Expert Review of Proteomics最新文献

Introduction: The lysosome is the main degradative organelle of almost all mammalian cells, fulfilling important functions in macromolecule recycling, metabolism, and signaling. Lysosomal dysfunction is connected to a continuously growing number of pathologic conditions, and lysosomal proteins present potential biomarkers for a variety of diseases. Therefore, there is an increasing interest in their analysis in patient samples.

Areas covered: We provide an overview of OMICs studies which identified lysosomal proteins as potential biomarkers for pathological conditions, covering proteomics, genomics, and transcriptomics approaches, identified through PubMed searches. With respect to discovery proteomics analyses, mainly lysosomal luminal and associated proteins were detected, while membrane proteins were found less frequently. Comprehensive coverage of the lysosomal proteome was only achieved by ultra-deep-coverage studies, but targeted approaches allowed for the reproducible quantification of lysosomal proteins in diverse sample types.

Expert opinion: The low abundance of lysosomal proteins complicates their reproducible analysis in patient samples. Whole proteome shotgun analyses fail in many instances to cover the lysosomal proteome, which is due to under-sampling and/or a lack of sensitivity. With the current state of the art, targeted proteomics assays provide the best performance for the characterization of lysosomal proteins in patient samples.

Introduction: The creation of ProteomeXchange data workflows in 2012 transformed the field of proteomics, consisting of the standardization of data submission and dissemination and enabling the widespread reanalysis of public MS proteomics data worldwide. ProteomeXchange has triggered a growing trend toward public dissemination of proteomics data, facilitating the assessment, reuse, comparative analyses, and extraction of new findings from public datasets. By 2022, the consortium is integrated by PRIDE, PeptideAtlas, MassIVE, jPOST, iProX, and Panorama Public.

Areas covered: Here, we review and discuss the current ecosystem of resources, guidelines, and file formats for proteomics data dissemination and reanalysis. Special attention is drawn to new exciting quantitative and post-translational modification-oriented resources. The challenges and future directions on data depositions including the lack of metadata and cloud-based and high-performance software solutions for fast and reproducible reanalysis of the available data are discussed.

Expert opinion: The success of ProteomeXchange and the amount of proteomics data available in the public domain have triggered the creation and/or growth of other protein knowledgebase resources. Data reuse is a leading, active, and evolving field; supporting the creation of new formats, tools, and workflows to rediscover and reshape the public proteomics data.

Introduction: The peritoneum, pleura, and pericardium are yet understudied multicellular systems where mesothelial cells (MCs) and endothelial cells (ECs) are in close proximity. Crosstalk between these cell types likely plays role in molecular transport, immunological reactions, and metabolic processes in health, disease, and therapeutic intervention.

Areas covered: In this review, we discuss recent proteomic efforts to characterize the crosstalk between MC and EC. We describe the proteomic methods necessary for investigation of crosstalk between MC and EC, as well as the in-vitro models that can be employed. Potential experimental approaches range from conditioned medium, via co-culture on semi-permeable membranes, to 3D cell culture based organoid models. While the biological and clinical relevance of the models may increase with their ability to mimic close cell communication, the practicality of these complex experiments corresponds vice versa, making standardization more difficult and expensive.

Expert opinion: Currently, data and reports on mesothelial-to-endothelial crosstalk are still very scarce. In our opinion, the in-vitro model using semi-permeable cell culture inserts will allow to establish a basic understanding of cellular crosstalk that may occur between those cell types. Later-on, more sophisticated 3D cell cultures may be better able to simulate the transport dynamics within the peritoneal membrane.

Introduction: Chronic obstructive pulmonary disease (COPD) was the third leading cause of global death in 2019, causing a huge economic burden to society. Therefore, it is urgent to identify specific phenotypes of COPD patients through early detection, and to promptly treat exacerbations. The field of phosphoproteomics has been a massive advancement, compelled by the developments in mass spectrometry, enrichment strategies, algorithms, and tools. Modern mass spectrometry-based phosphoproteomics allows understanding of disease pathobiology, biomarker discovery, and predicting new therapeutic modalities.

Areas covered: In this article, we present an overview of phosphoproteomic research and strategies for enrichment and fractionation of phosphopeptides, identification of phosphorylation sites, chromatographic separation and mass spectrometry detection strategies, and the potential application of phosphorylated proteomic analysis in the diagnosis, treatment, and prognosis of COPD disease.

Expert opinion: The role of phosphoproteomics in COPD is critical for understanding disease pathobiology, identifying potential biomarkers, and predicting new therapeutic approaches. However, the complexity of COPD requires the more comprehensive understanding that can be achieved through integrated multi-omics studies. Phosphoproteomics, as a part of these multi-omics approaches, can provide valuable insights into the underlying mechanisms of COPD.

The 13^th annual Canadian National Proteomics Network was held in May 2022 in Montreal, Quebec, Canada. More than 175 individuals participated in this dynamic and productive meeting either in-person or virtually. A pre-symposium organized by trainees and dedicated to highlighting the best and brightest emerging talent in proteomics across Canada preceded the main symposium, which welcomed plenary and invited speakers from around the world. The presentations covering ground-breaking science were interspersed with critical discussions on improving equity, diversity, and inclusion within the proteomics community across Canada, along with important networking opportunities for early-career researchers.

Background: Many stage II/III colorectal cancer (CRC) patients may relapse after routine treatments. Aberrant phosphorylation can regulate pathophysiological processes of tumors, and finding characteristic protein phosphorylation is an efficient approach for the prediction of CRC relapse.

Research design and methods: We compared the tissue proteome and phosphoproteome of stage II/III CRC patients between the relapsed group (n = 5) and the non-relapsed group (n = 5). Phosphopeptides were enriched with Ti⁴⁺-IMAC material. We utilized label-free quantification-based proteomics to screen differentially expressed proteins and phosphopeptides between the two groups. Gene Ontology (GO) analysis and Ingenuity Pathway Analysis (IPA) were used for bioinformatics analysis.

Results: The immune response of the relapsed group (Z-score -2.229) was relatively poorer than that of the non-relapsed group (Z-score 1.982), while viability of tumor was more activated (Z-score 2.895) in the relapsed group, which might cause increased relapse risk. The phosphorylation degrees of three phosphosites (phosphosite 1362 of TP53BP1, phosphosite 809 of VCL and phosphosite 438 of STK10) might be reliable prognostic biomarkers.

Conclusions: Some promising proteins and phosphopeptides were discovered to predict the relapse risk in postoperative follow-ups.

Introduction: Insights into the mechanisms of protein homeostasis and proteasomal degradation have led to new strategies of redirecting the ubiquitin-proteasome system (UPS) to reduce or eliminate proteins or survival factors key to malignant pathobiology, multiple myeloma (MM) in particular. These strategies have enabled researchers to target proteins that were previously considered difficult to modulate by pharmacological means.

Areas covered: This review provides a brief overview of UPS biology, particularly the role of the CRL4^CRBN E3 ubiquitin ligase complex, and summarizes current strategies for co-opting the UPS, including CELMoD compounds, SNIPERs, PROTACs, and degronimids. A detailed discussion is provided on lead CELMoD compounds iberdomide and mezigdomide, which are currently being evaluated in clinical trials in patients with MM.

Expert opinion: Since a high proportion of patients develop drug resistance, it is vital to have novel therapeutic agents for treating relapsed patients with MM more effectively. It is encouraging that the expanding pathophysiological insight into cellular signaling pathways in MM increasingly translates into the development of novel therapeutic agents such as targeted protein degraders. This holds promise for improving outcomes in MM and beyond.