Journal Description
Proteomes
Proteomes
is an international, peer-reviewed, open access journal on all aspects of proteomics, published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, ESCI (Web of Science), PubMed, PMC, CAPlus / SciFinder, and many other databases.
- Journal Rank: CiteScore - Q2 (Clinical Biochemistry)
- Rapid Publication: manuscripts are peer-reviewed and a first decision provided to authors approximately 19.2 days after submission; acceptance to publication is undertaken in 3.6 days (median values for papers published in this journal in the first half of 2021).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Latest Articles
Proteomes Are of Proteoforms: Embracing the Complexity
Proteomes 2021, 9(3), 38; https://doi.org/10.3390/proteomes9030038 (registering DOI) - 31 Aug 2021
Abstract
Proteomes are complex—much more so than genomes or transcriptomes. Thus, simplifying their analysis does not simplify the issue. Proteomes are of proteoforms, not canonical proteins. While having a catalogue of amino acid sequences provides invaluable information, this is the Proteome-lite. To dissect biological
[...] Read more.
Proteomes are complex—much more so than genomes or transcriptomes. Thus, simplifying their analysis does not simplify the issue. Proteomes are of proteoforms, not canonical proteins. While having a catalogue of amino acid sequences provides invaluable information, this is the Proteome-lite. To dissect biological mechanisms and identify critical biomarkers/drug targets, we must assess the myriad of proteoforms that arise at any point before, after, and between translation and transcription (e.g., isoforms, splice variants, and post-translational modifications [PTM]), as well as newly defined species. There are numerous analytical methods currently used to address proteome depth and here we critically evaluate these in terms of the current ‘state-of-the-field’. We thus discuss both pros and cons of available approaches and where improvements or refinements are needed to quantitatively characterize proteomes. To enable a next-generation approach, we suggest that advances lie in transdisciplinarity via integration of current proteomic methods to yield a unified discipline that capitalizes on the strongest qualities of each. Such a necessary (if not revolutionary) shift cannot be accomplished by a continued primary focus on proteo-genomics/-transcriptomics. We must embrace the complexity. Yes, these are the hard questions, and this will not be easy…but where is the fun in easy?
Full article
(This article belongs to the Special Issue Feature Review Papers in Proteomes)
Open AccessArticle
Insulin and 5-Aminoimidazole-4-Carboxamide Ribonucleotide (AICAR) Differentially Regulate the Skeletal Muscle Cell Secretome
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Proteomes 2021, 9(3), 37; https://doi.org/10.3390/proteomes9030037 - 03 Aug 2021
Abstract
Skeletal muscle is a major contributor to whole-body glucose homeostasis and is an important endocrine organ. To date, few studies have undertaken the large-scale identification of skeletal muscle-derived secreted proteins (myokines), particularly in response to stimuli that activate pathways governing energy metabolism in
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Skeletal muscle is a major contributor to whole-body glucose homeostasis and is an important endocrine organ. To date, few studies have undertaken the large-scale identification of skeletal muscle-derived secreted proteins (myokines), particularly in response to stimuli that activate pathways governing energy metabolism in health and disease. Whereas the AMP-activated protein kinase (AMPK) and insulin-signaling pathways have received notable attention for their ability to independently regulate skeletal muscle substrate metabolism, little work has examined their ability to re-pattern the secretome. The present study coupled the use of high-resolution MS-based proteomics and bioinformatics analysis of conditioned media derived from 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR—an AMPK activator)- and insulin-treated differentiated C2C12 myotubes. We quantified 858 secreted proteins, including cytokines and growth factors such as fibroblast growth factor-21 (Fgf21). We identified 377 and 118 proteins that were significantly altered by insulin and AICAR treatment, respectively. Notably, the family of insulin growth factor binding-proteins (Igfbp) was differentially regulated by each treatment. Insulin- but not AICAR-induced conditioned media increased the mitochondrial respiratory capacity of myotubes, potentially via secreted factors. These findings may serve as an important resource to elucidate secondary metabolic effects of insulin and AICAR stimulation in skeletal muscle.
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(This article belongs to the Special Issue Functional Proteomics 2020)
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Open AccessArticle
CSF Proteomic Alzheimer’s Disease-Predictive Subtypes in Cognitively Intact Amyloid Negative Individuals
Proteomes 2021, 9(3), 36; https://doi.org/10.3390/proteomes9030036 - 02 Aug 2021
Abstract
We recently discovered three distinct pathophysiological subtypes in Alzheimer’s disease (AD) using cerebrospinal fluid (CSF) proteomics: one with neuronal hyperplasticity, a second with innate immune system activation, and a third subtype with blood–brain barrier dysfunction. It remains unclear whether AD proteomic subtype profiles
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We recently discovered three distinct pathophysiological subtypes in Alzheimer’s disease (AD) using cerebrospinal fluid (CSF) proteomics: one with neuronal hyperplasticity, a second with innate immune system activation, and a third subtype with blood–brain barrier dysfunction. It remains unclear whether AD proteomic subtype profiles are a consequence of amyloid aggregation, or might exist upstream from aggregated amyloid. We studied this question in 127 older individuals with intact cognition and normal AD biomarkers in two independent cohorts (EMIF-AD MBD and ADNI). We clustered 705 proteins measured in CSF that were previously related to AD. We identified in these cognitively intact individuals without AD pathology three subtypes: two subtypes were seen in both cohorts (n = 49 with neuronal hyperplasticity and n = 44 with blood–brain barrier dysfunction), and one only in ADNI (n = 12 with innate immune activation). The proteins specific for these subtypes strongly overlapped with AD subtype protein profiles (overlap coefficients 92%–71%). Longitudinal p181-tau and amyloid β 1–42 (Aβ42) CSF analysis showed that in the hyperplasticity subtype p181-tau increased (β = 2.6 pg/mL per year, p = 0.01) and Aβ42 decreased over time (β = −4.4 pg/mL per year, p = 0.03), in the innate immune activation subtype p181-tau increased (β = 3.1 pg/mL per year, p = 0.01) while in the blood–brain barrier dysfunction subtype Aβ42 decreased (β = −3.7 pg/mL per year, p = 0.009). These findings suggest that AD proteomic subtypes might already manifest in cognitively normal individuals and may predispose for AD before amyloid has reached abnormal levels.
Full article
(This article belongs to the Special Issue Proteomics in Neurodegenerative Diseases)
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Open AccessArticle
Impact of Exposure to Chronic Light–Dark Phase Shifting Circadian Rhythm Disruption on Muscle Proteome in Periparturient Dairy Cows
Proteomes 2021, 9(3), 35; https://doi.org/10.3390/proteomes9030035 - 29 Jul 2021
Abstract
Muscle tissue serves as a key nutrient reservoir that dairy cows utilize to meet energy and amino acid requirements for fetal growth and milk production. Circadian clocks act as homeostatic regulators so that organisms can anticipate regular environmental changes. The objective of this
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Muscle tissue serves as a key nutrient reservoir that dairy cows utilize to meet energy and amino acid requirements for fetal growth and milk production. Circadian clocks act as homeostatic regulators so that organisms can anticipate regular environmental changes. The objective of this study was to use liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine how chronic circadian disruption in late gestation affected the muscle tissue proteome. At five weeks before expected calving (BEC), multiparous Holstein cows were assigned to either a control (CON, n = 8) or a 6 h forward phase shift (PS, n = 8) of the light–dark cycle every 3 days. At calving, all animals were exposed to CON light–dark cycles. Muscle biopsies were collected from longissimus dorsi muscles at 21 days BEC and at 21 days postpartum (PP). At p < 0.1, 116 and 121 proteins were differentially abundant between PS and CON at 21 days BEC and 21 days PP, respectively. These proteins regulate beta oxidation and glycolysis. Between pregnancy and lactation, 134 and 145 proteins were differentially abundant in CON and PS cows, respectively (p < 0.1). At both timepoints, PS cows exhibited an oxidative stress signature. Thus, dairy cattle management strategies that minimize circadian disruptions may ensure optimal health and production performance.
Full article
(This article belongs to the Special Issue Mass Spectrometry-Based Quantitative Proteomics)
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Open AccessReview
Evaluation of the Sensitivity of Proteomics Methods Using the Absolute Copy Number of Proteins in a Single Cell as a Metric
Proteomes 2021, 9(3), 34; https://doi.org/10.3390/proteomes9030034 - 20 Jul 2021
Abstract
Proteomic technology has improved at a staggering pace in recent years, with even practitioners challenged to keep up with new methods and hardware. The most common metric used for method performance is the number of peptides and proteins identified. While this metric may
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Proteomic technology has improved at a staggering pace in recent years, with even practitioners challenged to keep up with new methods and hardware. The most common metric used for method performance is the number of peptides and proteins identified. While this metric may be helpful for proteomics researchers shopping for new hardware, this is often not the most biologically relevant metric. Biologists often utilize proteomics in the search for protein regulators that are of a lower relative copy number in the cell. In this review, I re-evaluate untargeted proteomics data using a simple graphical representation of the absolute copy number of proteins present in a single cancer cell as a metric. By comparing single-shot proteomics data to the coverage of the most in-depth proteomic analysis of that cell line acquired to date, we can obtain a rapid metric of method performance. Using a simple copy number metric allows visualization of how proteomics has developed in both sensitivity and overall dynamic range when using both relatively long and short acquisition times. To enable reanalysis beyond what is presented here, two available web applications have been developed for single- and multi-experiment comparisons with reference protein copy number data for multiple cell lines and organisms.
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(This article belongs to the Special Issue Feature Review Papers in Proteomes)
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Open AccessArticle
Downregulation of Salivary Proteins, Protective against Dental Caries, in Type 1 Diabetes
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Proteomes 2021, 9(3), 33; https://doi.org/10.3390/proteomes9030033 - 19 Jul 2021
Abstract
Saliva, an essential oral secretion involved in protecting the oral cavity’s hard and soft tissues, is readily available and straightforward to collect. Recent studies have analyzed the salivary proteome in children and adolescents with extensive carious lesions to identify diagnostic and prognostic biomarkers.
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Saliva, an essential oral secretion involved in protecting the oral cavity’s hard and soft tissues, is readily available and straightforward to collect. Recent studies have analyzed the salivary proteome in children and adolescents with extensive carious lesions to identify diagnostic and prognostic biomarkers. The current study aimed to investigate saliva’s diagnostic ability through proteomics to detect the potential differential expression of proteins specific for the occurrence of carious lesions. For this study, we performed bioinformatics and functional analysis of proteomic datasets, previously examined by our group, from samples of adolescents with regulated and unregulated type 1 diabetes, as they compare with healthy controls. Among the differentially expressed proteins relevant to caries pathology, alpha-amylase 2B, beta-defensin 4A, BPI fold containing family B member 2, protein S100-A7, mucin 5B, statherin, salivary proline-rich protein 2, and interleukin 36 gamma were significantly downregulated in poorly-controlled patients compared to healthy subjects. In addition, significant biological pathways (defense response to the bacterium, beta-defensin activity, proline-rich protein activity, oxygen binding, calcium binding, and glycosylation) were deregulated in this comparison, highlighting specific molecular characteristics in the cariogenic process. This analysis contributes to a better understanding of the mechanisms involved in caries vulnerability in adolescents with unregulated diabetes.
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(This article belongs to the Special Issue Proteomics of Body Fluids: Principles, Methods, and Applications)
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Open AccessArticle
A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease
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Proteomes 2021, 9(3), 32; https://doi.org/10.3390/proteomes9030032 - 13 Jul 2021
Abstract
Non-invasive urinary peptide biomarkers are able to detect and predict chronic kidney disease (CKD). Moreover, specific urinary peptides enable discrimination of different CKD etiologies and offer an interesting alternative to invasive kidney biopsy, which cannot always be performed. The aim of this study
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Non-invasive urinary peptide biomarkers are able to detect and predict chronic kidney disease (CKD). Moreover, specific urinary peptides enable discrimination of different CKD etiologies and offer an interesting alternative to invasive kidney biopsy, which cannot always be performed. The aim of this study was to define a urinary peptide classifier using mass spectrometry technology to predict the degree of renal interstitial fibrosis and tubular atrophy (IFTA) in CKD patients. The urinary peptide profiles of 435 patients enrolled in this study were analyzed using capillary electrophoresis coupled with mass spectrometry (CE-MS). Urine samples were collected on the day of the diagnostic kidney biopsy. The proteomics data were divided into a training (n = 200) and a test (n = 235) cohort. The fibrosis group was defined as IFTA ≥ 15% and no fibrosis as IFTA < 10%. Statistical comparison of the mass spectrometry data enabled identification of 29 urinary peptides with differential occurrence in samples with and without fibrosis. Several collagen fragments and peptide fragments of fetuin-A and others were combined into a peptidomic classifier. The classifier separated fibrosis from non-fibrosis patients in an independent test set (n = 186) with area under the curve (AUC) of 0.84 (95% CI: 0.779 to 0.889). A significant correlation of IFTA and FPP_BH29 scores could be observed Rho = 0.5, p < 0.0001. We identified a peptidomic classifier for renal fibrosis containing 29 peptide fragments corresponding to 13 different proteins. Urinary proteomics analysis can serve as a non-invasive tool to evaluate the degree of renal fibrosis, in contrast to kidney biopsy, which allows repeated measurements during the disease course.
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(This article belongs to the Special Issue Mass Spectrometry-Based Quantitative Proteomics)
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Open AccessReview
Applied Proteomics in ‘One Health’
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Proteomes 2021, 9(3), 31; https://doi.org/10.3390/proteomes9030031 - 30 Jun 2021
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‘One Health’ summarises the idea that human health and animal health are interdependent and bound to the health of ecosystems. The purpose of proteomics methodologies and studies is to determine proteins present in samples of interest and to quantify changes in protein expression
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‘One Health’ summarises the idea that human health and animal health are interdependent and bound to the health of ecosystems. The purpose of proteomics methodologies and studies is to determine proteins present in samples of interest and to quantify changes in protein expression during pathological conditions. The objectives of this paper are to review the application of proteomics technologies within the One Health concept and to appraise their role in the elucidation of diseases and situations relevant to One Health. The paper develops in three sections. Proteomics Applications in Zoonotic Infections part discusses proteomics applications in zoonotic infections and explores the use of proteomics for studying pathogenetic pathways, transmission dynamics, diagnostic biomarkers and novel vaccines in prion, viral, bacterial, protozoan and metazoan zoonotic infections. Proteomics Applications in Antibiotic Resistance part discusses proteomics applications in mechanisms of resistance development and discovery of novel treatments for antibiotic resistance. Proteomics Applications in Food Safety part discusses the detection of allergens, exposure of adulteration, identification of pathogens and toxins, study of product traits and characterisation of proteins in food safety. Sensitive analysis of proteins, including low-abundant ones in complex biological samples, will be achieved in the future, thus enabling implementation of targeted proteomics in clinical settings, shedding light on biomarker research and promoting the One Health concept.
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Open AccessArticle
H2B Type 1-K Accumulates in Senescent Fibroblasts with Persistent DNA Damage along with Methylated and Phosphorylated Forms of HMGA1
Proteomes 2021, 9(2), 30; https://doi.org/10.3390/proteomes9020030 - 21 Jun 2021
Abstract
Cellular senescence is a state of terminal proliferative arrest that plays key roles in aging by preventing stem cell renewal and by inducing the expression of a series of inflammatory factors including many secreted proteins with paracrine effects. The in vivo identification of
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Cellular senescence is a state of terminal proliferative arrest that plays key roles in aging by preventing stem cell renewal and by inducing the expression of a series of inflammatory factors including many secreted proteins with paracrine effects. The in vivo identification of senescent cells is difficult due to the absence of universal biomarkers. Chromatin modifications are key aspects of the senescence transition and may provide novel biomarkers. We used a combined protein profiling and bottom-up mass spectrometry approach to characterize the isoforms and post-translational modifications of chromatin proteins over time in post-mitotic human fibroblasts in vitro. We show that the H2B type 1-K variant is specifically enriched in deep senescent cells with persistent DNA damage. This accumulation was not observed in quiescent cells or in cells induced into senescence without DNA damage by expression of the RAF kinase. Similarly, HMGA1a di-methylated and HMGA1b tri-phosphorylated forms accumulated exclusively in the chromatin of cells in deep senescent conditions with persistent DNA damage. H2B type 1-K and modified HMGA1 may thus represent novel biomarkers of senescent cells containing persistent DNA damage.
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(This article belongs to the Special Issue Latest Discoveries and Proteomics-Based Methods in Histone Biology)
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Open AccessArticle
Mining Proteome Research Reports: A Bird’s Eye View
Proteomes 2021, 9(2), 29; https://doi.org/10.3390/proteomes9020029 - 10 Jun 2021
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The complexity of data has burgeoned to such an extent that scientists of every realm are encountering the incessant challenge of data management. Modern-day analytical approaches with the help of free source tools and programming languages have facilitated access to the context of
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The complexity of data has burgeoned to such an extent that scientists of every realm are encountering the incessant challenge of data management. Modern-day analytical approaches with the help of free source tools and programming languages have facilitated access to the context of the various domains as well as specific works reported. Here, with this article, an attempt has been made to provide a systematic analysis of all the available reports at PubMed on Proteome using text mining. The work is comprised of scientometrics as well as information extraction to provide the publication trends as well as frequent keywords, bioconcepts and most importantly gene–gene co-occurrence network. Out of 33,028 PMIDs collected initially, the segregation of 24,350 articles under 28 Medical Subject Headings (MeSH) was analyzed and plotted. Keyword link network and density visualizations were provided for the top 1000 frequent Mesh keywords. PubTator was used, and 322,026 bioconcepts were able to extracted under 10 classes (such as Gene, Disease, CellLine, etc.). Co-occurrence networks were constructed for PMID-bioconcept as well as bioconcept–bioconcept associations. Further, for creation of subnetwork with respect to gene–gene co-occurrence, a total of 11,100 unique genes participated with mTOR and AKT showing the highest (64) number of connections. The gene p53 was the most popular one in the network in accordance with both the degree and weighted degree centrality, which were 425 and 1414, respectively. The present piece of study is an amalgam of bibliometrics and scientific data mining methods looking deeper into the whole scale analysis of available literature on proteome.
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Open AccessArticle
Advanced Fiber Type-Specific Protein Profiles Derived from Adult Murine Skeletal Muscle
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Proteomes 2021, 9(2), 28; https://doi.org/10.3390/proteomes9020028 - 08 Jun 2021
Abstract
Skeletal muscle is a heterogeneous tissue consisting of blood vessels, connective tissue, and muscle fibers. The last are highly adaptive and can change their molecular composition depending on external and internal factors, such as exercise, age, and disease. Thus, examination of the skeletal
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Skeletal muscle is a heterogeneous tissue consisting of blood vessels, connective tissue, and muscle fibers. The last are highly adaptive and can change their molecular composition depending on external and internal factors, such as exercise, age, and disease. Thus, examination of the skeletal muscles at the fiber type level is essential to detect potential alterations. Therefore, we established a protocol in which myosin heavy chain isoform immunolabeled muscle fibers were laser microdissected and separately investigated by mass spectrometry to develop advanced proteomic profiles of all murine skeletal muscle fiber types. All data are available via ProteomeXchange with the identifier PXD025359. Our in-depth mass spectrometric analysis revealed unique fiber type protein profiles, confirming fiber type-specific metabolic properties and revealing a more versatile function of type IIx fibers. Furthermore, we found that multiple myopathy-associated proteins were enriched in type I and IIa fibers. To further optimize the assignment of fiber types based on the protein profile, we developed a hypothesis-free machine-learning approach, identified a discriminative peptide panel, and confirmed our panel using a public data set.
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(This article belongs to the Special Issue Striated Muscle Proteomics II)
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Phosphorylation-Dependent Interactome of Ryanodine Receptor Type 2 in the Heart
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Proteomes 2021, 9(2), 27; https://doi.org/10.3390/proteomes9020027 - 07 Jun 2021
Abstract
Hyperphosphorylation of the calcium release channel/ryanodine receptor type 2 (RyR2) at serine 2814 (S2814) is associated with multiple cardiac diseases including atrial fibrillation and heart failure. Despite recent advances, the molecular mechanisms driving pathological changes associated with RyR2 S2814 phosphorylation are still not
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Hyperphosphorylation of the calcium release channel/ryanodine receptor type 2 (RyR2) at serine 2814 (S2814) is associated with multiple cardiac diseases including atrial fibrillation and heart failure. Despite recent advances, the molecular mechanisms driving pathological changes associated with RyR2 S2814 phosphorylation are still not well understood. Methods: Using affinity-purification coupled to mass spectrometry (AP-MS), we investigated the RyR2 interactome in ventricles from wild-type (WT) mice and two S2814 knock-in mutants: the unphosphorylated alanine mutant (S2814A) and hyperphosphorylated mimic aspartic acid mutant (S2814D). Western blots were used for validation. Results: In WT mouse ventricular lysates, we identified 22 proteins which were enriched with RyR2 pull-down relative to both IgG control and no antibody (beads-only) pull-downs. Parallel AP-MS using WT, S2814A, and S2814D mouse ventricles identified 72 proteins, with 20 being high confidence RyR2 interactors. Of these, 14 had an increase in their binding to RyR2 S2814A but a decrease in their binding to RyR2 S2814D. We independently validated three protein hits, Idh3b, Aifm1, and Cpt1b, as RyR2 interactors by western blots and showed that Aifm1 and Idh3b had significantly decreased binding to RyR2 S2814D compared to WT and S2814A, consistent with MS findings. Conclusion: By applying state-of-the-art proteomic approaches, we discovered a number of novel RyR2 interactors in the mouse heart. In addition, we found and defined specific alterations in the RyR2 interactome that were dependent on the phosphorylation status of RyR2 at S2814. These findings yield mechanistic insights into RyR2 regulation which may guide future drug designs.
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(This article belongs to the Special Issue Striated Muscle Proteomics II)
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A Systematic Evaluation of Semispecific Peptide Search Parameter Enables Identification of Previously Undescribed N-Terminal Peptides and Conserved Proteolytic Processing in Cancer Cell Lines
Proteomes 2021, 9(2), 26; https://doi.org/10.3390/proteomes9020026 - 25 May 2021
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Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the most commonly used technique in explorative proteomic research. A variety of open-source tools for peptide-spectrum matching have become available. Most analyses of explorative MS data are performed using conventional settings, such as fully specific enzymatic
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Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the most commonly used technique in explorative proteomic research. A variety of open-source tools for peptide-spectrum matching have become available. Most analyses of explorative MS data are performed using conventional settings, such as fully specific enzymatic constraints. Here we evaluated the impact of the fragment mass tolerance in combination with the enzymatic constraints on the performance of three search engines. Three open-source search engines (Myrimatch, X! Tandem, and MSGF+) were evaluated concerning the suitability in semi- and unspecific searches as well as the importance of accurate fragment mass spectra in non-specific peptide searches. We then performed a semispecific reanalysis of the published NCI-60 deep proteome data applying the most suited parameters. Semi- and unspecific LC-MS/MS data analyses particularly benefit from accurate fragment mass spectra while this effect is less pronounced for conventional, fully specific peptide-spectrum matching. Search speed differed notably between the three search engines for semi- and non-specific peptide-spectrum matching. Semispecific reanalysis of NCI-60 proteome data revealed hundreds of previously undescribed N-terminal peptides, including cases of proteolytic processing or likely alternative translation start sites, some of which were ubiquitously present in all cell lines of the reanalyzed panel. Highly accurate MS2 fragment data in combination with modern open-source search algorithms enable the confident identification of semispecific peptides from large proteomic datasets. The identification of previously undescribed N-terminal peptides in published studies highlights the potential of future reanalysis and data mining in proteomic datasets.
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Open AccessReview
Comprehending the Proteomic Landscape of Ovarian Cancer: A Road to the Discovery of Disease Biomarkers
Proteomes 2021, 9(2), 25; https://doi.org/10.3390/proteomes9020025 - 25 May 2021
Abstract
Despite recent technological advancements allowing the characterization of cancers at a molecular level along with biomarkers for cancer diagnosis, the management of ovarian cancers (OC) remains challenging. Proteins assume functions encoded by the genome and the complete set of proteins, termed the proteome,
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Despite recent technological advancements allowing the characterization of cancers at a molecular level along with biomarkers for cancer diagnosis, the management of ovarian cancers (OC) remains challenging. Proteins assume functions encoded by the genome and the complete set of proteins, termed the proteome, reflects the health state. Comprehending the circulatory proteomic profiles for OC subtypes, therefore, has the potential to reveal biomarkers with clinical utility concerning early diagnosis or to predict response to specific therapies. Furthermore, characterization of the proteomic landscape of tumor-derived tissue, cell lines, and PDX models has led to the molecular stratification of patient groups, with implications for personalized therapy and management of drug resistance. Here, we review single and multiple marker panels that have been identified through proteomic investigations of patient sera, effusions, and other biospecimens. We discuss their clinical utility and implementation into clinical practice.
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(This article belongs to the Special Issue Functional Proteomics 2020)
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A Novel Method for Creating a Synthetic L-DOPA Proteome and In Vitro Evidence of Incorporation
Proteomes 2021, 9(2), 24; https://doi.org/10.3390/proteomes9020024 - 24 May 2021
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Proteinopathies are protein misfolding diseases that have an underlying factor that affects the conformation of proteoforms. A factor hypothesised to play a role in these diseases is the incorporation of non-protein amino acids into proteins, with a key example being the therapeutic drug
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Proteinopathies are protein misfolding diseases that have an underlying factor that affects the conformation of proteoforms. A factor hypothesised to play a role in these diseases is the incorporation of non-protein amino acids into proteins, with a key example being the therapeutic drug levodopa. The presence of levodopa as a protein constituent has been explored in several studies, but it has not been examined in a global proteomic manner. This paper provides a proof-of-concept method for enzymatically creating levodopa-containing proteins using the enzyme tyrosinase and provides spectral evidence of in vitro incorporation in addition to the induction of the unfolded protein response due to levodopa.
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Open AccessReview
Current State of SLC and ABC Transporters in the Skin and Their Relation to Sweat Metabolites and Skin Diseases
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Proteomes 2021, 9(2), 23; https://doi.org/10.3390/proteomes9020023 - 16 May 2021
Abstract
With a relatively large surface area (2 m2) and 15% of total body mass, the skin forms the largest organ of the human body. The main functions of the skin include regulation of body temperature by insulation or sweating, regulation of
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With a relatively large surface area (2 m2) and 15% of total body mass, the skin forms the largest organ of the human body. The main functions of the skin include regulation of body temperature by insulation or sweating, regulation of the nervous system, regulation of water content, and protection against external injury. To perform these critical functions, the skin encodes genes for transporters responsible for the cellular trafficking of essential nutrients and metabolites to maintain cellular hemostasis. However, the knowledge on the expression, regulation, and function of these transporters is very limited and needs more work to elucidate how these transporters play a role both in disease progression and in healing. Furthermore, SLC and ABC transporters are understudied, and even less studied in skin. There are sparse reports on relation between transporters in skin and sweat metabolites. This mini review focuses on the current state of SLC and ABC transporters in the skin and their relation to sweat metabolites and skin diseases.
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(This article belongs to the Special Issue Functional Proteomics 2020)
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Western Diet Induced Remodelling of the Tongue Proteome
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Proteomes 2021, 9(2), 22; https://doi.org/10.3390/proteomes9020022 - 12 May 2021
Abstract
The tongue is a heavily innervated and vascularized striated muscle that plays an important role in vocalization, swallowing and digestion. The surface of the tongue is lined with papillae which contain gustatory cells expressing various taste receptors. There is growing evidence to suggest
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The tongue is a heavily innervated and vascularized striated muscle that plays an important role in vocalization, swallowing and digestion. The surface of the tongue is lined with papillae which contain gustatory cells expressing various taste receptors. There is growing evidence to suggest that our perceptions of taste and food preference are remodelled following chronic consumption of Western diets rich in carbohydrate and fats. Our sensitivity to taste and also to metabolising Western diets may be a key factor in the rising prevalence of obesity; however, a systems-wide analysis of the tongue is lacking. Here, we defined the proteomic landscape of the mouse tongue and quantified changes following chronic consumption of a chow or Western diet enriched in lipid, fructose and cholesterol for 7 months. We observed a dramatic remodelling of the tongue proteome including proteins that regulate fatty acid and mitochondrial metabolism. Furthermore, the expressions of several receptors, metabolic enzymes and hormones were differentially regulated, and are likely to provide novel therapeutic targets to alter taste perception and food preference to combat obesity.
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(This article belongs to the Special Issue Striated Muscle Proteomics II)
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Protamine Characterization by Top-Down Proteomics: Boosting Proteoform Identification with DBSCAN
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Proteomes 2021, 9(2), 21; https://doi.org/10.3390/proteomes9020021 - 30 Apr 2021
Abstract
Protamines replace histones as the main nuclear protein in the sperm cells of many species and play a crucial role in compacting the paternal genome. Human spermatozoa contain protamine 1 (P1) and the family of protamine 2 (P2) proteins. Alterations in protamine PTMs
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Protamines replace histones as the main nuclear protein in the sperm cells of many species and play a crucial role in compacting the paternal genome. Human spermatozoa contain protamine 1 (P1) and the family of protamine 2 (P2) proteins. Alterations in protamine PTMs or the P1/P2 ratio may be associated with male infertility. Top-down proteomics enables large-scale analysis of intact proteoforms derived from alternative splicing, missense or nonsense genetic variants or PTMs. In contrast to current gold standard techniques, top-down proteomics permits a more in-depth analysis of protamine PTMs and proteoforms, thereby opening up new perspectives to unravel their impact on male fertility. We report on the analysis of two normozoospermic semen samples by top-down proteomics. We discuss the difficulties encountered with the data analysis and propose solutions as this step is one of the current bottlenecks in top-down proteomics with the bioinformatics tools currently available. Our strategy for the data analysis combines two software packages, ProSight PD (PS) and TopPIC suite (TP), with a clustering algorithm to decipher protamine proteoforms. We identified up to 32 protamine proteoforms at different levels of characterization. This in-depth analysis of the protamine proteoform landscape of normozoospermic individuals represents the first step towards the future study of sperm pathological conditions opening up the potential personalized diagnosis of male infertility.
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(This article belongs to the Special Issue Latest Discoveries and Proteomics-Based Methods in Histone Biology)
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Open AccessArticle
Macrophage Proteome Analysis at Different Stages of Mycobacterium avium Subspecies paratuberculosis Infection Reveals a Mechanism of Pathogen Dissemination
Proteomes 2021, 9(2), 20; https://doi.org/10.3390/proteomes9020020 - 30 Apr 2021
Cited by 1
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Johne’s disease is a chronic and usually fatal enteric infection of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP) and is responsible for hundreds of millions of dollars in losses for the agricultural industry. Natural infection typically begins with bacterial uptake and translocation
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Johne’s disease is a chronic and usually fatal enteric infection of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP) and is responsible for hundreds of millions of dollars in losses for the agricultural industry. Natural infection typically begins with bacterial uptake and translocation through the epithelium of the small intestine, followed by ingestion by tissue macrophages and dissemination via the lymphatic or blood system throughout the body. To gain insights into the host responses and adaptation of MAP within phagocytic cells, we utilized the previously developed cell culture passage model, and mass spectrometric-based quantitative proteomic approach. Using the cell culture system, which mimics an in vivo interaction of MAP with intestinal epithelium and tissue macrophages, bacteria were passed through the bovine epithelial cells and, subsequently, used for macrophage infection (termed indirect infection), while uninfected cells and macrophage infection initiated with the culture grown bacteria (termed direct infection) served as controls. Approximately 3900 proteins were identified across all studied groups. The comparison within the subset of proteins that showed synthesis for more than two-fold in the direct infection over the uninfected control revealed an enrichment for the pro-inflammatory pathways such as the NF-κB and cytokine/chemokine signaling, positive regulation of defense response, cell activation involved in the immune response and adaptive immune system. While these responses were absent in the indirect infection, cellular pathways such as cell cycle, healing, regulation of cell adhesion, ensemble of core extracellular matrix proteins, cell surface integrins and proteins mediating the integrin signaling were remarkably high within the indirect infection. In addition to global analysis of the macrophage proteome, we further validated the proteomics data and confirmed that MAP passage through epithelial cells modulates the expression and signaling of integrins in phagocytes. In this study, we demonstrate that predominant expression of integrins in the indirectly infected macrophages allows phagocytic cells to initiate stronger binding and efficient translocation through the endothelial cells, suggesting the important role of integrins in the spread of MAP infection.
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Combining Mass Spectrometry-Based Phosphoproteomics with a Network-Based Approach to Reveal FLT3-Dependent Mechanisms of Chemoresistance
Proteomes 2021, 9(2), 19; https://doi.org/10.3390/proteomes9020019 - 27 Apr 2021
Abstract
FLT3 mutations are the most frequently identified genetic alterations in acute myeloid leukemia (AML) and are associated with poor clinical outcome, relapse and chemotherapeutic resistance. Elucidating the molecular mechanisms underlying FLT3-dependent pathogenesis and drug resistance is a crucial goal of biomedical research. Given
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FLT3 mutations are the most frequently identified genetic alterations in acute myeloid leukemia (AML) and are associated with poor clinical outcome, relapse and chemotherapeutic resistance. Elucidating the molecular mechanisms underlying FLT3-dependent pathogenesis and drug resistance is a crucial goal of biomedical research. Given the complexity and intricacy of protein signaling networks, deciphering the molecular basis of FLT3-driven drug resistance requires a systems approach. Here we discuss how the recent advances in mass spectrometry (MS)-based (phospho) proteomics and multiparametric analysis accompanied by emerging computational approaches offer a platform to obtain and systematically analyze cell-specific signaling networks and to identify new potential therapeutic targets.
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(This article belongs to the Special Issue Functional Proteomics 2020)
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