Functional Proteomics 2020

A special issue of Proteomes (ISSN 2227-7382).

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 40901

Special Issue Editor


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Guest Editor
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
Interests: proteomics; metabolism; skeletal muscle proteomics; diabetes; obesity; diet and exercise

Special Issue Information

Dear Colleagues,

Mass spectrometry (MS)-based proteomics have revolutionized biomedical research over the last two decades. High-resolution MS-based proteomics allows for the investigation of protein dynamics by measuring multiple features such as expression, secretion, turnover rate, subcellular localization, interaction, and post-translational modifications (PTMs). During the last 10 years, MS-based proteomics has progressed tremendously, due to massive improvements in sample preparation workflows, liquid chromatography (LC) and MS instrumentation, as well as sophisticated algorithms for protein quantification. Today, proteomics technology enables analysis of near-complete proteomes of mammalian organs, and the quantification of thousands of PTM sites. Although large-scale proteomics studies have advanced our understanding of numerous diseases, these studies often lack subsequent biological analysis describing underlying molecular mechanisms. Functional proteomics is an emerging research field that attempts to exploit a wealth of proteomics data to explain the biological functions of proteins, with the ultimate aim of dissecting cellular mechanisms at the molecular level.

This Special issue of Proteomes welcomes submissions of original research or review articles aiming at deciphering biological functions with the use of proteomics tools. Contributions will deal with the dynamics of proteins in their native and modified forms, with the combination of several “omics” approaches in contrasted physiological situations, as well as with technical advances in the proteomic field.

Prof. Dr. Atul Shahaji Deshmukh
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Proteomes is an international peer-reviewed open access quarterly journal published by MDPI.

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Keywords

  • Omics data integration
  • PTMs and expression proteomics
  • Secretomics
  • Interaction proteomics
  • Organelle proteomics
  • Quantitative proteomics

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Published Papers (6 papers)

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Research

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16 pages, 3766 KiB  
Article
Insulin and 5-Aminoimidazole-4-Carboxamide Ribonucleotide (AICAR) Differentially Regulate the Skeletal Muscle Cell Secretome
by Alba Gonzalez-Franquesa, Lone Peijs, Daniel T. Cervone, Ceren Koçana, Juleen R. Zierath and Atul S. Deshmukh
Proteomes 2021, 9(3), 37; https://doi.org/10.3390/proteomes9030037 - 3 Aug 2021
Cited by 5 | Viewed by 6327
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Functional Proteomics 2020)
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19 pages, 3383 KiB  
Article
In-Depth Analysis of the Plasma Proteome in ME/CFS Exposes Disrupted Ephrin-Eph and Immune System Signaling
by Arnaud Germain, Susan M. Levine and Maureen R. Hanson
Proteomes 2021, 9(1), 6; https://doi.org/10.3390/proteomes9010006 - 29 Jan 2021
Cited by 11 | Viewed by 12411
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disease with worldwide prevalence and limited therapies exclusively aimed at treating symptoms. To gain insights into the molecular disruptions in ME/CFS, we utilized an aptamer-based technology that quantified 4790 unique human proteins, allowing us to [...] Read more.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disease with worldwide prevalence and limited therapies exclusively aimed at treating symptoms. To gain insights into the molecular disruptions in ME/CFS, we utilized an aptamer-based technology that quantified 4790 unique human proteins, allowing us to obtain the largest proteomics dataset yet available for this disease, detecting highly abundant proteins as well as rare proteins over a nine-log dynamic range. We report a pilot study of 20 ME/CFS patients and 20 controls, all females. Significant differences in the levels of 19 proteins between cohorts implicate pathways related to the extracellular matrix, the immune system and cell–cell communication. Outputs of pathway and cluster analyses robustly highlight the ephrin pathway, which is involved in cell–cell signaling and regulation of an expansive variety of biological processes, including axon guidance, angiogenesis, epithelial cell migration, and immune response. Receiver Operating Characteristic (ROC) curve analyses distinguish the plasma proteomes of ME/CFS patients from controls with a high degree of accuracy (Area Under the Curve (AUC) > 0.85), and even higher when using protein ratios (AUC up to 0.95), that include some protein pairs with established biological relevance. Our results illustrate the promise of plasma proteomics for diagnosing and deciphering the molecular basis of ME/CFS. Full article
(This article belongs to the Special Issue Functional Proteomics 2020)
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Review

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15 pages, 999 KiB  
Review
Comprehending the Proteomic Landscape of Ovarian Cancer: A Road to the Discovery of Disease Biomarkers
by Shuvolina Mukherjee, Karin Sundfeldt, Carl A. K. Borrebaeck and Magnus E. Jakobsson
Proteomes 2021, 9(2), 25; https://doi.org/10.3390/proteomes9020025 - 25 May 2021
Cited by 5 | Viewed by 4898
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, [...] Read more.
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. Full article
(This article belongs to the Special Issue Functional Proteomics 2020)
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12 pages, 27066 KiB  
Review
Current State of SLC and ABC Transporters in the Skin and Their Relation to Sweat Metabolites and Skin Diseases
by Marcus M. K. Nielsen, Eva Aryal, Elnaz Safari, Biljana Mojsoska, Håvard Jenssen and Bala Krishna Prabhala
Proteomes 2021, 9(2), 23; https://doi.org/10.3390/proteomes9020023 - 16 May 2021
Cited by 11 | Viewed by 6199
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Functional Proteomics 2020)
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17 pages, 3332 KiB  
Review
Combining Mass Spectrometry-Based Phosphoproteomics with a Network-Based Approach to Reveal FLT3-Dependent Mechanisms of Chemoresistance
by Giusj Monia Pugliese, Sara Latini, Giorgia Massacci, Livia Perfetto and Francesca Sacco
Proteomes 2021, 9(2), 19; https://doi.org/10.3390/proteomes9020019 - 27 Apr 2021
Cited by 3 | Viewed by 3693
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Functional Proteomics 2020)
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29 pages, 1869 KiB  
Review
Exosome-Derived Mediators as Potential Biomarkers for Cardiovascular Diseases: A Network Approach
by Liliana Moreira-Costa, António S. Barros, André P. Lourenço, Adelino F. Leite-Moreira, Rita Nogueira-Ferreira, Visith Thongboonkerd and Rui Vitorino
Proteomes 2021, 9(1), 8; https://doi.org/10.3390/proteomes9010008 - 1 Feb 2021
Cited by 23 | Viewed by 5832
Abstract
Cardiovascular diseases (CVDs) are widely recognized as the leading cause of mortality worldwide. Despite the advances in clinical management over the past decades, the underlying pathological mechanisms remain largely unknown. Exosomes have drawn the attention of researchers for their relevance in intercellular communication [...] Read more.
Cardiovascular diseases (CVDs) are widely recognized as the leading cause of mortality worldwide. Despite the advances in clinical management over the past decades, the underlying pathological mechanisms remain largely unknown. Exosomes have drawn the attention of researchers for their relevance in intercellular communication under both physiological and pathological conditions. These vesicles are suggested as complementary prospective biomarkers of CVDs; however, the role of exosomes in CVDs is still not fully elucidated. Here, we performed a literature search on exosomal biogenesis, characteristics, and functions, as well as the different available exosomal isolation techniques. Moreover, aiming to give new insights into the interaction between exosomes and CVDs, network analysis on the role of exosome-derived mediators in coronary artery disease (CAD) and heart failure (HF) was also performed to incorporate the different sources of information. The upregulated exosomal miRNAs miR-133a, miR-208a, miR-1, miR-499-5p, and miR-30a were described for the early diagnosis of acute myocardial infarction, while the exosome-derived miR-192, miR-194, miR-146a, and miR-92b-5p were considered as potential biomarkers for HF development. In CAD patients, upregulated exosomal proteins, including fibrinogen beta/gamma chain, inter-alpha-trypsin inhibitor heavy chain, and alpha-1 antichymotrypsin, were assessed as putative protein biomarkers. From downregulated proteins in CAD patients, albumin, clusterin, and vitamin D-binding protein were considered relevant to assess prognosis. The Vesiclepedia database included miR-133a of exosomal origin upregulated in patients with CAD and the exosomal miR-192, miR-194, and miR-146a upregulated in patients with HF. Additionally, Vesiclepedia included 5 upregulated and 13 downregulated exosomal proteins in patients in CAD. The non-included miRNAs and proteins have not yet been identified in exosomes and can be proposed for further research. This report highlights the need for further studies focusing on the identification and validation of miRNAs and proteins of exosomal origin as biomarkers of CAD and HF, which will enable, using exosomal biomarkers, the guiding of diagnosis/prognosis in CVDs. Full article
(This article belongs to the Special Issue Functional Proteomics 2020)
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