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Application of High-Throughput Omics Sequencing in Personalized Medicine

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

Deadline for manuscript submissions: closed (28 February 2024) | Viewed by 3449

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Special Issue Editor

Dr. Touati Benoukraf

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Guest Editor

Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL A1B 3V6, Canada
Interests: genomics; epigenomics; omics interplays; microbiome; transcription factors; long-reads sequencing

Special Issue Information

Dear Colleagues,

Personalized medicine is fundamentally changing how health care is practiced. One important component of this field is the use of an individual’s omic information to offer targeted treatment, tailored to the patient. This Special Issue on “Application of High-Throughput Omics Sequencing in Personalized Medicine” welcomes original investigations, novel methodologies, and concise review manuscripts focusing on the use of omics datasets in personalized medicine, including but not limited to genomics, transcriptomics, epigenomics and microbiomics. In detail, this domain requires generation of and access to massive omics and clinical datasets, as well as adequate statistical and bioinformatics tools. Therefore, we are particularly interested in manuscripts describing integrative omics databases, “big data” analysis programs or protocols, and outputs from omics consortia. Furthermore, the generation of large datasets relies on suitable technologies such as bulk, single-cell and spatial sequencing. Thus, advances in sequencing platforms and library preparation protocols allowing the characterization of any omics landscape will be welcomed in this Special Issue. Novel or repurposed omics biomarkers for diagnosis, treatment strategies and prognosis can be considered; however, since IJMS is a molecular science journal, pure clinical or model studies will not be suitable. Nonetheless, clinical or pure model submissions with biomolecular experiments are welcomed.

Dr. Touati Benoukraf
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

omics
short-read sequencing
long-read sequencing
single-cell sequencing
screening
diagnosis
treatment strategies
algorithms
artificial intelligence
personalized medicine

Published Papers (4 papers)

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Research

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15 pages, 2146 KiB

Open AccessArticle

High-Throughput Genomics Identify Novel FBN1/2 Variants in Severe Neonatal Marfan Syndrome and Congenital Heart Defects

by Gloria K. E. Zodanu, John H. Hwang, Zubin Mehta, Carlos Sisniega, Alexander Barsegian, Xuedong Kang, Reshma Biniwale, Ming-Sing Si, Gary M. Satou, Nancy Halnon, UCLA Congenital Heart Defect BioCore Faculty, Wayne W. Grody, Glen S. Van Arsdell, Stanley F. Nelson and Marlin Touma

Int. J. Mol. Sci. 2024, 25(10), 5469; https://doi.org/10.3390/ijms25105469 - 17 May 2024

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Abstract

Fibrillin-1 and fibrillin-2, encoded by FBN1 and FBN2, respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of connective tissue disorders such as Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCD). Different genomic variations may lead to heterogeneous phenotypic features and functional consequences. Recent high-throughput sequencing modalities have allowed detection of novel variants that may guide the care for patients and inform the genetic counseling for their families. We performed clinical phenotyping for two newborn infants with complex congenital heart defects. For genetic investigations, we employed next-generation sequencing strategies including whole-genome Single-Nucleotide Polymorphism (SNP) microarray for infant A with valvular insufficiency, aortic sinus dilatation, hydronephrosis, and dysmorphic features, and Trio whole-exome sequencing (WES) for infant B with dextro-transposition of the great arteries (D-TGA) and both parents. Infant A is a term male with neonatal marfanoid features, left-sided hydronephrosis, and complex congenital heart defects including tricuspid regurgitation, aortic sinus dilatation, patent foramen ovale, patent ductus arteriosus, mitral regurgitation, tricuspid regurgitation, aortic regurgitation, and pulmonary sinus dilatation. He developed severe persistent pulmonary hypertension and worsening acute hypercapnic hypoxemic respiratory failure, and subsequently expired on day of life (DOL) 10 after compassionate extubation. Cytogenomic whole-genome SNP microarray analysis revealed a deletion within the FBN1 gene spanning exons 7–30, which overlapped with the exon deletion hotspot region associated with neonatal Marfan syndrome. Infant B is a term male prenatally diagnosed with isolated D-TGA. He required balloon atrial septostomy on DOL 0 and subsequent atrial switch operation, atrial septal defect repair, and patent ductus arteriosus ligation on DOL 5. Trio-WES revealed compound heterozygous c.518C>T and c.8230T>G variants in the FBN2 gene. Zygosity analysis confirmed each of the variants was inherited from one of the parents who were healthy heterozygous carriers. Since his cardiac repair at birth, he has been growing and developing well without any further hospitalization. Our study highlights novel FBN1/FBN2 variants and signifies the phenotype–genotype association in two infants affected with complex congenital heart defects with and without dysmorphic features. These findings speak to the importance of next-generation high-throughput genomics for novel variant detection and the phenotypic variability associated with FBN1/FBN2 variants, particularly in the neonatal period, which may significantly impact clinical care and family counseling. Full article

(This article belongs to the Special Issue Application of High-Throughput Omics Sequencing in Personalized Medicine)

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18 pages, 3109 KiB

Open AccessArticle

Development, High-Throughput Profiling, and Biopanning of a Large Phage Display Single-Domain Antibody Library

by Hee Eon Lee, Ah Hyun Cho, Jae Hyeon Hwang, Ji Woong Kim, Ha Rim Yang, Taehoon Ryu, Yushin Jung and Sukmook Lee

Int. J. Mol. Sci. 2024, 25(9), 4791; https://doi.org/10.3390/ijms25094791 - 27 Apr 2024

Viewed by 892

Abstract

Immunoglobulin G-based monoclonal antibodies (mAbs) have been effective in treating various diseases, but their large molecular size can limit their penetration of tissue and efficacy in multifactorial diseases, necessitating the exploration of alternative forms. In this study, we constructed a phage display library comprising single-domain antibodies (sdAbs; or “VHHs”), known for their small size and remarkable stability, using a total of 1.6 × 10⁹ lymphocytes collected from 20 different alpacas, resulting in approximately 7.16 × 10¹⁰ colonies. To assess the quality of the constructed library, next-generation sequencing-based high-throughput profiling was performed, analyzing approximately 5.65 × 10⁶ full-length VHH sequences, revealing 92% uniqueness and confirming the library’s diverse composition. Systematic characterization of the library revealed multiple sdAbs with high affinity for three therapeutically relevant antigens. In conclusion, our alpaca sdAb phage display library provides a versatile resource for diagnostics and therapeutics. Furthermore, the library’s vast natural VHH antibody repertoire offers insights for generating humanized synthetic sdAb libraries, further advancing sdAb-based therapeutics. Full article

(This article belongs to the Special Issue Application of High-Throughput Omics Sequencing in Personalized Medicine)

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22 pages, 5814 KiB

Open AccessArticle

Multi-System-Level Analysis with RNA-Seq on Pterygium Inflammation Discovers Association between Inflammatory Responses, Oxidative Stress, and Oxidative Phosphorylation

by Ye-Ah Kim, Yueun Choi, Tae Gi Kim, Jisu Jeong, Sanghyeon Yu, Taeyoon Kim, Kisung Sheen, Yoonsung Lee, Taesoo Choi, Yong Hwan Park, Min Seok Kang and Man S. Kim

Int. J. Mol. Sci. 2024, 25(9), 4789; https://doi.org/10.3390/ijms25094789 - 27 Apr 2024

Viewed by 509

Abstract

A pterygium is a common conjunctival degeneration and inflammatory condition. It grows onto the corneal surface or limbus, causing blurred vision and cosmetic issues. Ultraviolet is a well-known risk factor for the development of a pterygium, although its pathogenesis remains unclear, with only limited understanding of its hereditary basis. In this study, we collected RNA-seq from both pterygial tissues and conjunctival tissues (as controls) from six patients (a total of twelve biological samples) and retrieved publicly available data, including eight pterygium samples and eight controls. We investigated the intrinsic gene regulatory mechanisms closely linked to the inflammatory reactions of pterygiums and compared Asian (Korea) and the European (Germany) pterygiums using multiple analysis approaches from different perspectives. The increased expression of antioxidant genes in response to oxidative stress and DNA damage implies an association between these factors and pterygium development. Also, our comparative analysis revealed both similarities and differences between Asian and European pterygiums. The decrease in gene expressions involved in the three primary inflammatory signaling pathways—JAK/STAT, MAPK, and NF-kappa B signaling—suggests a connection between pathway dysfunction and pterygium development. We also observed relatively higher activity of autophagy and antioxidants in the Asian group, while the European group exhibited more pronounced stress responses against oxidative stress. These differences could potentially be necessitated by energy-associated pathways, specifically oxidative phosphorylation. Full article

(This article belongs to the Special Issue Application of High-Throughput Omics Sequencing in Personalized Medicine)

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Review

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20 pages, 1444 KiB

Open AccessReview

Pancreatic β-Cell Identity Change through the Lens of Single-Cell Omics Research

by Floris Leenders, Eelco J. P. de Koning and Françoise Carlotti

Int. J. Mol. Sci. 2024, 25(9), 4720; https://doi.org/10.3390/ijms25094720 - 26 Apr 2024

Viewed by 611

Abstract

The main hallmark in the development of both type 1 and type 2 diabetes is a decline in functional β-cell mass. This decline is predominantly attributed to β-cell death, although recent findings suggest that the loss of β-cell identity may also contribute to β-cell dysfunction. This phenomenon is characterized by a reduced expression of key markers associated with β-cell identity. This review delves into the insights gained from single-cell omics research specifically focused on β-cell identity. It highlights how single-cell omics based studies have uncovered an unexpected level of heterogeneity among β-cells and have facilitated the identification of distinct β-cell subpopulations through the discovery of cell surface markers, transcriptional regulators, the upregulation of stress-related genes, and alterations in chromatin activity. Furthermore, specific subsets of β-cells have been identified in diabetes, such as displaying an immature, dedifferentiated gene signature, expressing significantly lower insulin mRNA levels, and expressing increased β-cell precursor markers. Additionally, single-cell omics has increased insight into the detrimental effects of diabetes-associated conditions, including endoplasmic reticulum stress, oxidative stress, and inflammation, on β-cell identity. Lastly, this review outlines the factors that may influence the identification of β-cell subpopulations when designing and performing a single-cell omics experiment. Full article

(This article belongs to the Special Issue Application of High-Throughput Omics Sequencing in Personalized Medicine)

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