{"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":null,"pages":null},"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":null,"pages":null},"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}
Current GenomicsPub Date : 2024-06-20DOI: 10.2174/0113892029300694240612081006
Qingqing Li, Yuxin Chu, Yi Yao, Qibin Song
{"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":null,"pages":null},"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":null,"pages":null},"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}
Current GenomicsPub Date : 2024-06-11DOI: 10.2174/0113892029300608240531111743
Zhiwei Peng, Can Fang, Zhiwei Tong, Qiufan Rao, Zihao Ren, K. Hu
{"title":"Crosstalk Between Cancer-associated Fibroblasts and Myeloid Cells\u0000Shapes the Heterogeneous Microenvironment of Gastric Cancer","authors":"Zhiwei Peng, Can Fang, Zhiwei Tong, Qiufan Rao, Zihao Ren, K. Hu","doi":"10.2174/0113892029300608240531111743","DOIUrl":"https://doi.org/10.2174/0113892029300608240531111743","url":null,"abstract":"\u0000\u0000Targeted therapies have improved the clinical outcomes of most patients\u0000with cancer. However, the heterogeneity of gastric cancer remains a major hurdle for precision\u0000treatment. Further investigations into tumor microenvironment heterogeneity are required to resolve\u0000these problems.\u0000\u0000\u0000\u0000In this study, bioinformatic analyses, including metabolism analysis, pathway enrichment,\u0000differentiation trajectory inference, regulatory network construction, and survival analysis,\u0000were applied to gain a comprehensive understanding of tumor microenvironment biology within\u0000gastric cancer using single-cell RNA-seq and public datasets and experiments were carried out to\u0000confirm the conclusions of these analyses.\u0000\u0000\u0000\u0000We profiled heterogeneous single-cell atlases and identified eight cell populations with\u0000differential expression patterns. We identified two cancer-associated fibroblasts (CAFs) subtypes,\u0000with particular emphasis on the role of inflammatory cancer-associated fibroblasts (iCAFs) in\u0000EMT and lipid metabolic crosstalk within the tumor microenvironment. Notably, we detected two\u0000differentiation states of iCAFs that existed in different tissues with discrepant expression of genes\u0000involved in immuno-inflammation or ECM remodeling. Moreover, investigation of tumor-infiltrating\u0000myeloid cells has revealed the functional diversity of myeloid cell lineages in gastric cancer.\u0000Of which a proliferative cell lineage named C1QC+MKI67+TAMs was recognized with high immunosuppressive\u0000capacities, suggesting it has immune suppression and cell proliferation functions\u0000in the tumor niche. Finally, we explored regulatory networks based on ligand-receptor pairs and\u0000found crucial pro-tumor crosstalk between CAFs and myeloid cells in the tumor microenvironment\u0000(TME).\u0000\u0000\u0000\u0000These findings provide insights for future cancer treatments and drug discovery\u0000","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141359640","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}