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Advances in Biomarker and Therapeutic Target Discovery in the Era of Omics Sciences

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

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 10731

Special Issue Editor


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Guest Editor
Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy
Interests: biomarkers; cancer biology; hyperhomocysteinemia; hypoxia; inflammation; neuroprotection; transglutaminase
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Special Issue Information

Dear Colleagues, 

Technological advances have led to the development of high-throughput omics approaches, which can measure thousands of biological molecules simultaneously, including nucleic acids, proteins and metabolites, in various biospecimens, such as cells, tissues and biofluids, based on the omics technology employed. The term omics encompasses multiple disciplines, such as genomics, transcriptomics, epigenomics, proteomics, metabolomics, lipidomics, nutrigenomics and microbiomics.

High-dimensional data generated by these applications from healthy and diseased samples can accelerate the rate of discovery, improve the understanding of complex diseases and support future perspectives of omics sciences, such as the discovery of diagnostic biomarkers and potential therapeutic targets.

Although the large amount of information obtained by omics applications represents a promising data source, its interpretation and insights remain an ongoing challenge for researchers. In addition, currently, specific analytical tools are designed for individual omics disciplines. However, data integration of multiomics strategies must be realized to establish a holistic understanding of molecular mechanisms involved in disease development and progression.

This Special Issue, “Advances in biomarker and therapeutic target discovery in the era of omics sciences”, welcomes original research and review articles focused on omics applications, which provide valuable insight into the identification of possible biomarkers and targets for the diagnosis and treatment of human diseases.

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

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Keywords

  • biofluids
  • biomarker
  • data analysis
  • early diagnosis
  • human disease
  • molecular pathway
  • omics
  • therapeutic target

Published Papers (5 papers)

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Research

15 pages, 1848 KiB  
Article
Blood Cell Biomarkers of Inflammation and Cytokine Levels as Predictors of Response to Biologics in Patients with Psoriasis
by Clara Sophie Bramsen Andersen, Amanda Kvist-Hansen, Mie Siewertsen, Christian Enevold, Peter Riis Hansen, Diljit Kaur-Knudsen, Claus Zachariae, Claus Henrik Nielsen, Nikolai Loft and Lone Skov
Int. J. Mol. Sci. 2023, 24(7), 6111; https://doi.org/10.3390/ijms24076111 - 24 Mar 2023
Cited by 10 | Viewed by 1734
Abstract
For people with psoriasis, biomarkers aiding in the personalization of treatment with biologics are needed. We examined the usefulness of several biomarkers of inflammation in this respect. The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune–inflammation index (SII) were measured [...] Read more.
For people with psoriasis, biomarkers aiding in the personalization of treatment with biologics are needed. We examined the usefulness of several biomarkers of inflammation in this respect. The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune–inflammation index (SII) were measured in patients with psoriasis initiating TNF-α inhibitors (n = 131), IL-17/IL-17R inhibitors (n = 65), or IL-23/IL-12/23 inhibitors (n = 50). The blood levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-17A, IL-6, soluble IL-6 receptor (sIL-6R), and soluble IL-6 signal transducer (sIL-6ST) were measured in patients initiating adalimumab (n = 62) or IL-17/IL-17R inhibitors (n = 24). Treatment response was defined by a psoriasis area and severity index (PASI) ≤ 2 three months after treatment initiation. Responders to TNF-α inhibitors had a lower NLR at baseline than non-responders (median and interquartile range (IQR) 2.15 (1.67–2.86) vs. 2.54 (1.88–3.55); p = 0.04). Responders to treatment with adalimumab had lower IL-6 levels at baseline than non-responders (0.99 (0.42–1.4) vs. 1.62 (0.96–2.41) pg/mL; p = 0.02). For the majority of patients, the IL-17A, IL-1β, and IFN-γ levels were below quantification limits. NLR and IL-6 may serve as predictive biomarkers of treatment response to TNF-α inhibitor therapy in patients with psoriasis. Full article
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17 pages, 3560 KiB  
Article
Quantitative Proteomics of Human Retinal Pigment Epithelium Reveals Key Regulators for the Pathogenesis of Age-Related Macular Degeneration
by Shichen Shen, Rebecca J. Kapphahn, Ming Zhang, Shuo Qian, Sandra R. Montezuma, Peng Shang, Deborah A. Ferrington and Jun Qu
Int. J. Mol. Sci. 2023, 24(4), 3252; https://doi.org/10.3390/ijms24043252 - 7 Feb 2023
Cited by 4 | Viewed by 2099
Abstract
Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people, with limited treatment options available for most patients. AMD involves the death of retinal pigment epithelium (RPE) and photoreceptor cells, with mitochondria dysfunction being a critical early event. In the [...] Read more.
Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people, with limited treatment options available for most patients. AMD involves the death of retinal pigment epithelium (RPE) and photoreceptor cells, with mitochondria dysfunction being a critical early event. In the current study, we utilized our unique resource of human donor RPE graded for AMD presence and severity to investigate proteome-wide dysregulation involved in early AMD. Organelle-enriched fractions of RPE were isolated from donors with early AMD (n = 45) and healthy age-matched controls (n = 32) and were analyzed by UHR-IonStar, an integrated proteomics platform enabling reliable and in-depth proteomic quantification in large cohorts. A total of 5941 proteins were quantified with excellent analytical reproducibility, and with further informatics analysis, many biological functions and pathways were found to be significantly dysregulated in donor RPE samples with early AMD. Several of these directly pinpointed changes in mitochondrial functions, e.g., translation, ATP metabolic process, lipid homeostasis, and oxidative stress. These novel findings highlighted the value of our proteomics investigation by allowing a better understanding of the molecular mechanisms underlying early AMD onset and facilitating both treatment development and biomarker discovery. Full article
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14 pages, 1990 KiB  
Article
Sorting Transcriptomics Immune Information from Tumor Molecular Features Allows Prediction of Response to Anti-PD1 Therapy in Patients with Advanced Melanoma
by Lucía Trilla-Fuertes, Angelo Gámez-Pozo, Guillermo Prado-Vázquez, Rocío López-Vacas, Andrea Zapater-Moros, Elena López-Camacho, María I. Lumbreras-Herrera, Virtudes Soriano, Fernando Garicano, Mª José Lecumberri, María Rodríguez de la Borbolla, Margarita Majem, Elisabeth Pérez-Ruiz, María González-Cao, Juana Oramas, Alejandra Magdaleno, Joaquín Fra, Alfonso Martín-Carnicero, Mónica Corral, Teresa Puértolas, Ricardo Ramos, Juan Ángel Fresno Vara and Enrique Espinosaadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2023, 24(1), 801; https://doi.org/10.3390/ijms24010801 - 2 Jan 2023
Viewed by 2582
Abstract
Immunotherapy based on anti-PD1 antibodies has improved the outcome of advanced melanoma. However, prediction of response to immunotherapy remains an unmet need in the field. Tumor PD-L1 expression, mutational burden, gene profiles and microbiome profiles have been proposed as potential markers but are [...] Read more.
Immunotherapy based on anti-PD1 antibodies has improved the outcome of advanced melanoma. However, prediction of response to immunotherapy remains an unmet need in the field. Tumor PD-L1 expression, mutational burden, gene profiles and microbiome profiles have been proposed as potential markers but are not used in clinical practice. Probabilistic graphical models and classificatory algorithms were used to classify melanoma tumor samples from a TCGA cohort. A cohort of patients with advanced melanoma treated with PD-1 inhibitors was also analyzed. We established that gene expression data can be grouped in two different layers of information: immune and molecular. In the TCGA, the molecular classification provided information on processes such as epidermis development and keratinization, melanogenesis, and extracellular space and membrane. The immune layer classification was able to distinguish between responders and non-responders to immunotherapy in an independent series of patients with advanced melanoma treated with PD-1 inhibitors. We established that the immune information is independent than molecular features of the tumors in melanoma TCGA cohort, and an immune classification of these tumors was established. This immune classification was capable to determine what patients are going to respond to immunotherapy in a new cohort of patients with advanced melanoma treated with PD-1 inhibitors Therefore, this immune signature could be useful to the clinicians to identify those patients who will respond to immunotherapy. Full article
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13 pages, 16665 KiB  
Article
Global Metabolomics Discovers Two Novel Biomarkers in Pyridoxine-Dependent Epilepsy Caused by ALDH7A1 Deficiency
by Hans-Otto Böhm, Mazyar Yazdani, Elise Mørk Sandås, Anja Østeby Vassli, Erle Kristensen, Helge Rootwelt, Hanne Bendiksen Skogvold, Eylert Brodtkorb and Katja Benedikte Prestø Elgstøen
Int. J. Mol. Sci. 2022, 23(24), 16061; https://doi.org/10.3390/ijms232416061 - 16 Dec 2022
Cited by 2 | Viewed by 1943
Abstract
Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive developmental and epileptic encephalopathy caused by pathogenic variants in the ALDH7A1 gene (PDE-ALDH7A1), which mainly has its onset in neonates and infants. Early diagnosis and treatment are crucial to prevent severe neurological sequelae or death. [...] Read more.
Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive developmental and epileptic encephalopathy caused by pathogenic variants in the ALDH7A1 gene (PDE-ALDH7A1), which mainly has its onset in neonates and infants. Early diagnosis and treatment are crucial to prevent severe neurological sequelae or death. Sensitive, specific, and stable biomarkers for diagnostic evaluations and follow-up examinations are essential to optimize outcomes. However, most of the known biomarkers for PDE lack these criteria. Additionally, there is little discussion regarding the interdependence of biomarkers in the PDE-ALDH7A1 metabolite profile. Therefore, the aim of this study was to understand the underlying mechanisms in PDE-ALDH7A1 and to discover new biomarkers in the plasma of patients using global metabolomics. Plasma samples from 9 patients with genetically confirmed PDE-ALDH7A1 and 22 carefully selected control individuals were analyzed by ultra high performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS). Two novel and reliable pyridoxine-independent diagnostic markers, 6-hydroxy-2-aminocaproic acid (HACA) and an isomer of C9H11NO4, were identified. Furthermore, a possible reaction mechanism is proposed for HACA. This study demonstrates the capability of global metabolomics in disease screening to detect established and novel biomarkers. Full article
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13 pages, 21711 KiB  
Article
Promitotic Action of Oenothera biennis on Senescent Human Dermal Fibroblasts
by Sara Ceccacci, Kévin Roger, Ines Metatla, Cerina Chhuon, Khaled Tighanimine, Stefano Fumagalli, Adriana De Lucia, Iwona Pranke, Corinne Cordier, Maria Chiara Monti and Ida Chiara Guerrera
Int. J. Mol. Sci. 2022, 23(23), 15153; https://doi.org/10.3390/ijms232315153 - 2 Dec 2022
Cited by 2 | Viewed by 1502
Abstract
Accumulation of senescent dermal fibroblasts drives skin aging. The reactivation of proliferation is one strategy to modulate cell senescence. Recently, we reported the exact chemical composition of the hydrophilic extract of Oenothera biennis cell cultures (ObHEx) and we showed its skin anti-aging properties. [...] Read more.
Accumulation of senescent dermal fibroblasts drives skin aging. The reactivation of proliferation is one strategy to modulate cell senescence. Recently, we reported the exact chemical composition of the hydrophilic extract of Oenothera biennis cell cultures (ObHEx) and we showed its skin anti-aging properties. The aim of this work is to assess its biological effect specifically on cell senescence. ObHEx action has been evaluated on normal human dermal fibroblasts subjected to stress-induced premature senescence (SIPS) through an ultra-deep proteomic analysis, leading to the most global senescence-associated proteome so far. Mass spectrometry data show that the treatment with ObHEx re-establishes levels of crucial mitotic proteins, strongly downregulated in senescent cells. To validate our proteomics findings, we proved that ObHEx can, in part, restore the activity of ‘senescence-associated-ß-galactosidase’, the most common hallmark of senescent cells. Furthermore, to assess if the upregulation of mitotic protein levels translates into a cell cycle re-entry, FACS experiments have been carried out, demonstrating a small but significative reactivation of senescent cell proliferation by ObHEx. In conclusion, the deep senescence-associated global proteome profiling published here provides a panel of hundreds of proteins deregulated by SIPS that can be used by the community to further understand senescence and the effect of new potential modulators. Moreover, proteomics analysis pointed to a specific promitotic effect of ObHEx on senescent cells. Thus, we suggest ObHEx as a powerful adjuvant against senescence associated with skin aging. Full article
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