Current Genomics最新文献

{"title":"Pan-Genomics: Insight into the Functional Genome, Applications, Advancements, and Challenges","authors":"Akansha Sarwad, Spoorti Hosgoudar, Prachi Parvatikar","doi":"10.2174/0113892029311541240627111506","DOIUrl":"https://doi.org/10.2174/0113892029311541240627111506","url":null,"abstract":": A pan-genome is a compilation of the common and unique genomes found in a given species. It incorporates the genetic information from all of the genomes sampled, producing a big and diverse set of genetic material. Pan-genomic analysis has various advantages over typical genomics research. It creates a vast and varied spectrum of genetic material by combining the genetic data from all the sampled genomes. Comparing pan-genomics analysis to conventional genomic research, there are a number of benefits. Although the most recent era of pan-genomic studies has used cutting-edge sequencing technology to shed fresh light on biological variety and improvement, the potential uses of pan-genomics in improvement have not yet been fully realized. Pangenome research in various organisms has demonstrated that missing genetic components and the detection of significant Structural Variants (SVs) can be investigated using pan-genomic methods. Many individual-specific sequences have been linked to biological adaptability, phenotypic, and key economic attributes. This study aims to focus on how pangenome analysis uncovers genetic differences in various organisms, including human, and their effects on phenotypes, as well as how this might help us comprehend the diversity of species. The review also concentrated on potential problems and the prospects for future pangenome research.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"29 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141548802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene-Knockdown Methods for Silencing Nuclear-Localized Insulin Receptors in Lung Adenocarcinoma Cells: A Bioinformatics Approach","authors":"Qiu Ren, Hui Ma, Lingling Wang, Jiayu Qin, Miao Tian, Wei Zhang","doi":"10.2174/0113892029298721240627095839","DOIUrl":"https://doi.org/10.2174/0113892029298721240627095839","url":null,"abstract":"Background: Lung adenocarcinoma, the predominant subtype of lung cancer, presents a significant challenge to public health due to its notably low five-year survival rate. Recent epidemiological data highlights a concerning trend: patients with pulmonary adenocarcinoma and comorbid diabetes exhibit substantially elevated mortality rates compared to those without diabetes, suggesting a potential link between hyperinsulinemia in diabetic individuals and accelerated progression of pulmonary adenocarcinoma. Insulin Receptor (IR) is a tyrosine-protein kinase on the cell surface, and its over-expression is considered the pathological hallmark of hyperinsulinemia in various cancer cell types. Research indicates that IR can translocate to the nucleus of lung adenocarcinoma cells to promote their proliferation, but its precise molecular targets remain unclear. This study aims to silence IRs in lung adenocarcinoma cells and identify key genes within the ERK pathway that may serve as potential molecular targets for intervention. Methods: Gene expression data from lung adenocarcinoma and para cancer tissues were retrieved from the Gene Expression Omnibus (GEO) database and assessed through \"pheatmap\", GO annotation, KEGG analysis, R calculations, Cytoscape mapping, and Hub gene screening. Significant genes were visualized using the ggplot2 tool to compare expression patterns between the two groups. Additionally, survival analysis was performed using the R \"survminer\" and \"survival\" packages, along with the R \"pathview\" package for pathway visualization. Marker genes were identified and linked to relevant signaling pathways. Validation was conducted utilizing real-time quantitative polymerase chain reaction and immunoblotting assays in an A549 lung cancer cell model to determine the roles of these marker genes in associated signaling cascades. Results: The study examined 58 lung adenocarcinoma samples and paired para-neoplastic tissues. Analysis of the GSE32863 dataset from GEO revealed 1040 differentially expressed genes, with 421 up-regulated and 619 down-regulated. Visualization of these differences identified 172 significant alterations, comprising 141 up-regulated and 31 down-regulated genes. Functional enrichment analysis using Gene Ontology (GO) revealed 56 molecular functions, 77 cellular components, and 816 biological processes. KEGG analysis identified 17 strongly enriched functions, including cytokine interactions and tumor necrosis factor signaling. Moreover, the ERK signaling pathway was associated with four Hub genes (FGFR4, ANGPT1, TEK, and IL1B) in cellular biological processes. Further validation demonstrated a positive correlation between IL-1B expression in the ERK signaling pathway and lung cancer through real-time fluorescence quantitative enzyme- linked reaction with immunoblotting assays. Conclusion: In IR-silenced lung adenocarcinoma, the expression of the IL-1B gene exhibited a positive correlation with the ERK signaling pathway.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"21 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141548803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAT4 Mutation is Related to Tumor Mutation Burden and Favorable Prognosis in Gastric Cancer","authors":"Qingqing Li, Yuxin Chu, Yi Yao, Qibin Song","doi":"10.2174/0113892029300694240612081006","DOIUrl":"https://doi.org/10.2174/0113892029300694240612081006","url":null,"abstract":"Objective: This study aimed to investigate the frequently mutated genes in Gastric Cancer (GC), assess their association with Tumor Mutation Burden (TMB) and the patients’ survival, and identify the potential biomarkers for tailored therapy. Methods: Simple somatic mutation data of GC were collected from the TCGA and ICGC databases. The high-frequency mutated genes were identified from both datasets. The samples were initially dichotomized into wild-type and mutation groups based on the status of overlapping genes. TMB difference between the two groups was evaluated by the Mann-Whitney U-test. Survival difference between the two groups was compared by the Kaplan-Meier method with a log-rank test. The prognostic value of the target gene was assessed by the Cox proportional hazards model. The signaling pathways involved in FAT4 mutation were identified by Gene Set Enrichment Analysis (GSEA). The fractions of different tumor-infiltrating immune cells were calculated by the CIBERSORT algorithm. Results: 21 overlapping genes with frequent mutation were identified in both datasets. Mutation of these genes was significantly associated with higher TMB (P<0.05) in GC. The survival of the FAT4 mutation group was superior to the wild-type group. FAT4 mutation was also identified as an independent favorable prognostic factor for the GC patients. GSEA indicated that FAT4 mutation activated the signaling pathways involved in energy metabolism. Finally, CD4 memory-activated T cells, follicular helper T cells, and gamma delta T cells were significantly more enriched, while naïve B cells and regulatory T cells (Tregs) were significantly less enriched in the FAT4 mutation group (P<0.05). Conclusion: FAT4 mutation is relevant to TMB and favorable prognosis in GC, which may become a useful biomarker for immunotherapy of GC patients.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"18 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141509539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Multi-Omic Approaches to the Molecular Diagnosis of Mitochondrial Disease and Available Strategies for Treatment and Prevention","authors":"Faeze Khagani, Mahboube Hemmati, Masoumeh Ebrahimi, Arash Salmaninejad","doi":"10.2174/0113892029308327240612110334","DOIUrl":"https://doi.org/10.2174/0113892029308327240612110334","url":null,"abstract":": Mitochondria are semi-autonomous organelles present in several copies within most cells in the human body that are controlled by the precise collaboration of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) encoding mitochondrial proteins. They play important roles in numerous metabolic pathways, such as the synthesis of adenosine triphosphate (ATP), the predominant energy substrate of the cell generated through oxidative phosphorylation (OXPHOS), intracellular calcium homeostasis, metabolite biosynthesis, aging, cell cycles, and so forth. Previous studies revealed that dysfunction of these multi-functional organelles, which may arise due to mutations in either the nuclear or mitochondrial genome, leads to a diverse group of clinically and genetically heterogeneous disorders. These diseases include neurodegenerative and metabolic disorders as well as cardiac and skeletal myopathies in both adults and newborns. The plethora of phenotypes and defects displayed leads to challenges in the diagnosis and treatment of mitochondrial diseases. In this regard, the related literature proposed several diagnostic options, such as high throughput mitochondrial genomics and omics technologies, as well as numerous therapeutic options, such as pharmacological approaches, manipulating the mitochondrial genome, increasing the mitochondria content of the affected cells, and recently mitochondrial diseases transmission prevention. Therefore, the present article attempted to review the latest advances and challenges in diagnostic and therapeutic options for mitochondrial diseases.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"171 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141530070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the Genetic Complexity of Classical Hodgkin Lymphoma: Insights and Effective Strategies","authors":"Chaeyoung Lee, Yeeun An","doi":"10.2174/0113892029301904240513045755","DOIUrl":"https://doi.org/10.2174/0113892029301904240513045755","url":null,"abstract":": Understanding the genetics of susceptibility to classical Hodgkin lymphoma (cHL) is considerably limited compared to other cancers due to the rare Hodgkin and Reed-Sternberg (HRS) tumor cells, which coexist with the predominant non-malignant microenvironment. This article offers insights into genetic abnormalities in cHL, as well as nucleotide variants and their associated target genes, elucidated through recent technological advancements. Oncogenomes in HRS cells highlight the survival and proliferation of these cells through hyperactive signaling in specific pathways (e.g., NF-kB) and their interplay with microenvironmental cells (e.g., CD4+ T cells). In contrast, the susceptibility genes identified from genome-wide association studies and expression quantitative trait locus analyses only vaguely implicate their potential roles in susceptibility to more general cancers. To pave the way for the era of precision oncology, more intensive efforts are imperative, employing the following strategies: exploring genetic heterogeneity by gender and cHL subtype, investigating colocalization with various types of expression quantitative trait loci, and leveraging single-cell analysis. These approaches provide valuable perspectives for unraveling the genetic complexities of cHL.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"48 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141168800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HPV16 Genomes: In Silico Analysis of E6 and E7 Oncoproteins in 20 South American Variants","authors":"Márcio Fabrício Falcão de Paula Filho, Lara Luisa Lopes Chrisóstomo, Isaac Farias Cansanção","doi":"10.2174/0113892029293113240427065916","DOIUrl":"https://doi.org/10.2174/0113892029293113240427065916","url":null,"abstract":"Background: Human papillomavirus (HPV) is the main risk factor for the development of squamous cell cervical cancer, and E6 oncoprotein and E7 oncoprotein are important components of the viral genome and its oncogenic potential. It is known that different viral variants of HPV16 have different pathology and impact on the development of neoplasia, although few studies have been performed on South American variants. Objective: Therefore, the present study aimed to analyze in silico the genomic diversity of HPV16 in 20 complete genome variants of South America in the National Center for Biotechnology Information (NCBI) database. Methods: We performed a descriptive study to characterize the polymorphic regions of the E6 and E7 genes in HPV16 variants, using software for genomic data and single nucleotide polymorphism (SNP) analysis and others for phylogenetic analysis. Results: The variants analyzed included six SNPs linked to cancer (A131G, G145T, C335T, T350G, C712A, and T732C) and significant variation (798 nucleotide substitutions). Despite this, the variants showed low genetic diversity. Eighteen variants of unclear significance (VUS) were identified, 10 of which were in the coding E6 regions and 8 in the coding E7 regions. The prevalence of lineage D variants is of concern due to their pathology in cervical cancer and requires more research and epidemiological vigilance regarding their prevalence in the population. Conclusion: study may contribute to future research on South American variants of HPV16, their pathogenicity, and the development of treatments.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"15 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140931828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global and Local Ancestry and its Importance: A Mini-Review","authors":"Rangasai Chandra Goli, Kiyevi G. Chishi, Indrajit Ganguly, Sanjeev Singh, S.P. Dixit, Pallavi Rathi, Vikas Diwakar, Chandana Sree C, Omkar Maharudra Limbalkar, Nidhi Sukhija, K.K. Kanaka","doi":"10.2174/0113892029298909240426094055","DOIUrl":"https://doi.org/10.2174/0113892029298909240426094055","url":null,"abstract":": The fastest way to significantly change the composition of a population is through admixture, an evolutionary mechanism. In animal breeding history, genetic admixture has provided both short-term and long-term advantages by utilizing the phenomenon of complementarity and heterosis in several traits and genetic diversity, respectively. The traditional method of admixture analysis by pedigree records has now been replaced greatly by genome-wide marker data that enables more precise estimations. Among these markers, SNPs have been the popular choice since they are cost-effective, not so laborious, and automation of genotyping is easy. Certain markers can suggest the possibility of a population's origin from a sample of DNA where the source individual is unknown or unwilling to disclose their lineage, which are called Ancestry-Informative Markers (AIMs). Revealing admixture level at the locus-specific level is termed as local ancestry and can be exploited to identify signs of recent selective response and can account for genetic drift. Considering the importance of genetic admixture and local ancestry, in this mini-review, both concepts are illustrated, encompassing basics, their estimation/identification methods, tools/- software used and their applications.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"61 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140931827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Analysis of Clinical Outcome of Mesenchymal Stem Cellrelated Genes in Pan-cancer","authors":"Mingzhe Jiang, Dantong Zhu, Dong Zhao, Yongye Liu, Jia Li, Zhendong Zheng","doi":"10.2174/0113892029291247240422060811","DOIUrl":"https://doi.org/10.2174/0113892029291247240422060811","url":null,"abstract":"Background: Although the application of mesenchymal stem cells (MSCs) in engineered medicine, such as tissue regeneration, is well known, new evidence is emerging that shows that MSCs can also promote cancer progression, metastasis, and drug resistance. However, no large-scale cohort analysis of MSCs has been conducted to reveal their impact on the prognosis of cancer patients. Objective: We propose the MSC score as a novel surrogate for poor prognosis in pan-cancer Methods: We used single sample gene set enrichment analysis to quantify MSC-related genes into a signature score and identify the signature score as a potential independent prognostic marker for cancer using multivariate Cox regression analysis. TIDE algorithm and neural network were utilized to assess the predictive accuracy of MSC-related genes for immunotherapy. Results: MSC-related gene expression significantly differed between normal and tumor samples across the 33 cancer types. Cox regression analysis suggested the MSC score as an independent prognostic marker for kidney renal papillary cell carcinoma, mesothelioma, glioma, and stomach adenocarcinoma. The abundance of fibroblasts was also more representative of the MSC score than the stromal score. Our findings supported the combined use of the TIDE algorithm and neural network to predict the accuracy of MSC-related genes for immunotherapy. Conclusion: We comprehensively characterized the transcriptome, genome, and epigenetics of MSCs in pan-cancer and revealed the crosstalk of MSCs in the tumor microenvironment, especially with cancer-related fibroblasts. It is suggested that this may be one of the key sources of resistance to cancer immunotherapy.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"76 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140811924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection and Quantification of 5moU RNA Modification from Direct RNA Sequencing Data","authors":"Jiayi Li, Feiyang Sun, Kunyang He, Lin Zhang, Jia Meng, Daiyun Huang, Yuxin Zhang","doi":"10.2174/0113892029288843240402042529","DOIUrl":"https://doi.org/10.2174/0113892029288843240402042529","url":null,"abstract":"Background: Chemically modified therapeutic mRNAs have gained momentum recently. In addition to commonly used modifications (e.g., pseudouridine), 5moU is considered a promising substitution for uridine in therapeutic mRNAs. Accurate identification of 5-methoxyuridine (5moU) would be crucial for the study and quality control of relevant in vitro-transcribed (IVT) mRNAs. However, current methods exhibit deficiencies in providing quantitative methodologies for detecting such modification. Utilizing the capabilities of Oxford nanopore direct RNA sequencing, in this study, we present NanoML-5moU, a machine-learning framework designed specifically for the read-level detection and quantification of 5moU modification for IVT data. Method: Nanopore direct RNA sequencing data from both 5moU-modified and unmodified control samples were collected. Subsequently, a comprehensive analysis and modeling of signal event characteristics (mean, median current intensities, standard deviations, and dwell times) were performed. Furthermore, classical machine learning algorithms, notably the Support Vector Machine (SVM), Random Forest (RF), and XGBoost were employed to discern 5moU modifications within NNUNN (where N represents A, C, U, or G) 5-mers. Result: Notably, the signal event attributes pertaining to each constituent base of the NNUNN 5-mers, in conjunction with the utilization of the XGBoost algorithm, exhibited remarkable performance levels (with a maximum AUROC of 0.9567 in the \"AGTTC\" reference 5-mer dataset and a minimum AUROC of 0.8113 in the \"TGTGC\" reference 5-mer dataset). This accomplishment markedly exceeded the efficacy of the prevailing background error comparison model (ELIGOs AUC 0.751 for site-level prediction). The model's performance was further validated through a series of curated datasets, which featured customized modification ratios designed to emulate broader data patterns, demonstrating its general applicability in quality control of IVT mRNA vaccines. The NanoML-5moU framework is publicly available on GitHub (https://github.com/JiayiLi21/Nano ML-5moU). Conclusion: NanoML-5moU enables accurate read-level profiling of 5moU modification with nanopore direct RNA-sequencing, which is a powerful tool specialized in unveiling signal patterns in in vitro-transcribed (IVT) mRNAs.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"27 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140615001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ramifications of m6A Modification on ncRNAs in Cancer","authors":"Rashid Mehmood","doi":"10.2174/0113892029296712240405053201","DOIUrl":"https://doi.org/10.2174/0113892029296712240405053201","url":null,"abstract":":: N6-methyladenosine (m6A) is an RNA modification wherein the N6-position of adenosine is methylated. It is one of the most prevalent internal modifications of RNA and regulates various aspects of RNA metabolism. M6A is deposited by m6A methyltransferases, removed by m6A demethylases, and recognized by reader proteins, which modulate splicing, export, translation, and stability of the modified mRNA. Recent evidence suggests that various classes of non-- coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long con-coding RNAs (lncRNAs), are also targeted by this modification. Depending on the ncRNA species, m6A may affect the processing, stability, or localization of these molecules. The m6A-- modified ncRNAs are implicated in a number of diseases, including cancer. In this review, the author summarizes the role of m6A modification in the regulation and functions of ncRNAs in tumor development. Moreover, the potential applications in cancer prognosis and therapeutics are discussed.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"4 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140574312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}