Nanopore Sequencing and Its Clinical Applications

Sun, Xiang; Song, Lei; Yang, Wenjuan; Zhang, Lili; Li, Meng; Li, Xiaoshuang; Tian, Geng; Wang, Weiwei

doi:10.1007/978-1-0716-0904-0_2

Cited by 15 publications

(13 citation statements)

References 36 publications

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“…Although the detection of CoQ10 biosynthesis and MRC activity have some diagnostic value, their clinical utility for COQ10D7 diagnosis is limited because of the invasive sampling, relatively long turnaround time for cell culture, limited data regarding diagnostic accuracy, and the lack of a consensus or comprehensive evaluation of detection methodologies. Therefore, genetic testing, particularly highthroughput sequencing, either whole exome and genomebased, should be used as the first-line tool to diagnose COQ10D7 in a rapid and definitive manner, especially when point-of-care high-throughput sequencing is available (Sun, et al, 2020;Sanford, et al, 2019). In fact, all reported COQ4 variants were diagnosed using WES.…”

Section: Biochemical Analysesmentioning

confidence: 99%

Primary Coenzyme Q10 Deficiency-7 and Pathogenic COQ4 Variants: Clinical Presentation, Biochemical Analyses, and Treatment

2022

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Primary Coenzyme Q10 Deficiency-7 (COQ10D7) is a rare mitochondrial disorder caused by pathogenic COQ4 variants. In this review, we discuss the correlation of COQ4 genotypes, particularly the East Asian-specific c.370G > A variant, with the clinical presentations and therapeutic effectiveness of coenzyme Q10 supplementation from an exon-dependent perspective. Pathogenic COQ4 variants in exons 1–4 are associated with less life-threating presentations, late onset, responsiveness to CoQ10 therapy, and a relatively long lifespan. In contrast, pathogenic COQ4 variants in exons 5–7 are associated with early onset, unresponsiveness to CoQ10 therapy, and early death and are more fatal. Patients with the East Asian-specific c.370G > A variant displays intermediate disease severity with multi-systemic dysfunction, which is between that of the patients with variants in exons 1–4 and 5–7. The mechanism underlying this exon-dependent genotype-phenotype correlation may be associated with the structure and function of COQ4. Sex is shown unlikely to be associated with disease severity. While point-of-care high-throughput sequencing would be useful for the rapid diagnosis of pathogenic COQ4 variants, whereas biochemical analyses of the characteristic impairments in CoQ10 biosynthesis and mitochondrial respiratory chain activity, as well as the phenotypic rescue of the CoQ10 treatment, are necessary to confirm the pathogenicity of suspicious variants. In addition to CoQ10 derivatives, targeted drugs and gene therapy could be useful treatments for COQ10D7 depending on the in-depth functional investigations and the development of gene editing technologies. This review provides a fundamental reference for the sub-classification of COQ10D7 and aim to advance our knowledge of the pathogenesis, clinical diagnosis, and prognosis of this disease and possible interventions.

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Section: Biochemical Analysesmentioning

confidence: 99%

Primary Coenzyme Q10 Deficiency-7 and Pathogenic COQ4 Variants: Clinical Presentation, Biochemical Analyses, and Treatment

2022

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“…It is conceivable that the ONT and PacBio platforms are unsuitable for measuring interstrand crosslinks because they are both sequencing single-stranded DNA. Therefore, efforts and developments are on the way to use wider pores to perform sequencing of double-stranded DNA [109][110][111]. Crosslinks of DNA to whole proteins will probably not work with this new technology.…”

Section: Single Molecule Dna Sequencingmentioning

confidence: 99%

Current and Future Methodology for Quantitation and Site-Specific Mapping the Location of DNA Adducts

Boysen

Nookaew

2022

Toxics

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Formation of DNA adducts is a key event for a genotoxic mode of action, and their presence is often used as a surrogate for mutation and increased cancer risk. Interest in DNA adducts are twofold: first, to demonstrate exposure, and second, to link DNA adduct location to subsequent mutations or altered gene regulation. Methods have been established to quantitate DNA adducts with high chemical specificity and to visualize the location of DNA adducts, and elegant bio-analytical methods have been devised utilizing enzymes, various chemistries, and molecular biology methods. Traditionally, these highly specific methods cannot be combined, and the results are incomparable. Initially developed for single-molecule DNA sequencing, nanopore-type technologies are expected to enable simultaneous quantitation and location of DNA adducts across the genome. Herein, we briefly summarize the current methodologies for state-of-the-art quantitation of DNA adduct levels and mapping of DNA adducts and describe novel single-molecule DNA sequencing technologies to achieve both measures. Emerging technologies are expected to soon provide a comprehensive picture of the exposome and identify gene regions susceptible to DNA adduct formation.

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“… 105 – 107 Therefore, nanopore technology was able to detect and analyze single-molecule amino acid, DNA, RNA, as well as long nucleotide sequences with modifications including methylation sites. 108 The application of nanopore sequencing was applied in the detection and characterization of chromosomal translocations in AML recently. 109 …”

Section: Cutting-edge Technologies Facilitate the Study Of Small Ncrn...mentioning

confidence: 99%

Small noncoding RNAs play superior roles in maintaining hematopoietic stem cell homeostasis

et al. 2022

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The maintenance of the mammalian blood system depends on hematopoietic stem cells (HSCs), which are a rare class of adult stem cells with self-renewal and multilineage differentiation capacities. The homeostasis of hematopoietic stem cells is finely tuned by a variety of endogenous and exogenous regulatory factors, and disrupted balance will lead to hematological diseases including leukemia and anemia. Recently, emerging studies have illustrated the cellular and molecular mechanisms underlying the regulation of HSC homeostasis. Particularly, the rapid development of second-generation sequencing technologies has uncovered that many small noncoding RNAs (ncRNAs) are highly expressed in HSCs, including snoRNAs, miRNAs, tsRNAs, circular RNAs, etc. In this study, we will summarize the essential roles and regulatory mechanisms of these small ncRNAs in maintaining HSC homeostasis. Overall, this review provides up-to-date information in the regulation of HSC homeostasis by small ncRNAs, which sheds light into the development of therapeutic strategies against hematopoietic malignancies.

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Nanopore Sequencing and Its Clinical Applications

Cited by 15 publications

References 36 publications

Primary Coenzyme Q10 Deficiency-7 and Pathogenic COQ4 Variants: Clinical Presentation, Biochemical Analyses, and Treatment

Primary Coenzyme Q10 Deficiency-7 and Pathogenic COQ4 Variants: Clinical Presentation, Biochemical Analyses, and Treatment

Current and Future Methodology for Quantitation and Site-Specific Mapping the Location of DNA Adducts

Small noncoding RNAs play superior roles in maintaining hematopoietic stem cell homeostasis

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