. In-depth analysis of proteolytic processes in clinical cohorts thus appears feasible in the near future. We argue that this will provide insights into the functional state of the proteome and offer new opportunities to utilize proteolytic processes altered or targeted in disease as specific diagnostic, prognostic and companion biomarkers.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":" ","pages":"309-318"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693534","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}
{"title":"Proteomic profiling and network biology of colorectal cancer liver metastasis.","authors":"Rubén A Bartolomé, J Ignacio Casal","doi":"10.1080/14789450.2023.2275681","DOIUrl":"10.1080/14789450.2023.2275681","url":null,"abstract":"<p><strong>Introduction: </strong>Tissue-based proteomic studies of colorectal cancer (CRC) metastasis have delivered fragmented results, with very few therapeutic targets and prognostic biomarkers moving beyond the discovery phase. This situation is likely due to the difficulties in obtaining and analyzing large numbers of patient-derived metastatic samples, the own heterogeneity of CRC, and technical limitations in proteomics discovery. As an alternative, metastatic CRC cell lines provide a flexible framework to investigate the underlying mechanisms and network biology of metastasis for target discovery.</p><p><strong>Areas covered: </strong>In this perspective, we comment on different in-depth proteomic studies of metastatic versus non-metastatic CRC cell lines. Identified metastasis-related proteins are introduced and discussed according to the spatial location in different cellular fractions, with special emphasis on membrane/adhesion proteins, secreted proteins, and nuclear factors, including miRNAs associated with liver metastasis. Moreover, we analyze the biological significance and potential therapeutic applications of the identified liver metastasis-related proteins.</p><p><strong>Expert opinion: </strong>The combination of protein discovery and functional analysis is the only way to accelerate the progress to clinical translation of the proteomic-derived findings in a relatively fast pace. Patient-derived organoids represent a promising alternative to patient tissues and cell lines, but further optimizations are still required for achieving solid and reproducible results.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":" ","pages":"357-370"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693536","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}
Vasiliki Kanaka, Petros Drakakis, Dimitrios Loutradis, George Th Tsangaris
{"title":"Proteomics in the study of female fertility: an update.","authors":"Vasiliki Kanaka, Petros Drakakis, Dimitrios Loutradis, George Th Tsangaris","doi":"10.1080/14789450.2023.2275683","DOIUrl":"10.1080/14789450.2023.2275683","url":null,"abstract":"<p><strong>Introduction: </strong>Female fertility has been a field of interest for the scientific community throughout the years. The contribution of proteomics in the study of female fertility as well as female infertility and in vitro fertilization (IVF) has been significant. Proteomics is a recently developed field, extensively applied to the identification and quantification of proteins, which could be used as potential biomarkers in a diagnostic, prognostic, or predictive manner in a variety of medical conditions.</p><p><strong>Areas covered: </strong>The present review focuses on proteomic studies of the oocyte and endometrial environment as well as on conditions related to infertility, such as polycystic ovarian syndrome, endometriosis, obesity, and unexplained infertility. Moreover, this review presents studies that have been done in an effort to search for fertility biomarkers in individuals following the IVF procedure.</p><p><strong>Expert opinion: </strong>The comprehension of the molecular pathways behind female fertility and infertility could contribute to the diagnosis, prognosis, and prediction of infertility. Moreover, the identification of proteomic biomarkers for IVF cycles could predict the possible outcome of an IVF cycle, prevent an unsuccessful IVF, and monitor the IVF cycle in a personalized manner, leading to increased success rates. [Figure: see text].</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":" ","pages":"319-330"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693537","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}
{"title":"How to maximize power for differential expression analysis in discovery omics through experimental design.","authors":"Brenden Dufault, Richard D LeDuc, René P Zahedi","doi":"10.1080/14789450.2023.2287054","DOIUrl":"10.1080/14789450.2023.2287054","url":null,"abstract":"","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":" ","pages":"299-301"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138292300","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}
Katharina Zittlau, Payal Nashier, Claudia Cavarischia-Rega, Boris Macek, Philipp Spät, Nicolas Nalpas
{"title":"Recent progress in quantitative phosphoproteomics.","authors":"Katharina Zittlau, Payal Nashier, Claudia Cavarischia-Rega, Boris Macek, Philipp Spät, Nicolas Nalpas","doi":"10.1080/14789450.2023.2295872","DOIUrl":"10.1080/14789450.2023.2295872","url":null,"abstract":"<p><strong>Introduction: </strong>Protein phosphorylation is a critical post-translational modification involved in the regulation of numerous cellular processes from signal transduction to modulation of enzyme activities. Knowledge of dynamic changes of phosphorylation levels during biological processes, under various treatments or between healthy and disease models is fundamental for understanding the role of each phosphorylation event. Thereby, LC-MS/MS based technologies in combination with quantitative proteomics strategies evolved as a powerful strategy to investigate the function of individual protein phosphorylation events.</p><p><strong>Areas covered: </strong>State-of-the-art labeling techniques including stable isotope and isobaric labeling provide precise and accurate quantification of phosphorylation events. Here, we review the strengths and limitations of recent quantification methods and provide examples based on current studies, how quantitative phosphoproteomics can be further optimized for enhanced analytic depth, dynamic range, site localization, and data integrity. Specifically, reducing the input material demands is key to a broader implementation of quantitative phosphoproteomics, not least for clinical samples.</p><p><strong>Expert opinion: </strong>Despite quantitative phosphoproteomics is one of the most thriving fields in the proteomics world, many challenges still have to be overcome to facilitate even deeper and more comprehensive analyses as required in the current research, especially at single cell levels and in clinical diagnostics.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":" ","pages":"469-482"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812713","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}
Jong-Heon Kim, Ruqayya Afridi, Won-Ha Lee, Kyoungho Suk
{"title":"Analyzing the glial proteome in Alzheimer's disease.","authors":"Jong-Heon Kim, Ruqayya Afridi, Won-Ha Lee, Kyoungho Suk","doi":"10.1080/14789450.2023.2260955","DOIUrl":"10.1080/14789450.2023.2260955","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and changes in behavior. Accumulating evidence indicates that dysfunction of glial cells, including astrocytes, microglia, and oligodendrocytes, may contribute to the development and progression of AD. Large-scale analysis of glial proteins sheds light on their roles in cellular processes and diseases. In AD, glial proteomics has been utilized to understand glia-based pathophysiology and identify potential biomarkers and therapeutic targets.</p><p><strong>Area covered: </strong>In this review, we provide an updated overview of proteomic analysis of glia in the context of AD. Additionally, we discuss current challenges in the field, involving glial complexity and heterogeneity, and describe some cutting-edge proteomic technologies to address them.</p><p><strong>Expert opinion: </strong>Unbiased comprehensive analysis of glial proteomes aids our understanding of the molecular and cellular mechanisms of AD pathogenesis. These investigations highlight the crucial role of glial cells and provide novel insights into the mechanisms of AD pathology. A deeper understanding of the AD-related glial proteome could offer a repertoire of potential biomarkers and therapeutics. Further technical advancement of glial proteomics will enable us to identify proteins within individual cells and specific cell types, thus significantly enhancing our comprehension of AD pathogenesis.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":" ","pages":"197-209"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10363643","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}
Chiara Martinello, Emanuele Panza, Antonio Orlacchio
{"title":"Hereditary spastic paraplegias proteome: common pathways and pathogenetic mechanisms.","authors":"Chiara Martinello, Emanuele Panza, Antonio Orlacchio","doi":"10.1080/14789450.2023.2260952","DOIUrl":"10.1080/14789450.2023.2260952","url":null,"abstract":"<p><strong>Introduction: </strong>Hereditary spastic paraplegias (HSPs) are a group of inherited neurodegenerative disorders characterized by progressive spasticity and weakness of the lower limbs. These conditions are caused by lesions in the neuronal pyramidal tract and exhibit clinical and genetic variability. Ongoing research focuses on understanding the underlying mechanisms of HSP onset, which ultimately lead to neuronal degeneration. Key molecular mechanisms involved include axonal transport, cytoskeleton dynamics, myelination abnormalities, membrane trafficking, organelle morphogenesis, ER homeostasis, mitochondrial dysfunction, and autophagy deregulation.</p><p><strong>Areas covered: </strong>This review aims to provide an overview of the shared pathogenetic mechanisms in various forms of HSPs. By examining disease-causing gene products and their associated functional pathways, this understanding could lead to the discovery of new therapeutic targets and the development of treatments to modify the progression of the disease.</p><p><strong>Expert opinion: </strong>Investigating gene functionality is crucial for identifying shared pathogenetic pathways underlying different HSP subtypes. Categorizing protein function and identifying pathways aids in finding biomarkers, predicting early onset, and guiding treatment for a better quality of life. Targeting shared mechanisms enables efficient and cost-effective therapies. Prospects involve identifying new disease-causing genes, refining molecular processes, and implementing findings in diagnosis, key for advancing HSP understanding and developing effective treatments.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":" ","pages":"171-188"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41162342","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}
{"title":"Protein biomarkers for radiation injury and testing of medical countermeasure efficacy: promises, pitfalls, and future directions.","authors":"Vijay K Singh, Meera Srivastava, Thomas M Seed","doi":"10.1080/14789450.2023.2263652","DOIUrl":"10.1080/14789450.2023.2263652","url":null,"abstract":"<p><strong>Introduction: </strong>Radiological/nuclear accidents, hostile military activity, or terrorist strikes have the potential to expose a large number of civilians and military personnel to high doses of radiation resulting in the development of acute radiation syndrome and delayed effects of exposure. Thus, there is an urgent need for sensitive and specific assays to assess the levels of radiation exposure to individuals. Such radiation exposures are expected to alter primary cellular proteomic processes, resulting in multifaceted biological responses.</p><p><strong>Areas covered: </strong>This article covers the application of proteomics, a promising and fast developing technology based on quantitative and qualitative measurements of protein molecules for possible rapid measurement of radiation exposure levels. Recent advancements in high-resolution chromatography, mass spectrometry, high-throughput, and bioinformatics have resulted in comprehensive (relative quantitation) and precise (absolute quantitation) approaches for the discovery and accuracy of key protein biomarkers of radiation exposure. Such proteome biomarkers might prove useful for assessing radiation exposure levels as well as for extrapolating the pharmaceutical dose of countermeasures for humans based on efficacy data generated using animal models.</p><p><strong>Expert opinion: </strong>The field of proteomics promises to be a valuable asset in evaluating levels of radiation exposure and characterizing radiation injury biomarkers.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":" ","pages":"221-246"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138930","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}
{"title":"Biochemical and proteomic insights into sarcoplasmic reticulum Ca<sup>2+</sup>-ATPase complexes in skeletal muscles.","authors":"Paul Dowling, Dieter Swandulla, Kay Ohlendieck","doi":"10.1080/14789450.2023.2255743","DOIUrl":"10.1080/14789450.2023.2255743","url":null,"abstract":"<p><strong>Introduction: </strong>Skeletal muscles contain large numbers of high-molecular-mass protein complexes in elaborate membrane systems. Integral membrane proteins are involved in diverse cellular functions including the regulation of ion handling, membrane homeostasis, energy metabolism and force transmission.</p><p><strong>Areas covered: </strong>The proteomic profiling of membrane proteins and large protein assemblies in skeletal muscles are outlined in this article. This includes a critical overview of the main biochemical separation techniques and the mass spectrometric approaches taken to study membrane proteins. As an illustrative example of an analytically challenging large protein complex, the proteomic detection and characterization of the Ca<sup>2+</sup>-ATPase of the sarcoplasmic reticulum is discussed. The biological role of this large protein complex during normal muscle functioning, in the context of fiber type diversity and in relation to mechanisms of physiological adaptations and pathophysiological abnormalities is evaluated from a proteomics perspective.</p><p><strong>Expert opinion: </strong>Mass spectrometry-based muscle proteomics has decisively advanced the field of basic and applied myology. Although it is technically challenging to study membrane proteins, innovations in protein separation methodology in combination with sensitive mass spectrometry and improved systems bioinformatics has allowed the detailed proteomic detection and characterization of skeletal muscle membrane protein complexes, such as Ca<sup>2+</sup>-pump proteins of the sarcoplasmic reticulum.</p>","PeriodicalId":50463,"journal":{"name":"Expert Review of Proteomics","volume":" ","pages":"125-142"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166439","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}