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Deployment of Proteomics Approaches in Biomedical Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 8770

Special Issue Editors

Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), 31008 Pamplona, Spain
Interests: proteomics; cell signaling; systems biology; biomarkers
Special Issues, Collections and Topics in MDPI journals
Navarrabiomed-Biomedical Research Centre, 31008 Pamplona, Spain
Interests: proteomics; mass-spectrometry; neuroscience; cardiology; oncology

Special Issue Information

Dear Colleagues,

Next-generation proteomics has allowed the implementation of biomedical proteome research to uncover disease-affected protein expression profiles, as well as the determination of protein localization, protein interactomes, post-translational modifications and protein dysfunction in human diseases. Many pillars in personalized medicine, such as diagnostic improvements, drug screening, systems biology or bioinformatics, require the generation of quantitatively consistent proteomics data from translational animal models to human biospecimens.

The purpose of this Special Issue is to highlight the progress of proteomic methodologies in biomedical research, as well as in the implementation phases of personalized medicine. This openaccess Special Issue will bring together original research and review articles, especially in the fields of i) sex-/gender-specific pathophysiology, ii) the discovery/validation of biomarker candidates, iii) proteotype characterizations of cellular and animal models, or iv) the proteostatic modulation and mechanisms of action of pharmaceutical drugs. Technological/analytical developments in biomedical proteomics are also welcome.

Dr. Enrique Santamaría
Dr. Joaquín Fernández-Irigoyen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mass-spectrometry-based quantitative proteomics
  • protein interactomes
  • bioinformatics
  • post-translational modifications
  • biomarker detection
  • patient stratification
  • network biology
  • proteostasis
  • multi-omics data integration

Published Papers (7 papers)

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Editorial

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4 pages, 197 KiB  
Editorial
Special Issue “Deployment of Proteomics Approaches in Biomedical Research”
by Joaquín Fernández-Irigoyen and Enrique Santamaría
Int. J. Mol. Sci. 2024, 25(3), 1717; https://doi.org/10.3390/ijms25031717 - 31 Jan 2024
Viewed by 609
Abstract
Many angles of personalized medicine, such as diagnostic improvements, systems biology [...] Full article
(This article belongs to the Special Issue Deployment of Proteomics Approaches in Biomedical Research)

Research

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15 pages, 1920 KiB  
Article
Autoantibody Profiling and Anti-Kinesin Reactivity in ANCA-Associated Vasculitis
by Federica Mescia, Shaghayegh Bayati, Elisabeth Brouwer, Peter Heeringa, Erik J. M. Toonen, Marijke Beenes, Miriam J. Ball, Andrew J. Rees, Renate Kain, Paul A. Lyons, Peter Nilsson and Elisa Pin
Int. J. Mol. Sci. 2023, 24(20), 15341; https://doi.org/10.3390/ijms242015341 - 19 Oct 2023
Cited by 1 | Viewed by 778
Abstract
ANCA-associated vasculitides (AAV) are rare autoimmune diseases causing inflammation and damage to small blood vessels. New autoantibody biomarkers are needed to improve the diagnosis and treatment of AAV patients. In this study, we aimed to profile the autoantibody repertoire of AAV patients using [...] Read more.
ANCA-associated vasculitides (AAV) are rare autoimmune diseases causing inflammation and damage to small blood vessels. New autoantibody biomarkers are needed to improve the diagnosis and treatment of AAV patients. In this study, we aimed to profile the autoantibody repertoire of AAV patients using in-house developed antigen arrays to identify previously unreported antibodies linked to the disease per se, clinical subgroups, or clinical activity. A total of 1743 protein fragments representing 1561 unique proteins were screened in 229 serum samples collected from 137 AAV patients at presentation, remission, and relapse. Additionally, serum samples from healthy individuals and patients with other type of vasculitis and autoimmune-inflammatory conditions were included to evaluate the specificity of the autoantibodies identified in AAV. Autoreactivity against members of the kinesin protein family were identified in AAV patients, healthy volunteers, and disease controls. Anti-KIF4A antibodies were significantly more prevalent in AAV. We also observed possible associations between anti-kinesin antibodies and clinically relevant features within AAV patients. Further verification studies will be needed to confirm these findings. Full article
(This article belongs to the Special Issue Deployment of Proteomics Approaches in Biomedical Research)
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18 pages, 6880 KiB  
Article
Proteomic Profiling of Chemotherapy Responses in FOLFOX-Resistant Colorectal Cancer Cells
by Shing-Yau Tam, Md Zahirul Islam Khan, Ju-Yu Chen, Jerica Hiu-Yui Yip, Hong-Yiu Yan, Tsz-Yan Tam and Helen Ka-Wai Law
Int. J. Mol. Sci. 2023, 24(12), 9899; https://doi.org/10.3390/ijms24129899 - 08 Jun 2023
Cited by 2 | Viewed by 1311
Abstract
Chemoresistance mechanisms of colorectal cancer remain largely elusive. We aim to compare the difference of chemotherapy responses between FOLFOX-resistant and wild-type colorectal cancer cells by proteomic profiling to suggest novel treatment targets. FOLFOX-resistant colorectal cancer cells DLD1-R and HCT116-R were developed by chronic [...] Read more.
Chemoresistance mechanisms of colorectal cancer remain largely elusive. We aim to compare the difference of chemotherapy responses between FOLFOX-resistant and wild-type colorectal cancer cells by proteomic profiling to suggest novel treatment targets. FOLFOX-resistant colorectal cancer cells DLD1-R and HCT116-R were developed by chronic exposure to progressive FOLFOX doses. Proteomic profiling of FOLFOX-resistant and wild-type cells under FOLFOX exposure were conducted by mass-spectrometry-based protein-analysis technology. Verification of selected KEGG pathways was conducted by Western blot. DLD1-R had significantly higher FOLFOX-chemoresistance (10.81 times) than its wild-type counterpart. A total of 309 and 90 differentially expressed proteins were identified in DLD1-R and HCT116-R, respectively. In terms of gene ontology molecular function, RNA binding and cadherin binding ranked first for DLD1 and HCT116 groups, respectively. For gene set enrichment analysis, ribosome pathway and DNA replication were significantly up-regulated and down-regulated in DLD1-R, respectively. The most significantly up-regulated pathway in HCT116-R was regulation of the actin cytoskeleton. Up-regulations in the ribosome pathway (DLD1-R) and actin cytoskeleton (HCT116-R) were verified by Western blot. There were several significantly altered signaling pathways in FOLFOX-resistant colorectal cancer cells under FOLFOX with notable up-regulations in the ribosomal process and actin cytoskeleton. Full article
(This article belongs to the Special Issue Deployment of Proteomics Approaches in Biomedical Research)
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15 pages, 1563 KiB  
Article
Mix24X, a Lab-Assembled Reference to Evaluate Interpretation Procedures for Tandem Mass Spectrometry Proteotyping of Complex Samples
by Charlotte Mappa, Béatrice Alpha-Bazin, Olivier Pible and Jean Armengaud
Int. J. Mol. Sci. 2023, 24(10), 8634; https://doi.org/10.3390/ijms24108634 - 11 May 2023
Cited by 2 | Viewed by 1117
Abstract
Correct identification of the microorganisms present in a complex sample is a crucial issue. Proteotyping based on tandem mass spectrometry can help establish an inventory of organisms present in a sample. Evaluation of bioinformatics strategies and tools for mining the recorded datasets is [...] Read more.
Correct identification of the microorganisms present in a complex sample is a crucial issue. Proteotyping based on tandem mass spectrometry can help establish an inventory of organisms present in a sample. Evaluation of bioinformatics strategies and tools for mining the recorded datasets is essential to establish confidence in the results obtained and to improve these pipelines in terms of sensitivity and accuracy. Here, we propose several tandem mass spectrometry datasets recorded on an artificial reference consortium comprising 24 bacterial species. This assemblage of environmental and pathogenic bacteria covers 20 different genera and 5 bacterial phyla. The dataset comprises difficult cases, such as the Shigella flexneri species, which is closely related to Escherichia coli, and several highly sequenced clades. Different acquisition strategies simulate real-life scenarios: from rapid survey sampling to exhaustive analysis. We provide access to individual proteomes of each bacterium separately to provide a rational basis for evaluating the assignment strategy of MS/MS spectra when recorded from complex mixtures. This resource should provide an interesting common reference for developers who wish to compare their proteotyping tools and for those interested in evaluating protein assignment when dealing with complex samples, such as microbiomes. Full article
(This article belongs to the Special Issue Deployment of Proteomics Approaches in Biomedical Research)
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15 pages, 1784 KiB  
Article
Autoantibodies against PIP4K2B and AKT3 Are Associated with Skin and Lung Fibrosis in Patients with Systemic Sclerosis
by Marija Geroldinger-Simić, Shaghayegh Bayati, Emmie Pohjanen, Norbert Sepp, Peter Nilsson and Elisa Pin
Int. J. Mol. Sci. 2023, 24(6), 5629; https://doi.org/10.3390/ijms24065629 - 15 Mar 2023
Cited by 4 | Viewed by 1446
Abstract
Systemic sclerosis (SSc) is a rare autoimmune systemic disease that leads to decreased survival and quality of life due to fibrosis, inflammation, and vascular damage in the skin and/or vital organs. Early diagnosis is crucial for clinical benefit in SSc patients. Our study [...] Read more.
Systemic sclerosis (SSc) is a rare autoimmune systemic disease that leads to decreased survival and quality of life due to fibrosis, inflammation, and vascular damage in the skin and/or vital organs. Early diagnosis is crucial for clinical benefit in SSc patients. Our study aimed to identify autoantibodies in the plasma of SSc patients that are associated with fibrosis in SSc. Initially, we performed a proteome-wide screening on sample pools from SSc patients by untargeted autoantibody screening on a planar antigen array (including 42,000 antigens representing 18,000 unique proteins). The selection was complemented with proteins reported in the literature in the context of SSc. A targeted antigen bead array was then generated with protein fragments representing the selected proteins and used to screen 55 SSc plasma samples and 52 matched controls. We found eleven autoantibodies with a higher prevalence in SSc patients than in controls, eight of which bound to proteins associated with fibrosis. Combining these autoantibodies in a panel could lead to the subgrouping of SSc patients with fibrosis. Anti-Phosphatidylinositol-5-phosphate 4-kinase type 2 beta (PIP4K2B)- and anti-AKT Serine/Threonine Kinase 3 (AKT3)-antibodies should be further explored to confirm their association with skin and lung fibrosis in SSc patients. Full article
(This article belongs to the Special Issue Deployment of Proteomics Approaches in Biomedical Research)
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Review

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13 pages, 2110 KiB  
Review
The Altered Functions of Shelterin Components in ALT Cells
by Yanduo Zhang, Kailong Hou, Jinkai Tong, Haonan Zhang, Mengjie Xiong, Jing Liu and Shuting Jia
Int. J. Mol. Sci. 2023, 24(23), 16830; https://doi.org/10.3390/ijms242316830 - 27 Nov 2023
Cited by 1 | Viewed by 898
Abstract
Telomeres are nucleoprotein complexes that cap the ends of eukaryotic linear chromosomes. Telomeric DNA is bound by shelterin protein complex to prevent telomeric chromosome ends from being recognized as damaged sites for abnormal repair. To overcome the end replication problem, cancer cells mostly [...] Read more.
Telomeres are nucleoprotein complexes that cap the ends of eukaryotic linear chromosomes. Telomeric DNA is bound by shelterin protein complex to prevent telomeric chromosome ends from being recognized as damaged sites for abnormal repair. To overcome the end replication problem, cancer cells mostly preserve their telomeres by reactivating telomerase, but a minority (10–15%) of cancer cells use a homologous recombination-based pathway called alternative lengthening of telomeres (ALT). Recent studies have found that shelterin components play an important role in the ALT mechanism. The binding of TRF1, TRF2, and RAP1 to telomeres attenuates ALT activation, while the maintenance of ALT telomere requires TRF1 and TRF2. POT1 and TPP1 can also influence the occurrence of ALT. The elucidation of how shelterin regulates the initiation of ALT remains elusive. This review presents a comprehensive overview of the current findings on the regulation of ALT by shelterin components, aiming to enhance the insight into the altered functions of shelterin components in ALT cells and to identify potential targets for the treatment of ALT tumor cells. Full article
(This article belongs to the Special Issue Deployment of Proteomics Approaches in Biomedical Research)
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15 pages, 988 KiB  
Review
The Human Gastric Juice: A Promising Source for Gastric Cancer Biomarkers
by Nayra Felípez, Sheyla Montori, Naroa Mendizuri, Joan Llach, Pedro G. Delgado, Leticia Moreira, Enrique Santamaría, Joaquín Fernández-Irigoyen and Eduardo Albéniz
Int. J. Mol. Sci. 2023, 24(11), 9131; https://doi.org/10.3390/ijms24119131 - 23 May 2023
Cited by 2 | Viewed by 1726
Abstract
Gastric cancer (GC) is a major public health problem worldwide, with high mortality rates due to late diagnosis and limited treatment options. Biomarker research is essential to improve the early detection of GC. Technological advances and research methodologies have improved diagnostic tools, identifying [...] Read more.
Gastric cancer (GC) is a major public health problem worldwide, with high mortality rates due to late diagnosis and limited treatment options. Biomarker research is essential to improve the early detection of GC. Technological advances and research methodologies have improved diagnostic tools, identifying several potential biomarkers for GC, including microRNA, DNA methylation markers, and protein-based biomarkers. Although most studies have focused on identifying biomarkers in biofluids, the low specificity of these markers has limited their use in clinical practice. This is because many cancers share similar alterations and biomarkers, so obtaining them from the site of disease origin could yield more specific results. As a result, recent research efforts have shifted towards exploring gastric juice (GJ) as an alternative source for biomarker identification. Since GJ is a waste product during a gastroscopic examination, it could provide a “liquid biopsy” enriched with disease-specific biomarkers generated directly at the damaged site. Furthermore, as it contains secretions from the stomach lining, it could reflect changes associated with the developmental stage of GC. This narrative review describes some potential biomarkers for gastric cancer screening identified in gastric juice. Full article
(This article belongs to the Special Issue Deployment of Proteomics Approaches in Biomedical Research)
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