Submit to Biomedicines Review for Biomedicines Propose a Special Issue

Journal Menu

Journal Browser

The Human Proteome in Disease, Diagnostics and Translation into Precision Medicine: Current Status and Future Prospects

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular Genetics and Genetic Diseases".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 12846

Share This Special Issue

Special Issue Editor

Dr. M. Walid Qoronfleh

E-Mail Website
Guest Editor

1. Q3 Research Institute (QRI), Research & Policy Division, Ann Arbor, MI 48197, USA
2. Consulting Services Department, 21 HealthStreet, London SW16 3JY, UK
Interests: precision medicine; drug discovery; biotechnology; functional genomics; proteomics; biomarkers; companion diagnostics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It gives us great pleasure to invite researchers and scientists to this MDPI Special Issue by Biomedicines, which focuses on the human proteome in health, disease and therapy. Proteins are the primary functional effectors in human biology and are involved in health and diseases. The human proteoforms are rich and deciphering their structure/function is critical to both basic and translational research. It is very fitting and timely to launch this Special Issue as we celebrate 20 years of human proteome accomplishments and prepare for the next generation of advancements.

Since the inception of the Human Proteome organization (HUPO) and its first World Congress in November 2002, the stated visionary goal has been translating the code of life. The HUPO international, collaborative initiative ‘The Human Proteome Project (HPP)’ (a Grand Challenge Project, “A Function for Each Protein”) aims to transform our knowledge of the human proteome and map it in its entirety, systematically utilizing state-of-the-art proteomics methods and software, available platform technologies and emerging techniques. Undoubtedly, this will not only enhance our holistic understanding of human biology at the cellular/molecular levels but will also establish a foundation for the development of diagnostic, prognostic, therapeutic, and preventive medical applications.

The HPP is better coordinated and more focused. Nowadays, the HPP comprises two strategic initiatives—chromosome-centric (C-HPP) and biology/disease-centric (B/D-HPP). To date, protein expression has now been credibly detected for 93.2% of the predicted proteins encoded in the human genome. Conversely, the number of proteins in existence (missing proteins) has been reduced.

For marking the human proteome achievements, this Biomedicines’ Special Issue aims to contribute to the knowledge of the human proteome and will describe the following:

Application of proteomics in a variety of biological and clinical studies;
Cutting-edge technologies, techniques and analytical tools in proteomics;
Integration with other ‘omics’ platforms;
Recent progress in biology and disease-driven proteome knowledge;
Emergence of translational activities from protein profiling;
Discerning protein structure/function and molecular processes;
Protein expression including sequence variants and splice variants, post-translational modification, sub-cellular localization, physiology and pathologies;
Protein–protein interactions, molecular pathways and networks (interactomics);
Protein therapeutic targets discovery, validation, drug discovery, biomarkers and companion diagnostics ;
Current trends in computational biology, bioinformatics and databases associated with the human proteome;
Precision and translational medicine of human proteome.

Dr. M. Walid Qoronfleh
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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

proteomics
human proteome
systems biology
precision medicine
biomarker
disease pathogenesis
diagnostics
mass spectrometry
multiplex protein analysis
protein network
splice variants
post-translational modifications
omics analysis
data integration

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (8 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

13 pages, 2654 KiB

Open AccessCommunication

Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals

by Alexey S. Kononikhin, Natalia L. Starodubtseva, Alexander G. Brzhozovskiy, Alisa O. Tokareva, Daria N. Kashirina, Natalia V. Zakharova, Anna E. Bugrova, Maria I. Indeykina, Liudmila Kh. Pastushkova, Irina M. Larina, Vladimir A. Mitkevich, Alexander A. Makarov and Evgeny N. Nikolaev

Biomedicines 2024, 12(10), 2403; https://doi.org/10.3390/biomedicines12102403 - 21 Oct 2024

Viewed by 966

Abstract

Background/Objectives: The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue. Methods: In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort. Results: The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples. The quantified proteins included 66 FDA-approved markers of cardiovascular diseases (CVD), and other potential biomarkers of pathologies such as cancer, diabetes mellitus, and Alzheimer’s disease. The analysis of individual variations of the plasma proteins revealed significant differences between the male (11) and female (10) groups. In total, fifteen proteins had a significantly different concentration in plasma; this included four proteins that exhibited changes greater than ±1.5-fold, three proteins (RBP4, APCS, and TTR) with higher levels in males, and one (SHBG) elevated in females. The obtained results demonstrated considerable agreement with the data collected from 20 samples of a North American cohort, which were analyzed with the similar MRM assay. The most significant differences between the cohorts of the two continents were observed in the level of 42 plasma proteins (including 24 FDA markers), of which 17 proteins showed a ≥1.5-fold change, and included proteins increased in North Americans (APOB, CRTAC1, C1QB, C1QC, C9, CRP, HP, IGHG1, IGKV4-1, SERPING1, RBP4, and AZGP1), as well as those elevated in Europeans (APOF, CD5L, HBG2, SELPLG, and TNA). Conclusions: The results suggest a different contribution of specific (patho)physiological pathways (e.g., immune system and blood coagulation) to the development of socially significant diseases in Europeans and North Americans, and they should be taken into account when refining diagnostic panels. Full article

(This article belongs to the Special Issue The Human Proteome in Disease, Diagnostics and Translation into Precision Medicine: Current Status and Future Prospects)

► Show Figures

Figure 1

20 pages, 21711 KiB

Open AccessArticle

Use of a Novel Whole Blood Separation and Transport Device for Targeted and Untargeted Proteomics

by Colin T. McDowell, Amanda L. Weaver, Nylev Vargas-Cruz, Nathan K. Kaiser, Charles M. Nichols and Gary A. Pestano

Biomedicines 2024, 12(10), 2318; https://doi.org/10.3390/biomedicines12102318 - 11 Oct 2024

Viewed by 970

Abstract

Background: There is significant interest in developing alternatives to traditional blood transportation and separation methods, which often require centrifugation and cold storage to preserve specimen integrity. Here we provide new performance findings that characterize a novel device that separates whole blood via lateral flow then dries the isolated components for room temperature storage and transport. Methods: Untargeted proteomics was performed on non-small cell lung cancer (NSCLC) and normal healthy plasma applied to the device or prepared neat. Results: Significantly, proteomic profiles from the storage device were more reproducible than from neat plasma. Proteins depleted or absent in the device preparation were shown to be absorbed onto the device membrane through largely hydrophilic interactions. Use of the device did not impact proteins relevant to an NSCLC clinical immune classifier. The device was also evaluated for use in targeted proteomics experiments using multiple-reaction monitoring (MRM) mass spectrometry. Intra-specimen detection intensity for protein targets between neat and device preparations showed a strong correlation, and device variation was comparable to the neat after normalization. Inter-specimen measurements between the device and neat preparations were also highly concordant. Conclusions: These studies demonstrate that the lateral flow device is a viable blood separation and transportation tool for untargeted and targeted proteomics applications. Full article

(This article belongs to the Special Issue The Human Proteome in Disease, Diagnostics and Translation into Precision Medicine: Current Status and Future Prospects)

► Show Figures

Graphical abstract

21 pages, 4460 KiB

Open AccessArticle

A Multiplexed Quantitative Proteomics Approach to the Human Plasma Protein Signature

by Estefanía Núñez, María Gómez-Serrano, Enrique Calvo, Elena Bonzon-Kulichenko, Marco Trevisan-Herraz, José Manuel Rodríguez, Fernando García-Marqués, Ricardo Magni, Enrique Lara-Pezzi, José Luis Martín-Ventura, Emilio Camafeita and Jesús Vázquez

Biomedicines 2024, 12(9), 2118; https://doi.org/10.3390/biomedicines12092118 - 18 Sep 2024

Viewed by 1143

Abstract

Despite the plasma proteome being able to provide a unique insight into the health and disease status of individuals, holding singular promise as a source of protein biomarkers that could be pivotal in the context of personalized medicine, only around 100 proteins covering a few human conditions have been approved as biomarkers by the US Food and Drug Administration (FDA) so far. Mass spectrometry (MS) currently has enormous potential for high-throughput analysis in clinical research; however, plasma proteomics remains challenging mainly due to the wide dynamic range of plasma protein abundances and the time-consuming procedures required. We applied a new MS-based multiplexed proteomics workflow to quantitate proteins, encompassing 67 FDA-approved biomarkers, in >1300 human plasma samples from a clinical cohort. Our results indicate that this workflow is suitable for large-scale clinical studies, showing good accuracy and reproducibility (coefficient of variation (CV) < 20 for 90% of the proteins). Furthermore, we identified plasma signature proteins (stable in time on an individual basis), stable proteins (exhibiting low biological variability and high temporal stability), and highly variable proteins (with low temporal stability) that can be used for personalized health monitoring and medicine. Full article

(This article belongs to the Special Issue The Human Proteome in Disease, Diagnostics and Translation into Precision Medicine: Current Status and Future Prospects)

► Show Figures

Figure 1

15 pages, 3178 KiB

Open AccessArticle

Proteomic Characterisation of Heart Failure Reveals a Unique Molecular Phenotype for Hypertrophic Cardiomyopathy

by Claire Tonry, Katie Linden, Patrick Collier, Mark Ledwidge, Ken McDonald, Ben C. Collins and Chris J. Watson

Biomedicines 2024, 12(8), 1712; https://doi.org/10.3390/biomedicines12081712 - 1 Aug 2024

Viewed by 1031

Abstract

Hypertrophic cardiomyopathy (HCM) is a disease, which is difficult to diagnose at an early stage and for which there is a pressing need for more effective treatment options. The purpose of this study was to compare the molecular profile of HCM to that of ischaemic cardiomyopathy (ISCM) and dilated cardiomyopathy (DCM) for identification of protein and pathway targets that could support the development of better diagnostic and treatment options for HCM. A high-throughput mass spectrometry workflow was applied to achieve deep quantitative coverage of left ventricular tissue from HCM, DCM, ISCM and non-heart-failure control patients. HCM had a diverse proteomic profile compared to that of DCM and ISCM. Differentially expressed proteins unique to HCM were identified based on an observed fold change of ≥1.5 or ≤0.67 and q-value ≤ 0.05. Candidate proteins of interest were found to be significantly associated with clinical features of HCM. The significant association between these proteins and HCM was validated in an independent dataset. This represents one of the largest and deepest proteomic datasets for myocardial tissue reported to date. The dataset highlights the diverse proteomic profile of HCM, relative to other cardiomyopathies, and reveals disease-relevant pathways and promising biomarker candidates that are uniquely associated with HCM. Full article

(This article belongs to the Special Issue The Human Proteome in Disease, Diagnostics and Translation into Precision Medicine: Current Status and Future Prospects)

► Show Figures

Figure 1

17 pages, 2641 KiB

Open AccessArticle

Plasma Proteomics Elucidated a Protein Signature in COVID-19 Patients with Comorbidities and Early-Diagnosis Biomarkers

by Víctor Urbiola-Salvador, Suiane Lima de Souza, Katarzyna Macur, Paulina Czaplewska and Zhi Chen

Biomedicines 2024, 12(4), 840; https://doi.org/10.3390/biomedicines12040840 - 10 Apr 2024

Viewed by 1671

Abstract

Despite great scientific efforts, deep understanding of coronavirus-19 disease (COVID-19) immunopathology and clinical biomarkers remains a challenge. Pre-existing comorbidities increase the mortality rate and aggravate the exacerbated immune response against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which can result in more severe symptoms as well as long-COVID and post-COVID complications. In this study, we applied proteomics analysis of plasma samples from 28 patients with SARS-CoV-2, with and without pre-existing comorbidities, as well as their corresponding controls to determine the systemic protein changes caused by the SARS-CoV-2 infection. As a result, the protein signature shared amongst COVID-19 patients with comorbidities was revealed to be characterized by alterations in the coagulation and complement pathways, acute-phase response proteins, tissue damage and remodeling, as well as cholesterol metabolism. These altered proteins may play a relevant role in COVID-19 pathophysiology. Moreover, several novel potential biomarkers for early diagnosis of the SARS-CoV-2 infection were detected, such as increased levels of keratin K22E, extracellular matrix protein-1 (ECM1), and acute-phase response protein α-2-antiplasmin (A2AP). Importantly, elevated A2AP may contribute to persistent clotting complications associated with the long-COVID syndrome in patients with comorbidities. This study provides new insights into COVID-19 pathogenesis and proposes novel potential biomarkers for early diagnosis that could be facilitated for clinical application by further validation studies. Full article

(This article belongs to the Special Issue The Human Proteome in Disease, Diagnostics and Translation into Precision Medicine: Current Status and Future Prospects)

► Show Figures

Figure 1

16 pages, 4559 KiB

Open AccessArticle

Comparative Efficacy of Metformin and Glimepiride in Modulating Pharmacological Network to Increase BDNF Levels and Benefit Type 2 Diabetes-Related Cognitive Impairment

by Athira Anirudhan, Sheikh F. Ahmad, Talha Bin Emran, Paola Isabel Angulo-Bejarano, Ashutosh Sharma and Shiek S. S. J. Ahmed

Biomedicines 2023, 11(11), 2939; https://doi.org/10.3390/biomedicines11112939 - 31 Oct 2023

Cited by 4 | Viewed by 2235

Abstract

Cognitive impairment is anotable complication of type 2 diabetes (T2DM), accompanied by reduced brain-derived neurotrophic factor (BDNF) in the brain and blood. Anti-diabetic drugs reduce hyperglycemia, yet their effect on cognitive improvement is unknown. We aimed to investigate the effect of anti-diabetic drugs regulating BDNF in T2DM through computational and case-control study design. We obtained T2DMproteins viatext-mining to construct a T2DMprotein network. From the T2DMnetwork, the metformin and glimepiride interactomes and their crucial shortest-path-stimulating BDNF were identified. Using qRTPCR, the genes encoding the shortest-path proteins were assessed in four groups (untreated-T2DM, metformin-treated, glimepiride-treated, and healthy controls). Finally, ELISA was used to assess serum BDNF levels to validate drug efficacy. As a result of this investigation, aT2DMnetwork was constructed with 3683 text-mined proteins. Then, the T2DMnetwork was explored to generate a metformin and glimepiride interactome that establishes the critical shortest-path for BDNF stimulation. Metformin stimulates BDNF via APP binding to the PRKAB1 receptor. Whereas, glimepiride increases BDNF by binding to KCNJ11 via AP2M1 and ESR1 proteins. Both drug shortest-path encoding genes differed significantly between the groups. Unlike metformin, BDNF gene and protein expression rise significantly with glimepiride. Overall, glimepiride can effectively increase BDNF, which could benefit T2DM patients with cognitive deterioration. Full article

(This article belongs to the Special Issue The Human Proteome in Disease, Diagnostics and Translation into Precision Medicine: Current Status and Future Prospects)

► Show Figures

Figure 1

14 pages, 1676 KiB

Open AccessArticle

Pharmacometabolomic Approach to Investigate the Response to Metformin in Patients with Type 2 Diabetes: A Cross-Sectional Study

by Khaled Naja, Najeha Anwardeen, Moustafa Al-Hariri, Asmaa A. Al Thani and Mohamed A. Elrayess

Biomedicines 2023, 11(8), 2164; https://doi.org/10.3390/biomedicines11082164 - 1 Aug 2023

Cited by 3 | Viewed by 1903

Abstract

Metformin constitutes the foundation therapy in type 2 diabetes (T2D). Despite its multiple beneficial effects and widespread use, there is considerable inter-individual variability in response to metformin. Our objective is to identify metabolic signatures associated with poor and good responses to metformin, which may improve our ability to predict outcomes for metformin treatment. In this cross-sectional study, clinical and metabolic data for 119 patients with type 2 diabetes taking metformin were collected from the Qatar Biobank. Patients were empirically dichotomized according to their HbA_1C levels into good and poor responders. Differences in the level of metabolites between these two groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. Good responders showed increased levels of sphingomyelins, acylcholines, and glutathione metabolites. On the other hand, poor responders showed increased levels of metabolites resulting from glucose metabolism and gut microbiota metabolites. The results of this study have the potential to increase our knowledge of patient response variability to metformin and carry significant implications for enabling personalized medicine. Full article

(This article belongs to the Special Issue The Human Proteome in Disease, Diagnostics and Translation into Precision Medicine: Current Status and Future Prospects)

► Show Figures

Figure 1

Review

Jump to: Research

16 pages, 675 KiB

Open AccessReview

Chronic Pelvic Pain, Vulvar Pain Disorders, and Proteomics Profiles: New Discoveries, New Hopes

by Chiara Di Tucci and Ludovico Muzii

Biomedicines 2024, 12(1), 1; https://doi.org/10.3390/biomedicines12010001 - 19 Dec 2023

Cited by 3 | Viewed by 1839

Abstract

Chronic pelvic pain (CPP) is generally defined as non-cyclic pain perceived in the pelvic area that has persisted from three to six months or longer and is unrelated to pregnancy. The etiology of CPP is complex, multifactorial, with heterogeneous presentation, and includes several diseases such as endometriosis, adenomyosis, and interstitial cystitis/bladder pain syndrome. It may also be associated with sexual dysfunction, musculoskeletal disorders, and comorbid psychiatric symptoms. Vulvar pain disorders (VPDs) are typically categorized separately from chronic pelvic pain; among all VPDs, vulvodynia is a chronic vulvar pain of unknown etiology, lasting at least 3 months and that might be associated with other potentially linked factors. Proteomics represents a useful approach to study the proteome profiles of clinical samples. In this review, we have considered a selection of articles that have analyzed the protein abundance and novel protein species from various biological samples, including eutopic/ectopic endometrium, urine, serum, follicular, peritoneal fluid, and cervical mucus, potentially involved in the pathogenesis and progression of CPP and VPDs. These findings could represent valuable targets for paving the way for the differential diagnosis and therapeutic management of CPP and VDPs, thereby optimizing both the prevention and treatment of these conditions. Full article

(This article belongs to the Special Issue The Human Proteome in Disease, Diagnostics and Translation into Precision Medicine: Current Status and Future Prospects)

► Show Figures

Journal Menu

Journal Browser

The Human Proteome in Disease, Diagnostics and Translation into Precision Medicine: Current Status and Future Prospects

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI