Proteomes

12 pages, 879 KiB

Open AccessArticle

Investigating the Prognostic Potential of Plasma ST2 in Patients with Peripheral Artery Disease: Identification and Evaluation

by Ben Li, Farah Shaikh, Abdelrahman Zamzam, Rawand Abdin and Mohammad Qadura

Proteomes 2024, 12(3), 24; https://doi.org/10.3390/proteomes12030024 - 29 Aug 2024

Abstract

Soluble interleukin 1 receptor-like 1 (ST2) is a circulating protein demonstrated to be associated with cardiovascular diseases; however, it has not been studied as a biomarker for peripheral artery disease (PAD). Using a prospectively recruited cohort of 476 patients (312 with PAD and [...] Read more.

Soluble interleukin 1 receptor-like 1 (ST2) is a circulating protein demonstrated to be associated with cardiovascular diseases; however, it has not been studied as a biomarker for peripheral artery disease (PAD). Using a prospectively recruited cohort of 476 patients (312 with PAD and 164 without PAD), we conducted a prognostic study of PAD using clinical/biomarker data. Plasma concentrations of three circulating proteins [ST2, cytokine-responsive gene-2 (CRG-2), vascular endothelial growth factor (VEGF)] were measured at baseline and the cohort was followed for 2 years. The outcome of interest was a 2-year major adverse limb event (MALE; composite of major amputation, vascular intervention, or acute limb ischemia). Using 10-fold cross-validation, a random forest model was trained using clinical characteristics and plasma ST2 levels. The primary model evaluation metric was the F1 score. Out of the three circulating proteins analyzed, ST2 was the only one that was statistically significantly higher in individuals with PAD compared to patients without PAD (mean concentration in plasma of 9.57 [SD 5.86] vs. 11.39 [SD 6.43] pg/mL, p < 0.001). Over a 2-year period, 28 (9%) patients with PAD experienced MALE. Our predictive model, incorporating clinical features and plasma ST2 levels, achieved an F1 score of 0.713 for forecasting 2-year MALE outcomes. Patients identified as high-risk by this model showed a significantly increased likelihood of developing MALE (HR 1.06, 95% CI 1.02–1.13, p = 0.003). By combining clinical characteristics and plasma ST2 levels, our proposed predictive model offers accurate risk assessment for 2-year MALE in PAD patients. This algorithm supports risk stratification in PAD, guiding clinical decisions regarding further vascular evaluation, specialist referrals, and appropriate medical or surgical interventions, thereby potentially enhancing patient outcomes. Full article

(This article belongs to the Section Identification of Potential Biomarkers and Potential Therapeutic Targets)

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31 pages, 1404 KiB

Open AccessReview

The Current Molecular and Cellular Landscape of Chronic Obstructive Pulmonary Disease (COPD): A Review of Therapies and Efforts towards Personalized Treatment

by Luke A. Farrell, Matthew B. O’Rourke, Matthew P. Padula, Fernando Souza-Fonseca-Guimaraes, Gaetano Caramori, Peter A. B. Wark, Shymali C. Dharmage and Phillip M. Hansbro

Proteomes 2024, 12(3), 23; https://doi.org/10.3390/proteomes12030023 - 16 Aug 2024

Abstract

Chronic obstructive pulmonary disease (COPD) ranks as the third leading cause of global illness and mortality. It is commonly triggered by exposure to respiratory irritants like cigarette smoke or biofuel pollutants. This multifaceted condition manifests through an array of symptoms and lung irregularities, [...] Read more.

Chronic obstructive pulmonary disease (COPD) ranks as the third leading cause of global illness and mortality. It is commonly triggered by exposure to respiratory irritants like cigarette smoke or biofuel pollutants. This multifaceted condition manifests through an array of symptoms and lung irregularities, characterized by chronic inflammation and reduced lung function. Present therapies primarily rely on maintenance medications to alleviate symptoms, but fall short in impeding disease advancement. COPD’s diverse nature, influenced by various phenotypes, complicates diagnosis, necessitating precise molecular characterization. Omics-driven methodologies, including biomarker identification and therapeutic target exploration, offer a promising avenue for addressing COPD’s complexity. This analysis underscores the critical necessity of improving molecular profiling to deepen our comprehension of COPD and identify potential therapeutic targets. Moreover, it advocates for tailoring treatment strategies to individual phenotypes. Through comprehensive exploration-based molecular characterization and the adoption of personalized methodologies, innovative treatments may emerge that are capable of altering the trajectory of COPD, instilling optimism for efficacious disease-modifying interventions. Full article

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17 pages, 2636 KiB

Open AccessArticle

The Low-Abundance Plasma Proteome Reveals Differentially Abundant Proteins Associated with Breast Implant Capsular Contracture: A Pilot Study

by Md. Arifur Rahman, Ardeshir Amirkhani, Maria Mempin, Seong Beom Ahn, Anand K. Deva, Mark S. Baker, Karen Vickery and Honghua Hu

Proteomes 2024, 12(3), 22; https://doi.org/10.3390/proteomes12030022 - 6 Aug 2024

Abstract

Capsular contracture (CC) is one of the most common postoperative complications associated with breast implant-associated infections. The mechanisms that lead to CC remain poorly understood. Plasma is an ideal biospecimen for early proteomics biomarker discovery. However, as high-abundance proteins mask signals from low-abundance [...] Read more.

Capsular contracture (CC) is one of the most common postoperative complications associated with breast implant-associated infections. The mechanisms that lead to CC remain poorly understood. Plasma is an ideal biospecimen for early proteomics biomarker discovery. However, as high-abundance proteins mask signals from low-abundance proteins, identifying novel or specific proteins as biomarkers for a particular disease has been hampered. Here, we employed depletion of high-abundance plasma proteins followed by Tandem Mass Tag (TMT)-based quantitative proteomics to compare 10 healthy control patients against 10 breast implant CC patients. A total of 450 proteins were identified from these samples. Among them, 16 proteins were significantly differentially expressed in which 5 proteins were upregulated and 11 downregulated in breast implant CC patients compared to healthy controls. Gene Ontology enrichment analysis revealed that proteins related to cell, cellular processes and catalytic activity were highest in the cellular component, biological process, and molecular function categories, respectively. Further, pathway analysis revealed that inflammatory responses, focal adhesion, platelet activation, and complement and coagulation cascades were enriched pathways. The differentially abundant proteins from TMT-based quantitative proteomics have the potential to provide important information for future mechanistic studies and in the development of breast implant CC biomarkers. Full article

(This article belongs to the Section Identification of Potential Biomarkers and Potential Therapeutic Targets)

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8 pages, 718 KiB

Open AccessArticle

Quantitative Analysis of Complement Membrane Attack Complex Proteins Associated with Extracellular Vesicles

by Illarion V. Turko

Proteomes 2024, 12(3), 21; https://doi.org/10.3390/proteomes12030021 - 12 Jul 2024

Abstract

Extracellular vesicles (EVs) represent a universal mechanism of intercellular communication in normal and pathological conditions. There are reports showing the presence of complement proteins in EV preparations, specifically those that can form a membrane attack complex (MAC). In the present work, we have [...] Read more.

Extracellular vesicles (EVs) represent a universal mechanism of intercellular communication in normal and pathological conditions. There are reports showing the presence of complement proteins in EV preparations, specifically those that can form a membrane attack complex (MAC). In the present work, we have used a quantitative mass spectrometry method that allows for the measurement of multiple targeted proteins in one experimental run. The quantification of MAC-forming proteins, namely C5b, C6, C7, C8, and C9, in highly purified EVs from normal human plasma revealed the presence of MAC proteins at approximately equal stoichiometry that does not fit the expected stoichiometry of preformed MAC. We concluded that while MAC proteins can be associated with EVs from normal plasma and presumably can be delivered to the recipient cells, there is no evidence that the EVs carry preformed MAC. Full article

(This article belongs to the Section Extracellular Vesicles)

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17 pages, 6479 KiB

Open AccessArticle

Seasonal Proteome Variations in Orbicella faveolata Reveal Molecular Thermal Stress Adaptations

by Martha Ricaurte, Nikolaos V. Schizas, Ernesto F. Weil, Pawel Ciborowski and Nawal M. Boukli

Proteomes 2024, 12(3), 20; https://doi.org/10.3390/proteomes12030020 - 10 Jul 2024

Abstract

Although seasonal water temperatures typically fluctuate by less than 4 °C across most tropical reefs, sustained heat stress with an increase of even 1 °C can alter and destabilize metabolic and physiological coral functions, leading to losses of coral reefs worldwide. The Caribbean [...] Read more.

Although seasonal water temperatures typically fluctuate by less than 4 °C across most tropical reefs, sustained heat stress with an increase of even 1 °C can alter and destabilize metabolic and physiological coral functions, leading to losses of coral reefs worldwide. The Caribbean region provides a natural experimental design to study how corals respond physiologically throughout the year. While characterized by warm temperatures and precipitation, there is a significant seasonal component with relative cooler and drier conditions during the months of January to February and warmer and wetter conditions during September and October. We conducted a comparative abundance of differentially expressed proteins with two contrasting temperatures during the cold and warm seasons of 2014 and 2015 in Orbicella faveolata, one of the most important and affected reef-building corals of the Caribbean. All presented proteoforms (42) were found to be significant in our proteomics differential expression analysis and classified based on their gene ontology. The results were accomplished by a combination of two-dimensional gel electrophoresis (2DE) to separate and visualize proteins and mass spectrometry (MS) for protein identification. To validate the differentially expressed proteins of Orbicella faveolata at the transcription level, qRT-PCR was performed. Our data indicated that a 3.1 °C increase in temperature in O. faveolata between the cold and warm seasons in San Cristobal and Enrique reefs of southwestern Puerto Rico was enough to affect the expression of a significant number of proteins associated with oxidative and heat stress responses, metabolism, immunity, and apoptosis. This research extends our knowledge into the mechanistic response of O. faveolata to mitigate thermal seasonal temperature variations in coral reefs. Full article

(This article belongs to the Section Proteoform Analysis (Top-Down and Bottom-Up))

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1 pages, 131 KiB

Open AccessCorrection

Correction: Jain et al. Proteomic Approach for Comparative Analysis of the Spike Protein of SARS-CoV-2 Omicron (B.1.1.529) Variant and Other Pango Lineages. Proteomes 2022, 10, 34

by Mukul Jain, Nil Patil, Darshil Gor, Mohit Kumar Sharma, Neha Goel and Prashant Kaushik

Proteomes 2024, 12(3), 19; https://doi.org/10.3390/proteomes12030019 - 9 Jul 2024

Abstract

In the publication [...] Full article

20 pages, 6013 KiB

Open AccessArticle

Investigating and Annotating the Human Peptidome Profile from Urine under Normal Physiological Conditions

by Amr Elguoshy, Keiko Yamamoto, Yoshitoshi Hirao, Tomohiro Uchimoto, Kengo Yanagita and Tadashi Yamamoto

Proteomes 2024, 12(3), 18; https://doi.org/10.3390/proteomes12030018 - 25 Jun 2024

Abstract

Examining the composition of the typical urinary peptidome and identifying the enzymes responsible for its formation holds significant importance, as it mirrors the normal physiological state of the human body. Any deviation from this normal profile could serve as an indicator of pathological [...] Read more.

Examining the composition of the typical urinary peptidome and identifying the enzymes responsible for its formation holds significant importance, as it mirrors the normal physiological state of the human body. Any deviation from this normal profile could serve as an indicator of pathological processes occurring in vivo. Consequently, this study focuses on characterizing the normal urinary peptidome and investigating the various catalytic enzymes that are involved in generating these native peptides in urine. Our findings reveal that 1503 endogenous peptides, corresponding to 436 precursor proteins, were consistently identified robustly in at least 10 samples out of a total of 19 samples. Notably, the liver and kidneys exhibited the highest number of tissue-enriched or enhanced genes in the analyzed urinary peptidome. Furthermore, among the catalytic types, CTSD (cathepsin D) and MMP2 (matrix metalloproteinase-2) emerged as the most prominent peptidases in the aspartic and metallopeptidases categories, respectively. A comparison of our dataset with two of the most comprehensive urine peptidome datasets to date indicates a consistent relative abundance of core endogenous peptides for different proteins across all three datasets. These findings can serve as a foundational reference for the discovery of biomarkers in various human diseases. Full article

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17 pages, 575 KiB

Open AccessReview

The Current State of Proteomics and Metabolomics for Inner Ear Health and Disease

by Motahare Khorrami, Christopher Pastras, Paul A. Haynes, Mehdi Mirzaei and Mohsen Asadnia

Proteomes 2024, 12(2), 17; https://doi.org/10.3390/proteomes12020017 - 4 Jun 2024

Abstract

Characterising inner ear disorders represents a significant challenge due to a lack of reliable experimental procedures and identified biomarkers. It is also difficult to access the complex microenvironments of the inner ear and investigate specific pathological indicators through conventional techniques. Omics technologies have [...] Read more.

Characterising inner ear disorders represents a significant challenge due to a lack of reliable experimental procedures and identified biomarkers. It is also difficult to access the complex microenvironments of the inner ear and investigate specific pathological indicators through conventional techniques. Omics technologies have the potential to play a vital role in revolutionising the diagnosis of ear disorders by providing a comprehensive understanding of biological systems at various molecular levels. These approaches reveal valuable information about biomolecular signatures within the cochlear tissue or fluids such as the perilymphatic and endolymphatic fluid. Proteomics identifies changes in protein abundance, while metabolomics explores metabolic products and pathways, aiding the characterisation and early diagnosis of diseases. Although there are different methods for identifying and quantifying biomolecules, mass spectrometry, as part of proteomics and metabolomics analysis, could be utilised as an effective instrument for understanding different inner ear disorders. This study aims to review the literature on the application of proteomic and metabolomic approaches by specifically focusing on Meniere’s disease, ototoxicity, noise-induced hearing loss, and vestibular schwannoma. Determining potential protein and metabolite biomarkers may be helpful for the diagnosis and treatment of inner ear problems. Full article

(This article belongs to the Special Issue Quantitative Proteomics: Techniques and Applications)

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19 pages, 9666 KiB

Open AccessArticle

Plasma and Kidney Proteome Profiling Combined with Laser Capture Microdissection Reveal Large Increases in Immunoglobulins with Age

by Leanne J. G. Chan, Niclas Olsson, Magdalena Preciado López, Kayley Hake, Haruna Tomono, Matthew A. Veras and Fiona E. McAllister

Proteomes 2024, 12(2), 16; https://doi.org/10.3390/proteomes12020016 - 3 Jun 2024

Abstract

One of the main hallmarks of aging is aging-associated inflammation, also known as inflammaging. In this study, by comparing plasma and kidney proteome profiling of young and old mice using LC–MS profiling, we discovered that immunoglobulins are the proteins that exhibit the highest [...] Read more.

One of the main hallmarks of aging is aging-associated inflammation, also known as inflammaging. In this study, by comparing plasma and kidney proteome profiling of young and old mice using LC–MS profiling, we discovered that immunoglobulins are the proteins that exhibit the highest increase with age. This observation seems to have been disregarded because conventional proteome profiling experiments typically overlook the expression of high-abundance proteins or employ depletion methods to remove them before LC–MS analysis. We show that proteome profiling of immunoglobulins will likely be a useful biomarker of aging. Spatial profiling using immunofluorescence staining of kidney sections indicates that the main increases in immunoglobulins with age are localized in the glomeruli of the kidney. Using laser capture microdissection coupled with LC–MS, we show an increase in multiple immune-related proteins in glomeruli from aged mice. Increased deposition of immunoglobulins, immune complexes, and complement proteins in the kidney glomeruli may be a factor leading to reduced filtering capacity of the kidney with age. Therapeutic strategies to reduce the deposition of immunoglobulins in the kidney may be an attractive strategy for healthy aging. Full article

(This article belongs to the Special Issue Quantitative Proteomics: Techniques and Applications)

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15 pages, 2884 KiB

Open AccessPerspective

Puzzle of Proteoform Variety—Where Is a Key?

by Stanislav Naryzhny

Proteomes 2024, 12(2), 15; https://doi.org/10.3390/proteomes12020015 - 10 May 2024

Abstract

One of the human proteome puzzles is an imbalance between the theoretically calculated and experimentally measured amounts of proteoforms. Considering the possibility of combinations of different post-translational modifications (PTMs), the quantity of possible proteoforms is huge. An estimation gives more than a million [...] Read more.

One of the human proteome puzzles is an imbalance between the theoretically calculated and experimentally measured amounts of proteoforms. Considering the possibility of combinations of different post-translational modifications (PTMs), the quantity of possible proteoforms is huge. An estimation gives more than a million different proteoforms in each cell type. But, it seems that there is strict control over the production and maintenance of PTMs. Although the potential complexity of proteoforms due to PTMs is tremendous, available information indicates that only a small part of it is being implemented. As a result, a protein could have many proteoforms according to the number of modification sites, but because of different systems of personal regulation, the profile of PTMs for a given protein in each organism is slightly different. Full article

(This article belongs to the Special Issue 10th Anniversary of Proteomes—Reviewing the Progress and Prospects of Proteomics)

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24 pages, 412 KiB

Open AccessPerspective

Proteomics—The State of the Field: The Definition and Analysis of Proteomes Should Be Based in Reality, Not Convenience

by Jens R. Coorssen and Matthew P. Padula

Proteomes 2024, 12(2), 14; https://doi.org/10.3390/proteomes12020014 - 19 Apr 2024

Cited by 1

Abstract

With growing recognition and acknowledgement of the genuine complexity of proteomes, we are finally entering the post-proteogenomic era. Routine assessment of proteomes as inferred correlates of gene sequences (i.e., canonical ‘proteins’) cannot provide the necessary critical analysis of systems-level biology that is needed [...] Read more.

With growing recognition and acknowledgement of the genuine complexity of proteomes, we are finally entering the post-proteogenomic era. Routine assessment of proteomes as inferred correlates of gene sequences (i.e., canonical ‘proteins’) cannot provide the necessary critical analysis of systems-level biology that is needed to understand underlying molecular mechanisms and pathways or identify the most selective biomarkers and therapeutic targets. These critical requirements demand the analysis of proteomes at the level of proteoforms/protein species, the actual active molecular players. Currently, only highly refined integrated or integrative top-down proteomics (iTDP) enables the analytical depth necessary to provide routine, comprehensive, and quantitative proteome assessments across the widest range of proteoforms inherent to native systems. Here we provide a broad perspective of the field, taking in historical and current realities, to establish a more balanced understanding of where the field has come from (in particular during the ten years since Proteomes was launched), current issues, and how things likely need to proceed if necessary deep proteome analyses are to succeed. We base this in our firm belief that the best proteomic analyses reflect, as closely as possible, the native sample at the moment of sampling. We also seek to emphasise that this and future analytical approaches are likely best based on the broad recognition and exploitation of the complementarity of currently successful approaches. This also emphasises the need to continuously evaluate and further optimize established approaches, to avoid complacency in thinking and expectations but also to promote the critical and careful development and introduction of new approaches, most notably those that address proteoforms. Above all, we wish to emphasise that a rigorous focus on analytical quality must override current thinking that largely values analytical speed; the latter would certainly be nice, if only proteoforms could thus be effectively, routinely, and quantitatively assessed. Alas, proteomes are composed of proteoforms, not molecular species that can be amplified or that directly mirror genes (i.e., ‘canonical’). The problem is hard, and we must accept and address it as such, but the payoff in playing this longer game of rigorous deep proteome analyses is the promise of far more selective biomarkers, drug targets, and truly personalised or even individualised medicine. Full article

(This article belongs to the Special Issue 10th Anniversary of Proteomes—Reviewing the Progress and Prospects of Proteomics)

20 pages, 1318 KiB

Open AccessReview

Key Proteomics Tools for Fundamental and Applied Microalgal Research

by Maxence Plouviez and Eric Dubreucq

Proteomes 2024, 12(2), 13; https://doi.org/10.3390/proteomes12020013 - 4 Apr 2024

Cited by 2

Abstract

Microscopic, photosynthetic prokaryotes and eukaryotes, collectively referred to as microalgae, are widely studied to improve our understanding of key metabolic pathways (e.g., photosynthesis) and for the development of biotechnological applications. Omics technologies, which are now common tools in biological research, have been shown [...] Read more.

Microscopic, photosynthetic prokaryotes and eukaryotes, collectively referred to as microalgae, are widely studied to improve our understanding of key metabolic pathways (e.g., photosynthesis) and for the development of biotechnological applications. Omics technologies, which are now common tools in biological research, have been shown to be critical in microalgal research. In the past decade, significant technological advancements have allowed omics technologies to become more affordable and efficient, with huge datasets being generated. In particular, where studies focused on a single or few proteins decades ago, it is now possible to study the whole proteome of a microalgae. The development of mass spectrometry-based methods has provided this leap forward with the high-throughput identification and quantification of proteins. This review specifically provides an overview of the use of proteomics in fundamental (e.g., photosynthesis) and applied (e.g., lipid production for biofuel) microalgal research, and presents future research directions in this field. Full article

(This article belongs to the Special Issue Quantitative Proteomics: Techniques and Applications)

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14 pages, 2613 KiB

Open AccessArticle

Comprehensive Proteome Profiling of a Xanthomonas campestris pv. Campestris B100 Culture Grown in Minimal Medium with a Specific Focus on Nutrient Consumption and Xanthan Biosynthesis

by Ben Struck, Sanne Jitske Wiersma, Vera Ortseifen, Alfred Pühler and Karsten Niehaus

Proteomes 2024, 12(2), 12; https://doi.org/10.3390/proteomes12020012 - 3 Apr 2024

Abstract

Xanthan, a bacterial polysaccharide, is widespread in industrial applications, particularly as a food additive. However, little is known about the process of xanthan synthesis on the proteome level, even though Xanthomonas campestris is frequently used for xanthan fermentation. A label-free LC-MS/MS method was [...] Read more.

Xanthan, a bacterial polysaccharide, is widespread in industrial applications, particularly as a food additive. However, little is known about the process of xanthan synthesis on the proteome level, even though Xanthomonas campestris is frequently used for xanthan fermentation. A label-free LC-MS/MS method was employed to study the protein changes during xanthan fermentation in minimal medium. According to the reference database, 2416 proteins were identified, representing 54.75 % of the proteome. The study examined changes in protein abundances concerning the growth phase and xanthan productivity. Throughout the experiment, changes in nitrate concentration appeared to affect the abundance of most proteins involved in nitrogen metabolism, except Gdh and GlnA. Proteins involved in sugar nucleotide metabolism stay unchanged across all growth phases. Apart from GumD, GumB, and GumC, the gum proteins showed no significant changes throughout the experiment. GumD, the first enzyme in the assembly of the xanthan-repeating unit, peaked during the early stationary phase but decreased during the late stationary phase. GumB and GumC, which are involved in exporting xanthan, increased significantly during the stationary phase. This study suggests that a potential bottleneck for xanthan productivity does not reside in the abundance of proteins directly involved in the synthesis pathways. Full article

(This article belongs to the Section Microbial Proteomics)

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15 pages, 3171 KiB

Open AccessArticle

Integration of Urinary Peptidome and Fecal Microbiome to Explore Patient Clustering in Chronic Kidney Disease

by Emmanouil Mavrogeorgis, Sophie Valkenburg, Justyna Siwy, Agnieszka Latosinska, Griet Glorieux, Harald Mischak and Joachim Jankowski

Proteomes 2024, 12(2), 11; https://doi.org/10.3390/proteomes12020011 - 1 Apr 2024

Abstract

Millions of people worldwide currently suffer from chronic kidney disease (CKD), requiring kidney replacement therapy at the end stage. Endeavors to better understand CKD pathophysiology from an omics perspective have revealed major molecular players in several sample sources. Focusing on non-invasive sources, gut [...] Read more.

Millions of people worldwide currently suffer from chronic kidney disease (CKD), requiring kidney replacement therapy at the end stage. Endeavors to better understand CKD pathophysiology from an omics perspective have revealed major molecular players in several sample sources. Focusing on non-invasive sources, gut microbial communities appear to be disturbed in CKD, while numerous human urinary peptides are also dysregulated. Nevertheless, studies often focus on isolated omics techniques, thus potentially missing the complementary pathophysiological information that multidisciplinary approaches could provide. To this end, human urinary peptidome was analyzed and integrated with clinical and fecal microbiome (16S sequencing) data collected from 110 Non-CKD or CKD individuals (Early, Moderate, or Advanced CKD stage) that were not undergoing dialysis. Participants were visualized in a three-dimensional space using different combinations of clinical and molecular data. The most impactful clinical variables to discriminate patient groups in the reduced dataspace were, among others, serum urea, haemoglobin, total blood protein, urinary albumin, urinary erythrocytes, blood pressure, cholesterol measures, body mass index, Bristol stool score, and smoking; relevant variables were also microbial taxa, including Roseburia, Butyricicoccus, Flavonifractor, Burkholderiales, Holdemania, Synergistaceae, Enterorhabdus, and Senegalimassilia; urinary peptidome fragments were predominantly derived from proteins of collagen origin; among the non-collagen parental proteins were FXYD2, MGP, FGA, APOA1, and CD99. The urinary peptidome appeared to capture substantial variation in the CKD context. Integrating clinical and molecular data contributed to an improved cohort separation compared to clinical data alone, indicating, once again, the added value of this combined information in clinical practice. Full article

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32 pages, 6256 KiB

Open AccessArticle

Cadmium Highlights Common and Specific Responses of Two Freshwater Sentinel Species, Dreissena polymorpha and Dreissena rostriformis bugensis

by Florence Bultelle, Aimie Le Saux, Elise David, Arnaud Tanguy, Simon Devin, Stéphanie Olivier, Agnès Poret, Philippe Chan, Fanny Louis, Laurence Delahaut, Sandrine Pain-Devin, Romain Péden, David Vaudry, Frank Le Foll and Béatrice Rocher

Proteomes 2024, 12(2), 10; https://doi.org/10.3390/proteomes12020010 - 26 Mar 2024

Abstract

Zebra mussel (ZM), Dreissena polymorpha, commonly used as a sentinel species in freshwater biomonitoring, is now in competition for habitat with quagga mussel (QM), Dreissena rostriformis bugensis. This raises the question of the quagga mussel’s use in environmental survey. To better characterise [...] Read more.

Zebra mussel (ZM), Dreissena polymorpha, commonly used as a sentinel species in freshwater biomonitoring, is now in competition for habitat with quagga mussel (QM), Dreissena rostriformis bugensis. This raises the question of the quagga mussel’s use in environmental survey. To better characterise QM response to stress compared with ZM, both species were exposed to cadmium (100 µg·L⁻¹), a classic pollutant, for 7 days under controlled conditions. The gill proteomes were analysed using two-dimensional electrophoresis coupled with mass spectrometry. For ZM, 81 out of 88 proteoforms of variable abundance were identified using mass spectrometry, and for QM, 105 out of 134. Interestingly, the proteomic response amplitude varied drastically, with 5.6% of proteoforms of variable abundance (DAPs) in ZM versus 9.4% in QM. QM also exhibited greater cadmium accumulation. Only 12 common DAPs were observed. Several short proteoforms were detected, suggesting proteolysis. Functional analysis is consistent with the pleiotropic effects of the toxic metal ion cadmium, with alterations in sulphur and glutathione metabolisms, cellular calcium signalling, cytoskeletal dynamics, energy production, chaperone activation, and membrane events with numerous proteins involved in trafficking and endocytosis/exocytosis processes. Beyond common responses, the sister species display distinct reactions, with cellular response to stress being the main category involved in ZM as opposed to calcium and cytoskeleton alterations in QM. Moreover, QM exhibited greater evidence of proteolysis and cell death. Overall, these results suggest that QM has a weaker stress response capacity than ZM. Full article

(This article belongs to the Special Issue 10th Anniversary of Proteomes—Reviewing the Progress and Prospects of Proteomics)

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14 pages, 768 KiB

Open AccessReview

Proteoform Analysis of the Human Olfactory System: A Window into Neurodegenerative Diseases

by Eqrem Rusi, Fiorenza Pennacchia, Wael Abu Ruqa, Giuseppina Talarico, Giuseppe Bruno, Antonio Minni and Christian Barbato

Proteomes 2024, 12(1), 9; https://doi.org/10.3390/proteomes12010009 - 21 Mar 2024

Abstract

Background: Very little is known about the proteome of the human olfactory system and how diseases associated with olfactory dysfunctions can affect it. With this review, we try to summarize the existing literature on the use of this technique for a better [...] Read more.

Background: Very little is known about the proteome of the human olfactory system and how diseases associated with olfactory dysfunctions can affect it. With this review, we try to summarize the existing literature on the use of this technique for a better understanding of the neurodegenerative disease process. Methods: We used the PubMed database and found different articles which were then selected independently by three authors. Results: We found 157 articles, of which, after careful selection, only 30 were analyzed in this review. We presented all the associations identified between the protein/pathway alterations neurodegenerative diseases and SARS-CoV-2 infection. Conclusions: We think that the proteome of the olfactory system through blood, saliva, and mucus analysis could be a new way to better understand, diagnose, and finally treat neurodegenerative diseases. Full article

(This article belongs to the Topic Proteomics and Metabolomics in Biomedicine, 2nd Volume)

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19 pages, 1241 KiB

Open AccessReview

Biomarkers in Ovarian Cancer: Towards Personalized Medicine

by Carlos López-Portugués, María Montes-Bayón and Paula Díez

Proteomes 2024, 12(1), 8; https://doi.org/10.3390/proteomes12010008 - 18 Mar 2024

Cited by 1

Abstract

Ovarian cancer is one of the deadliest cancers in women. The lack of specific symptoms, especially at the initial stages of disease development, together with the malignancy heterogeneity, lower the life expectancy of patients. Aiming to improve survival rates, diagnostic and prognostic biomarkers [...] Read more.

Ovarian cancer is one of the deadliest cancers in women. The lack of specific symptoms, especially at the initial stages of disease development, together with the malignancy heterogeneity, lower the life expectancy of patients. Aiming to improve survival rates, diagnostic and prognostic biomarkers are increasingly employed in clinics, providing gynecologists and oncologists with new tools to guide their treatment decisions. Despite the vast number of investigations, there is still an urgent need to discover more ovarian cancer subtype-specific markers which could further improve patient classification. To this end, high-throughput screening technologies, like mass spectrometry, are applied to deepen the tumoral cellular landscape and describe the malignant phenotypes. As for disease treatment, new targeted therapies, such as those based on PARP inhibitors, have shown great efficacy in destroying the tumoral cells. Likewise, drug-nanocarrier systems targeting the tumoral cells have exhibited promising results. In this narrative review, we summarize the latest achievements in the pursuit of biomarkers for ovarian cancer and recent anti-tumoral therapies. Full article

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19 pages, 7120 KiB

Open AccessArticle

Quantitative Proteomics Reveal Region-Specific Alterations in Neuroserpin-Deficient Mouse Brain and Retina: Insights into Serpini1 Function

by Shahab Mirshahvaladi, Nitin Chitranshi, Ardeshir Amirkhani, Rashi Rajput, Devaraj Basavarajappa, Roshana Vander Wall, Dana Pascovici, Angela Godinez, Giovanna Galliciotti, Joao A. Paulo, Veer Gupta, Stuart L. Graham, Vivek Gupta and Mehdi Mirzaei

Proteomes 2024, 12(1), 7; https://doi.org/10.3390/proteomes12010007 - 14 Mar 2024

Abstract

Neural regeneration and neuroprotection represent strategies for future management of neurodegenerative disorders such as Alzheimer’s disease (AD) or glaucoma. However, the complex molecular mechanisms that are involved in neuroprotection are not clearly understood. A promising candidate that maintains neuroprotective signaling networks is neuroserpin [...] Read more.

Neural regeneration and neuroprotection represent strategies for future management of neurodegenerative disorders such as Alzheimer’s disease (AD) or glaucoma. However, the complex molecular mechanisms that are involved in neuroprotection are not clearly understood. A promising candidate that maintains neuroprotective signaling networks is neuroserpin (Serpini1), a serine protease inhibitor expressed in neurons which selectively inhibits extracellular tissue-type plasminogen activator (tPA)/plasmin and plays a neuroprotective role during ischemic brain injury. Abnormal function of this protein has been implicated in several conditions including stroke, glaucoma, AD, and familial encephalopathy with neuroserpin inclusion bodies (FENIB). Here, we explore the potential biochemical roles of Serpini1 by comparing proteome changes between neuroserpin-deficient (NS^−/−) and control mice, in the retina (RE), optic nerve (ON), frontal cortex (FC), visual cortex (VC), and cerebellum (CB). To achieve this, a multiple-plex quantitative proteomics approach using isobaric tandem mass tag (TMT) technology was employed followed by functional enrichment and protein–protein interaction analysis. We detected around 5000 proteins in each tissue and a pool of 6432 quantified proteins across all regions, resulting in a pool of 1235 differentially expressed proteins (DEPs). Principal component analysis and hierarchical clustering highlighted similarities and differences in the retina compared to various brain regions, as well as differentiating NS^−/− proteome signatures from control samples. The visual cortex revealed the highest number of DEPs, followed by cerebellar regions. Pathway analysis unveiled region-specific changes, including visual perception, focal adhesion, apoptosis, glutamate receptor activation, and supramolecular fiber organization in RE, ON, FC, VC, and CB, respectively. These novel findings provide comprehensive insights into the region-specific networking of Serpini1 in the central nervous system, further characterizing its potential role as a neuroprotective agent. Data are available via ProteomeXchange with identifier PXD046873. Full article

(This article belongs to the Special Issue Quantitative Proteomics: Techniques and Applications)

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14 pages, 2376 KiB

Open AccessArticle

Observations from the Proteomics Bench

by Simone König, Karin Schork and Martin Eisenacher

Proteomes 2024, 12(1), 6; https://doi.org/10.3390/proteomes12010006 - 6 Feb 2024

Cited by 1

Abstract

Many challenges in proteomics result from the high-throughput nature of the experiments. This paper first presents pre-analytical problems, which still occur, although the call for standardization in omics has been ongoing for many years. This article also discusses aspects that affect bioinformatic analysis [...] Read more.

Many challenges in proteomics result from the high-throughput nature of the experiments. This paper first presents pre-analytical problems, which still occur, although the call for standardization in omics has been ongoing for many years. This article also discusses aspects that affect bioinformatic analysis based on three sets of reference data measured with different orbitrap instruments. Despite continuous advances in mass spectrometer technology as well as analysis software, data-set-wise quality control is still necessary, and decoy-based estimation, although challenged by modern instruments, should be utilized. We draw attention to the fact that numerous young researchers perceive proteomics as a mature, readily applicable technology. However, it is important to emphasize that the maximum potential of the technology can only be realized by an educated handling of its limitations. Full article

(This article belongs to the Special Issue 10th Anniversary of Proteomes—Reviewing the Progress and Prospects of Proteomics)

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