Expert Review of Proteomics最新文献

Introduction: The introduction of trapped ion mobility spectrometry (TIMS) in combination with fast high-resolution time-of-flight (TOF) mass spectrometry to the proteomics field led to a jump in protein identifications and quantifications, as well as a lowering of the limit of detection for proteins from biological samples. Parallel Accumulation-Serial Fragmentation (PASEF) is a driving force for this development and has been adapted to discovery as well as targeted proteomics.

Areas covered: Over the last decade, the PASEF concept has been optimized and led to the implementation of eleven new measurement techniques. In this review, we describe all currently described PASEF measurement techniques and their application to clinical proteomics. Literature was searched using PubMed and Google Scholar search engines.

Expert opinion: The use of a dual TIMS tunnel has revolutionized the depth and the speed of proteomics measurements. Currently, we witness how this technique is pushing clinical proteomics forward.

Introduction: Metaproteomics offers insights into the function of complex microbial communities, while it is also capable of revealing microbe-microbe and host-microbe interactions. Data-independent acquisition (DIA) mass spectrometry is an emerging technology, which holds great potential to achieve deep and accurate metaproteomics with higher reproducibility yet still facing a series of challenges due to the inherent complexity of metaproteomics and DIA data.

Areas covered: This review offers an overview of the DIA metaproteomics approaches, covering aspects such as database construction, search strategy, and data analysis tools. Several cases of current DIA metaproteomics studies are presented to illustrate the procedures. Important ongoing challenges are also highlighted. Future perspectives of DIA methods for metaproteomics analysis are further discussed. Cited references are searched through and collected from Google Scholar and PubMed.

Expert opinion: Considering the inherent complexity of DIA metaproteomics data, data analysis strategies specifically designed for interpretation are imperative. From this point of view, we anticipate that deep learning methods and de novo sequencing methods will become more prevalent in the future, potentially improving protein coverage in metaproteomics. Moreover, the advancement of metaproteomics also depends on the development of sample preparation methods, data analysis strategies, etc. These factors are key to unlocking the full potential of metaproteomics.

Introduction: Kidney transplantation significantly improves the lives of those with end-stage kidney disease, offering best alternative to dialysis. However, transplant success is threatened by the acute and chronic rejection mechanisms due to complex immune responses against the new organ.

Areas covered: The ongoing research into biomarkers holds promise for revolutionizing the early detection and monitoring of the graft health. Liquid biopsy techniques offer a new avenue, with several diagnostic, predictive, and prognostic biomarkers showing promise in detecting and monitoring kidney diseases and an early and chronic allograft rejection.

Expert opinion: Evaluating the protein composition related to kidney transplant results could lead to identifying biomarkers that provide insights into the graft functionality. Non-invasive proteomic biomarkers can drastically enhance clinical outcomes and change the way how kidney transplants are evaluated for patients and physicians if they succeed in this transition. Hence, the advancement in proteomic technologies, leads toward a significant improvement in understanding of the protein markers and molecular mechanisms linked to the outcomes of kidney transplants. However, the road from discovery to the use of such proteins in clinical practice is long, with a need for continuous validation and beyond the singular research team with comprehensive infrastructure and across research groups collaboration.

Introduction: Dengue virus (DENV) infection remains one of the most significant infectious diseases in humans. Several efforts have been made to address its molecular mechanisms. Over the last 10 years, proteomics has been widely applied to investigate various aspects of DENV infection.

Areas covered: In this review, we briefly introduce common proteomics approaches using various mass spectrometric modalities followed by summarizing all the discoveries obtained from proteomic investigations of DENV infection over the last 10 years. These include the data on DENV-vector interactions and host responses to address the DENV biology and disease mechanisms. Moreover, applications of proteomics to disease prevention, diagnosis, vaccine design, development of anti-DENV agents and other new treatment strategies are discussed.

Expert opinion: Despite efforts on disease prevention, DENV infection is still a significant global healthcare burden that affects the general population. As summarized herein, proteomic technologies with high-throughput capabilities have provided more in-depth details of protein dynamics during DENV infection. More extensive applications of proteomics and other powerful research tools would provide a promise to better cope and prevent this mosquito-borne infectious disease.

Introduction: Oral squamous cell carcinoma (OSCC) represents the most prevalent form of oral cancer. Potentially malignant disorders of oral mucosa exhibit an elevated propensity for malignant progression. A substantial proportion of cases are discerned during advanced stages, significantly impacting overall survival. This investigation aims to ascertain salivary metabolites with potential utility in the early detection of OSCC.

Methods: A search encompassing PubMed, EMBASE, Scopus, Ovid, Science Direct, and Web of Science databases was conducted to identify eligible articles. The search strategy employed precise terms. The quality assessment of the included studies was executed using the QUADAS 2 ROB tool. This was registered with PROSPERO CRD42021278217.

Results: Upon removing duplicate articles and publications that didn't satisfy the inclusion criteria, seven articles were included in the current study. The Random Effects Maximum Likelihood (REML) model adopted for quantitative synthesis identified Nacetyl glucosamine as the sole metabolite in two studies included in this metaanalysis. The pathways significantly influenced by these identified metabolites were delineated.

Conclusion: This study highlights Nacetyl glucosamine as a distinctive metabolite with the potential to serve as an early diagnostic marker for OSCC. Nevertheless, further research is warranted to validate its clinical utility.

Introduction: Regenerative myogenesis plays a crucial role in mature myofibers to counteract muscular injury or dysfunction due to neuromuscular disorders. The activation of specialized myogenic stem cells, called satellite cells, is intrinsically involved in proliferation and differentiation, followed by myoblast fusion and the formation of multi-nucleated myofibers.

Areas covered: This report provides an overview of the role of satellite cells in the neuromuscular system and the potential future impact of proteomic analyses for biomarker discovery, as well as the identification of novel therapeutic targets in muscle disease. The article reviews the ways in which the systematic analysis of satellite cells, myoblasts and myocytes by single cell proteomics can help to better understand the process of myofiber regeneration.

Expert opinion: In order to better comprehend satellite cell dysfunction in neuromuscular disorders, mass spectrometry-based proteomics is an excellent large-scale analytical tool for the systematic profiling of pathophysiological processes. The optimized isolation of muscle-derived cells can be routinely performed by mechanical/enzymatic dissociation protocols, followed by fluorescence-activated cell sorting in specialized flow cytometers. Ultrasensitive single cell proteomics using label-free quantitation methods or approaches that utilize tandem mass tags are ideal bioanalytical approaches to study the pathophysiological role of stem cells in neuromuscular disease.

Introduction: Atopic Dermatitis (AD) is the most common inflammatory skin disease with a complex and multifactorial pathogenesis. The use of proteomics in understanding AD has yielded the discovery of novel biomarkers and may further expand therapeutic options.

Areas covered: This review summarizes the most recent proteomic studies and the methodologies used in AD. It describes novel biomarkers that may monitor disease course and therapeutic response. The review also highlights skin and blood biomarkers characterizing different AD phenotypes and differentiates AD from other inflammatory skin disorders. A literature search was conducted by querying Scopus, Google Scholar, Pubmed/Medline, and Clinicaltrials.gov up to June 2023.

Expert opinion: The integration of proteomics into research efforts in atopic dermatitis has broadened our understanding of the molecular profile of AD through the discovery of new biomarkers. In addition, proteomics may contribute to the development of targeted treatments ultimately improving personalized medicine. An increasing number of studies are utilizing proteomics to explore this heterogeneous disease.

Introduction: The pharmaceutical industry continues to expand its search for innovative biotherapeutics. The comprehensive characterization of such therapeutics requires many analytical techniques to fully evaluate critical quality attributes, making analysis a bottleneck in discovery and development timelines. While thorough characterization is crucial for ensuring the safety and efficacy of biotherapeutics, there is a need to further streamline analytical characterization and expedite the overall timeline from discovery to market.

Areas covered: This review focuses on recent developments in liquid-phase separations coupled with ion mobility-mass spectrometry (IM-MS) for the development and characterization of biotherapeutics. We cover uses of IM-MS to improve the characterization of monoclonal antibodies, antibody-drug conjugates, host cell proteins, glycans, and nucleic acids. This discussion is based on an extensive literature search using Web of Science, Google Scholar, and SciFinder.

Expert opinion: IM-MS has the potential to enhance the depth and efficiency of biotherapeutic characterization by providing additional insights into conformational changes, post-translational modifications, and impurity profiles. The rapid timescale of IM-MS positions it well to enhance the information content of existing assays through its facile integration with standard liquid-phase separation techniques that are commonly used for biopharmaceutical analysis.

Introduction: The proactive identification of diseases through screening tests has long been endorsed as a means to preempt symptomatic onset. However, such screening endeavors are fraught with complications, such as diagnostic inaccuracies, procedural risks, and patient unease during examinations. These challenges are amplified when screenings for multiple diseases are administered concurrently. Selected Reaction Monitoring (SRM) offers a unique advantage, allowing for the high-throughput quantification of hundreds of analytes with minimal interferences.

Areas covered: Our research posits that SRM-based assays, traditionally tailored for single-disease biomarker profiling, can be repurposed for multi-disease screening. This innovative approach has the potential to substantially alleviate time, labor, and cost demands on healthcare systems and patients alike. Nonetheless, there are formidable methodological hurdles to overcome. These include difficulties in detecting low-abundance proteins and the risk of model overfitting due to the multiple functionalities of single proteins across different disease spectrums - issues especially pertinent in blood-based assays where detection sensitivity is constrained. As we move forward, technological strides in sample preparation, online extraction, throughput, and automation are expected to ameliorate these limitations.

Expert opinion: The maturation of mass spectrometry's integration into clinical laboratories appears imminent, positioning it as an invaluable asset for delivering highly sensitive, reproducible, and precise diagnostic results.