ijms-logo

Journal Browser

Journal Browser

Towards Precision Prognostication and Personalized Therapeutics through Proteomics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 10959

Special Issue Editor

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

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, posttranslational 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 highlighting the progress of proteomic methodologies in the implementation phases of personalized medicine. This open access 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 welcomed.

Dr. Enrique Santamaría
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
  • posttranslational modifications
  • biomarker detection
  • patient stratification
  • network biology
  • proteostasis
  • multi-omic data integration

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research

3 pages, 210 KiB  
Editorial
Towards Precision Prognostication and Personalized Therapeutics through Proteomics
by Enrique Santamaría
Int. J. Mol. Sci. 2023, 24(7), 6361; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076361 - 28 Mar 2023
Viewed by 661
Abstract
Next-generation proteomics has allowed the implementation of biomedical proteome research to uncover disease-affected protein expression profiles [...] Full article

Research

Jump to: Editorial

18 pages, 3216 KiB  
Article
Altered Cortical Palmitoylation Induces Widespread Molecular Disturbances in Parkinson’s Disease
by Juan F. Cervilla-Martínez, Juan J. Rodríguez-Gotor, Krzysztof J. Wypijewski, Ángela Fontán-Lozano, Tao Wang, Enrique Santamaría, William Fuller and Rebeca Mejías
Int. J. Mol. Sci. 2022, 23(22), 14018; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232214018 - 14 Nov 2022
Cited by 7 | Viewed by 2073
Abstract
The relationship between Parkinson’s disease (PD), the second-most common neurodegenerative disease after Alzheimer’s disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, to better understand the role of protein palmitoylation in PD and the pathways altered in this [...] Read more.
The relationship between Parkinson’s disease (PD), the second-most common neurodegenerative disease after Alzheimer’s disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, to better understand the role of protein palmitoylation in PD and the pathways altered in this disease, we analyzed the differential palmitoyl proteome (palmitome) in the cerebral cortex of PD patients compared to controls (n = 4 per group). Data-mining of the cortical palmitome from PD patients and controls allowed us to: (i) detect a set of 150 proteins with altered palmitoylation in PD subjects in comparison with controls; (ii) describe the biological pathways and targets predicted to be altered by these palmitoylation changes; and (iii) depict the overlap between the differential palmitome identified in our study with protein interactomes of the PD-linked proteins α-synuclein, LRRK2, DJ-1, PINK1, GBA and UCHL1. In summary, we partially characterized the altered palmitome in the cortex of PD patients, which is predicted to impact cytoskeleton, mitochondrial and fibrinogen functions, as well as cell survival. Our study suggests that protein palmitoylation could have a role in the pathophysiology of PD, and that comprehensive palmitoyl-proteomics offers a powerful approach for elucidating novel cellular pathways modulated in this neurodegenerative disease. Full article
Show Figures

Figure 1

16 pages, 2278 KiB  
Article
diaPASEF Proteomics and Feature Selection for the Description of Sputum Proteome Profiles in a Cohort of Different Subtypes of Lung Cancer Patients and Controls
by María del Sol Arenas-De Larriva, Alejandro Fernández-Vega, Bernabe Jurado-Gamez and Ignacio Ortea
Int. J. Mol. Sci. 2022, 23(15), 8737; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158737 - 05 Aug 2022
Cited by 3 | Viewed by 2014
Abstract
The high mortality, the presence of an initial asymptomatic stage and the fact that diagnosis in early stages reduces mortality justify the implementation of screening programs in the populations at risk of lung cancer. It is imperative to develop less aggressive methods that [...] Read more.
The high mortality, the presence of an initial asymptomatic stage and the fact that diagnosis in early stages reduces mortality justify the implementation of screening programs in the populations at risk of lung cancer. It is imperative to develop less aggressive methods that can complement existing diagnosis technologies. In this study, we aimed to identify lung cancer protein biomarkers and pathways affected in sputum samples, using the recently developed diaPASEF mass spectrometry (MS) acquisition mode. The sputum proteome of lung cancer cases and controls was analyzed through nano-HPLC–MS using the diaPASEF mode. For functional analysis, the results from differential expression analysis were further analyzed in the STRING platform, and feature selection was performed using sparse partial least squares discriminant analysis (sPLS-DA). Our results showed an activation of inflammation, with an alteration of pathways and processes related to acute-phase, complement, and immune responses. The resulting sPLS-DA model separated between case and control groups with high levels of sensitivity and specificity. In conclusion, we showed how new-generation proteomics can be used to detect potential biomarkers in sputum samples, and ultimately to discriminate patients from controls and even to help to differentiate between different cancer subtypes. Full article
Show Figures

Figure 1

12 pages, 2572 KiB  
Article
Mitochondrial Oxidative Stress Induces Cardiac Fibrosis in Obese Rats through Modulation of Transthyretin
by Ernesto Martínez-Martínez, Joaquín Fernández-Irigoyen, Enrique Santamaría, María Luisa Nieto, José Manuel Bravo-San Pedro and Victoria Cachofeiro
Int. J. Mol. Sci. 2022, 23(15), 8080; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158080 - 22 Jul 2022
Cited by 3 | Viewed by 1563
Abstract
A proteomic approach was used to characterize potential mediators involved in the improvement in cardiac fibrosis observed with the administration of the mitochondrial antioxidant MitoQ in obese rats. Male Wistar rats were fed a standard diet (3.5% fat; CT) or a high-fat diet [...] Read more.
A proteomic approach was used to characterize potential mediators involved in the improvement in cardiac fibrosis observed with the administration of the mitochondrial antioxidant MitoQ in obese rats. Male Wistar rats were fed a standard diet (3.5% fat; CT) or a high-fat diet (35% fat; HFD) and treated with vehicle or MitoQ (200 μM) in drinking water for 7 weeks. Obesity modulated the expression of 33 proteins as compared with controls of the more than 1000 proteins identified. These include proteins related to endoplasmic reticulum (ER) stress and oxidative stress. Proteomic analyses revealed that HFD animals presented with an increase in cardiac transthyretin (TTR) protein levels, an effect that was prevented by MitoQ treatment in obese animals. This was confirmed by plasma levels, which were associated with those of cardiac levels of both binding immunoglobulin protein (BiP), a marker of ER stress, and fibrosis. TTR stimulated collagen I production and BiP in cardiac fibroblasts. This upregulation was prevented by the presence of MitoQ. In summary, the results suggest a role of TTR in cardiac fibrosis development associated with obesity and the beneficial effects of treatment with mitochondrial antioxidants. Full article
Show Figures

Figure 1

14 pages, 3388 KiB  
Article
Longitudinal Proteomic Analysis of Plasma across Healthy Pregnancies Reveals Indicators of Gestational Age
by Elizabeth Yohannes, Danielle L. Ippolito, Jennifer R. Damicis, Elisabeth M. Dornisch, Katherine M. Leonard, Peter G. Napolitano and Nicholas Ieronimakis
Int. J. Mol. Sci. 2022, 23(13), 7076; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137076 - 25 Jun 2022
Cited by 1 | Viewed by 1595
Abstract
Longitudinal changes in the blood proteome during gestation relate to fetal development and maternal homeostasis. Charting the maternal blood proteome in normal pregnancies is critical for establishing a baseline reference when assessing complications and disease. Using mass spectrometry-based shotgun proteomics, we surveyed the [...] Read more.
Longitudinal changes in the blood proteome during gestation relate to fetal development and maternal homeostasis. Charting the maternal blood proteome in normal pregnancies is critical for establishing a baseline reference when assessing complications and disease. Using mass spectrometry-based shotgun proteomics, we surveyed the maternal plasma proteome across uncomplicated pregnancies. Results indicate a significant rise in proteins that govern placentation and are vital to the development and health of the fetus. Importantly, we uncovered proteome signatures that strongly correlated with gestational age. Fold increases and correlations between the plasma concentrations of ADAM12 (ρ = 0.973), PSG1 (ρ = 0.936), and/or CSH1/2 (ρ = 0.928) with gestational age were validated with ELISA. Proteomic and validation analyses demonstrate that the maternal plasma concentration of ADAM12, either independently or in combination with either PSG1 or CSH1/2, correlates with gestational age within ±8 days throughout pregnancy. These findings suggest that the gestational age in healthy pregnancies may be determined by referencing the concentration of select plasma proteins. Full article
Show Figures

Figure 1

13 pages, 1597 KiB  
Article
Absolute Quantification of Nav1.5 Expression by Targeted Mass Spectrometry
by Sarah L. Adams, Ge Chang, Mohamed A. Fouda, Sharwan Kumar and Bingyun Sun
Int. J. Mol. Sci. 2022, 23(8), 4177; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084177 - 10 Apr 2022
Cited by 3 | Viewed by 2309
Abstract
Nav1.5 is the pore forming α-subunit of the cardiac voltage-gated sodium channel that initiates cardiac action potential and regulates the human heartbeat. A normal level of Nav1.5 is crucial to cardiac function and health. Over- or under-expression of Nav1.5 can cause various cardiac [...] Read more.
Nav1.5 is the pore forming α-subunit of the cardiac voltage-gated sodium channel that initiates cardiac action potential and regulates the human heartbeat. A normal level of Nav1.5 is crucial to cardiac function and health. Over- or under-expression of Nav1.5 can cause various cardiac diseases ranging from short PR intervals to Brugada syndromes. An assay that can directly quantify the protein amount in biological samples would be a priori to accurately diagnose and treat Nav1.5-associated cardiac diseases. Due to its large size (>200 KD), multipass transmembrane domains (24 transmembrane passes), and heavy modifications, Nav1.5 poses special quantitation challenges. To date, only the relative quantities of this protein have been measured in biological samples. Here, we describe the first targeted and mass spectrometry (MS)-based quantitative assay that can provide the copy numbers of Nav1.5 in cells with a well-defined lower limit of quantification (LLOQ) and precision. Applying the developed assay, we successfully quantified transiently expressed Nav1.5 in as few as 1.5 million Chinese hamster ovary (CHO) cells. The obtained quantity was 3 ± 2 fmol on the column and 3 ± 2 × 104 copies/cell. To our knowledge, this is the first absolute quantity of Nav1.5 measured in a biological sample. Full article
Show Figures

Graphical abstract

Back to TopTop