RNA sequencing role and application in clinical diagnostic

Peymani, Fatemeh; Farzeen, Aiman; Prokisch, Holger

doi:10.1002/ped4.12314

Cited by 15 publications

(7 citation statements)

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“…The rapid advances in high-throughput sequencing has greatly improved our knowledge of the molecular mechanisms underlying carcinogenesis [ 26 , 27 ]. In the present study, by analyzing a publicly available RNA-sequencing datasets from the GEO database, ZCCHC12 was found overexpressed in OS tissues than adjacent non-tumor samples.…”

Section: Discussionmentioning

confidence: 99%

ZCCHC12 promotes the progression of osteosarcoma via PI3K/AKT pathway

Cui

Dong

2022

Aging

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Researchers have reported that zinc finger CCHC domain containing 12 gene (ZCCHC12) plays a role in the progression and tumorigenesis of papillary thyroid cancer. However, the biological role of ZCCHC12 in osteosarcoma (OS) remains unknown. ZCCHC12 was highly upregulated in OS cell lines according to our present study. Also, our subsequent assays demonstrated that ZCCHC12 enhanced the proliferation, tumor growth and migration of OS cells. Moreover, the epithelial-mesenchymal transition (EMT) of OS cells was also promoted by ZCCHC12. In addition, downregulation of ZCCHC12 induced apoptosis and S-phase arrest in OS cells. Then, our study indicated that ZCCHC12 exerts its oncogenic function in OS cells by activating the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway greatly limits the oncogenic function of ZCCHC12 in OS cells. Also, overexpression of ZCCHC12 promotes tumor growth in vivo. Altogether, our study suggests ZCCHC12 promotes OS cells progression by activating the PI3K/AKT pathway. The ZCCHC12 gene may be a novel diagnostic and therapeutic target for OS.

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Section: Discussionmentioning

confidence: 99%

ZCCHC12 promotes the progression of osteosarcoma via PI3K/AKT pathway

Cui

Dong

2022

Aging

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“…6 Alterations of gene expression: to be included within diagnostic workflows RNA sequencing (RNAseq) technologies allow the quantitative and qualitative analysis of gene expression in different cells and tissues, enabling the reconstruction of the transcriptome, that is, the set of coding and noncoding transcripts. Among its potential applications, RNAseq can be of use in the diagnosis of rare genetic disorders to identify differentially expressed isoforms and alternative splicing, detect gene fusions and predict the functional impact of genetic variants (especially non-coding variants), increasing the diagnostic yield by up to 15% compared with WES alone (Peymani et al, 2022).…”

Section: Application Of Lrs To the Diagnosis Of Imprinting Disordersmentioning

confidence: 99%

Long read sequencing on its way to the routine diagnostics of genetic diseases

Olivucci,

Iovino,

Innella

et al. 2024

Front. Genet.

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The clinical application of technological progress in the identification of DNA alterations has always led to improvements of diagnostic yields in genetic medicine. At chromosome side, from cytogenetic techniques evaluating number and gross structural defects to genomic microarrays detecting cryptic copy number variants, and at molecular level, from Sanger method studying the nucleotide sequence of single genes to the high-throughput next-generation sequencing (NGS) technologies, resolution and sensitivity progressively increased expanding considerably the range of detectable DNA anomalies and alongside of Mendelian disorders with known genetic causes. However, particular genomic regions (i.e., repetitive and GC-rich sequences) are inefficiently analyzed by standard genetic tests, still relying on laborious, time-consuming and low-sensitive approaches (i.e., southern-blot for repeat expansion or long-PCR for genes with highly homologous pseudogenes), accounting for at least part of the patients with undiagnosed genetic disorders. Third generation sequencing, generating long reads with improved mappability, is more suitable for the detection of structural alterations and defects in hardly accessible genomic regions. Although recently implemented and not yet clinically available, long read sequencing (LRS) technologies have already shown their potential in genetic medicine research that might greatly impact on diagnostic yield and reporting times, through their translation to clinical settings. The main investigated LRS application concerns the identification of structural variants and repeat expansions, probably because techniques for their detection have not evolved as rapidly as those dedicated to single nucleotide variants (SNV) identification: gold standard analyses are karyotyping and microarrays for balanced and unbalanced chromosome rearrangements, respectively, and southern blot and repeat-primed PCR for the amplification and sizing of expanded alleles, impaired by limited resolution and sensitivity that have not been significantly improved by the advent of NGS. Nevertheless, more recently, with the increased accuracy provided by the latest product releases, LRS has been tested also for SNV detection, especially in genes with highly homologous pseudogenes and for haplotype reconstruction to assess the parental origin of alleles with de novo pathogenic variants. We provide a review of relevant recent scientific papers exploring LRS potential in the diagnosis of genetic diseases and its potential future applications in routine genetic testing.

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“…However, the underlying pathogenesis of BD remains elusive. With the rapid development of high-throughput sequencing technology and bioinformatics has significantly improved the diagnosis and treatment of diseases ( 4 ). However, there is a lack of sensitive and specific biomarkers that can be widely used in the clinical diagnosis of BD ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring hub genes and crucial pathways linked to oxidative stress in bipolar disorder depressive episodes through bioinformatics analysis

Wu,

Hu,

et al. 2024

Front. Psychiatry

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BackgroundBipolar disorder (BD) is a complex and serious psychiatric condition primarily characterized by bipolar depression, with the underlying genetic determinants yet to be elucidated. There is a substantial body of literature linking psychiatric disorders, including BD, to oxidative stress (OS). Consequently, this study aims to assess the relationship between BD and OS by identifying key hub genes implicated in OS pathways.MethodsWe acquired gene microarray data from GSE5392 through the Gene Expression Omnibus (GEO). Our approach encompassed differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Protein-Protein Interaction (PPI) Network analysis to pinpoint hub genes associated with BD. Subsequently, we utilized Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to identify hub genes relevant to OS. To evaluate the diagnostic accuracy of these hub genes, we performed receiver operating characteristic curve (ROC) analysis on both GSE5388 and GSE5389 datasets. Furthermore, we conducted a study involving ten BD patients and ten healthy controls (HCs) who met the special criteria, assessing the expression levels of these hub genes in their peripheral blood mononuclear cells (PBMCs).ResultsWe identified 411 down-regulated genes and 69 up-regulated genes for further scrutiny. Through WGCNA, we obtained 22 co-expression modules, with the sienna3 module displaying the strongest association with BD. By integrating differential analysis with genes linked to OS, we identified 44 common genes. Subsequent PPI Network and WGCNA analyses confirmed three hub genes as potential biomarkers for BD. Functional enrichment pathway analysis revealed their involvement in neuronal signal transduction, oxidative phosphorylation, and metabolic obstacle pathways. Using the Cytoscape plugin “ClueGo assay,” we determined that a majority of these targets regulate neuronal synaptic plasticity. ROC curve analysis underscored the excellent diagnostic value of these three hub genes. Quantitative reverse transcription-PCR (RT-qPCR) results indicated significant changes in the expression of these hub genes in the PBMCs of BD patients compared to HCs.ConclusionWe identified three hub genes (TAC1, MAP2K1, and MAP2K4) in BD associated with OS, potentially influencing the diagnosis and treatment of BD. Based on the GEO database, our study provides novel insights into the relationship between BD and OS, offering promising therapeutic targets.

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RNA sequencing role and application in clinical diagnostic

Cited by 15 publications

References 50 publications

ZCCHC12 promotes the progression of osteosarcoma via PI3K/AKT pathway

ZCCHC12 promotes the progression of osteosarcoma via PI3K/AKT pathway

Long read sequencing on its way to the routine diagnostics of genetic diseases

Exploring hub genes and crucial pathways linked to oxidative stress in bipolar disorder depressive episodes through bioinformatics analysis

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