Pub Date : 2024-01-23DOI: 10.2174/0113892029273682240111052317
Mu Runhong, Chang Mingzhu, Feng Chuanbo, Cui Yunhe, Li Tingyu, Liu Chang, Wang Yilin, Guo Xiao
Objective:: This research aimed to study the expression of PRDX6 mRNA in hepatocellular carcinoma (HCC) and its effect on the prognosis of HCC. Moreover, the effect of PRDX6 gene knockdown on the proliferation, migration, and invasion of HepG2 cells mediated by lentivirus was also examined. This study offers a theoretical and experimental basis for further research on the mechanism of PRDX6 in liver cancer and new methods for clinical diagnosis and treatment. Methods:: RNA sequence data of 369 HCC patients were screened through the TCGA database, and the expression and clinical characteristics of PRDX6 mRNA were analyzed based on high- -throughput RNA sequencing data. HepG2 cells were divided into WT, sh-NC and sh-PRDX6 groups. Real-time PCR and Western blot were used to detect the expression levels of the PRDX6 gene and protein, respectively. CCK8 method was used to detect the proliferation activity of Hep- G2 cells, scratch healing test was used to detect the migration ability, Transwell chamber was used to detect the invasion ability, and Western blot was used to detect the expression levels of PI3K/Akt/mTOR signaling pathway and Notch signaling pathway-related proteins. Results:: The expression of PRDX6 was significantly correlated with the gender, race, clinical stage, histological grade, and survival time of HCC patients (P < 0.05). Compared with that in WT and sh-NC groups, the expression level of PRDX6 protein in HCC patients was significantly lower (P < 0.01), the proliferation activity of HCC cells was significantly decreased (P < 0.05), and the migration and invasion ability was significantly decreased (P <0.05) in the sh-PRDX6 group. The expression levels of PI3K, p-Akt, p-mTOR, Notch1, and Hes1 proteins in the sh- PRDX6 group were significantly lower than those in WT and sh-NC groups (P < 0.05). Conclusion:: The expression of PRDX6 may be closely related to the prognosis of HCC. Lentivirus- mediated PRDX6 knockdown can inhibit the proliferation, migration and invasion of HCC cells, which may be related to its regulating the PI3K/Akt/mTOR and Notch1 signaling pathways. PRDX6 is expected to be a new target for the diagnosis and treatment of liver cancer.
{"title":"Analysis of the Expression of PRDX6 in Patients with Hepatocellular Carcinoma and its Effect on the Phenotype of Hepatocellular Carcinoma Cells","authors":"Mu Runhong, Chang Mingzhu, Feng Chuanbo, Cui Yunhe, Li Tingyu, Liu Chang, Wang Yilin, Guo Xiao","doi":"10.2174/0113892029273682240111052317","DOIUrl":"https://doi.org/10.2174/0113892029273682240111052317","url":null,"abstract":"Objective:: This research aimed to study the expression of PRDX6 mRNA in hepatocellular carcinoma (HCC) and its effect on the prognosis of HCC. Moreover, the effect of PRDX6 gene knockdown on the proliferation, migration, and invasion of HepG2 cells mediated by lentivirus was also examined. This study offers a theoretical and experimental basis for further research on the mechanism of PRDX6 in liver cancer and new methods for clinical diagnosis and treatment. Methods:: RNA sequence data of 369 HCC patients were screened through the TCGA database, and the expression and clinical characteristics of PRDX6 mRNA were analyzed based on high- -throughput RNA sequencing data. HepG2 cells were divided into WT, sh-NC and sh-PRDX6 groups. Real-time PCR and Western blot were used to detect the expression levels of the PRDX6 gene and protein, respectively. CCK8 method was used to detect the proliferation activity of Hep- G2 cells, scratch healing test was used to detect the migration ability, Transwell chamber was used to detect the invasion ability, and Western blot was used to detect the expression levels of PI3K/Akt/mTOR signaling pathway and Notch signaling pathway-related proteins. Results:: The expression of PRDX6 was significantly correlated with the gender, race, clinical stage, histological grade, and survival time of HCC patients (P < 0.05). Compared with that in WT and sh-NC groups, the expression level of PRDX6 protein in HCC patients was significantly lower (P < 0.01), the proliferation activity of HCC cells was significantly decreased (P < 0.05), and the migration and invasion ability was significantly decreased (P <0.05) in the sh-PRDX6 group. The expression levels of PI3K, p-Akt, p-mTOR, Notch1, and Hes1 proteins in the sh- PRDX6 group were significantly lower than those in WT and sh-NC groups (P < 0.05). Conclusion:: The expression of PRDX6 may be closely related to the prognosis of HCC. Lentivirus- mediated PRDX6 knockdown can inhibit the proliferation, migration and invasion of HCC cells, which may be related to its regulating the PI3K/Akt/mTOR and Notch1 signaling pathways. PRDX6 is expected to be a new target for the diagnosis and treatment of liver cancer.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"77 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139557548","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}
Pub Date : 2024-01-23DOI: 10.2174/0113892029285310231227105503
K Chandrashekar, Vidya Niranjan, Anagha S Setlur, Dhanya Pradeep, Jitendra Kumar
Introduction:: Colorectal cancers are the world’s third most commonly diagnosed type of cancer. Currently, there are several diagnostic and treatment options to combat it. However, a delay in detection of the disease is life-threatening. Additionally, a thorough analysis of the exomes of cancers reveals potential variation data that can be used for early disease prognosis. Method:: By utilizing a comprehensive computational investigation, the present study aimed to reveal mutations that could potentially predispose to colorectal cancer. Ten colorectal cancer exomes were retrieved. Quality control assessments were performed using FastQC and MultiQC, gapped alignment to the human reference genome (hg19) using Bowtie2 and calling the germline variants using Haplotype caller in the GATK pipeline. The variants were filtered and annotated using SIFT and PolyPhen2 successfully categorized the mutations into synonymous, non-synonymous, start loss and stop gain mutations as well as marked them as possibly damaging, probably damaging and benign. This mutational profile helped in shortlisting frequently occurring mutations and associated genes, for which the downstream multi-dimensional expression analyses were carried out. Result:: Our work involved prioritizing the non-synonymous, deleterious SNPs since these polymorphisms bring about a functional alteration to the phenotype. The top variations associated with their genes with the highest frequency of occurrence included LGALS8, CTSB, RAD17, CPNE1, OPRM1, SEMA4D, MUC4, PDE4DIP, ELN and ADRA1A. An in-depth multi-dimensional downstream analysis of all these genes in terms of gene expression profiling and analysis and differential gene expression with regard to various cancer types revealed CTSB and CPNE1 as highly expressed and overregulated genes in colorectal cancer. Conclusion:: Our work provides insights into the various alterations that might possibly lead to colorectal cancer and suggests the possibility of utilizing the most important genes identified for wetlab experimentation.
{"title":"Exploring the Role of Non-synonymous and Deleterious Variants Identified in Colorectal Cancer: A Multi-dimensional Computational Scrutiny of Exomes","authors":"K Chandrashekar, Vidya Niranjan, Anagha S Setlur, Dhanya Pradeep, Jitendra Kumar","doi":"10.2174/0113892029285310231227105503","DOIUrl":"https://doi.org/10.2174/0113892029285310231227105503","url":null,"abstract":"Introduction:: Colorectal cancers are the world’s third most commonly diagnosed type of cancer. Currently, there are several diagnostic and treatment options to combat it. However, a delay in detection of the disease is life-threatening. Additionally, a thorough analysis of the exomes of cancers reveals potential variation data that can be used for early disease prognosis. Method:: By utilizing a comprehensive computational investigation, the present study aimed to reveal mutations that could potentially predispose to colorectal cancer. Ten colorectal cancer exomes were retrieved. Quality control assessments were performed using FastQC and MultiQC, gapped alignment to the human reference genome (hg19) using Bowtie2 and calling the germline variants using Haplotype caller in the GATK pipeline. The variants were filtered and annotated using SIFT and PolyPhen2 successfully categorized the mutations into synonymous, non-synonymous, start loss and stop gain mutations as well as marked them as possibly damaging, probably damaging and benign. This mutational profile helped in shortlisting frequently occurring mutations and associated genes, for which the downstream multi-dimensional expression analyses were carried out. Result:: Our work involved prioritizing the non-synonymous, deleterious SNPs since these polymorphisms bring about a functional alteration to the phenotype. The top variations associated with their genes with the highest frequency of occurrence included LGALS8, CTSB, RAD17, CPNE1, OPRM1, SEMA4D, MUC4, PDE4DIP, ELN and ADRA1A. An in-depth multi-dimensional downstream analysis of all these genes in terms of gene expression profiling and analysis and differential gene expression with regard to various cancer types revealed CTSB and CPNE1 as highly expressed and overregulated genes in colorectal cancer. Conclusion:: Our work provides insights into the various alterations that might possibly lead to colorectal cancer and suggests the possibility of utilizing the most important genes identified for wetlab experimentation.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"123 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139557741","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}
Pub Date : 2024-01-23DOI: 10.2174/0113892029279786240111052824
Tannu Bhagchandani, Mohd Maksuf Ul Haque, Shilpa Sharma, Md Zubbair Malik, Ashwini Kumar Ray, Urvinder S. Kaur, Ankita Rai, Anjali Verma, Kamal Kumar Sawlani, Rupesh Chaturvedi, D Himanshu, Abhishek Kumar, Ravi Tandon
Background:: The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment of immunocompromised (CD4 count <200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. Objective:: We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Methods:: Plasma viral DNA from PWH on ART and controls were used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. Results:: In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Conclusion:: Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.
背景血浆病毒组代表了血浆中病毒序列的整体组成。有报道称，在治疗免疫力低下（CD4 细胞数为 200）的艾滋病病毒感染者（PWH）时，血浆病毒组会发生改变。然而，人们对接受抗逆转录病毒疗法（ART）治疗且 CD4 细胞数保持不变的艾滋病病毒感染者病毒组组成的影响知之甚少。目的我们旨在评估与 HIV 阴性未感染对照组相比，接受抗逆转录病毒疗法的 PWH 血浆病毒组的变化，并进一步研究血浆病毒与炎症和免疫功能障碍（即免疫衰老和免疫衰竭）之间可能存在的关联。研究方法使用 Illumina Nextseq500 平台对接受抗逆转录病毒疗法的 PWH 和对照组的血浆病毒 DNA 进行测序，然后使用 VIROMATCH 自动流水线鉴定病毒序列。多重细胞因子检测用于测量血浆中各种细胞因子的浓度。对 PBMC 进行免疫分型，以确定免疫衰老和免疫衰竭的 T 细胞标记物。结果在我们的观察性横断面试点研究中，与对照组相比，接受抗逆转录病毒疗法的慢性感染 PWH 的病毒种类组成明显不同。PWH的血浆病毒组显示，人类γ疱疹病毒4（又称爱泼斯坦-巴尔病毒（EBV））的相对丰度明显较高。此外，在接受抗逆转录病毒疗法的 PWH 中，EBV 是一个重要的病毒分类群，它与接受抗逆转录病毒疗法的 PWH 的 T 细胞衰竭表型和 TNF-α 的显著增加呈正相关。此外，在接受抗逆转录病毒疗法的 PWH 中还检测到衰老 T 细胞和 IL-8 细胞因子的比例明显增加。结论血浆病毒组的改变影响了接受抗逆转录病毒疗法的 PWH 的炎症反应和 T 细胞表型。
{"title":"Plasma Virome of HIV-infected Subjects on Suppressive Antiretroviral Therapy Reveals Association of Differentially Abundant Viruses with Distinct T-cell Phenotypes and Inflammation","authors":"Tannu Bhagchandani, Mohd Maksuf Ul Haque, Shilpa Sharma, Md Zubbair Malik, Ashwini Kumar Ray, Urvinder S. Kaur, Ankita Rai, Anjali Verma, Kamal Kumar Sawlani, Rupesh Chaturvedi, D Himanshu, Abhishek Kumar, Ravi Tandon","doi":"10.2174/0113892029279786240111052824","DOIUrl":"https://doi.org/10.2174/0113892029279786240111052824","url":null,"abstract":"Background:: The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment of immunocompromised (CD4 count <200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. Objective:: We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Methods:: Plasma viral DNA from PWH on ART and controls were used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. Results:: In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Conclusion:: Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"8 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139557744","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}
Pub Date : 2024-01-21DOI: 10.2174/0113892029272497240103052359
Badr A Alsayed, Rashid Mir, Mohammad Muzaffar Mir, Tarig M.S. Alnour, Shereen Fawzy, M. Ahmed Mesaik, Dnyanesh Amle
Background: Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. Methods: The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Results: Frequencies of TNF-α rs1800629 GA and AA, IL-8 rs4073 TA and AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA and GA+AA genotypes and the A allele, IL-8 rs4073 TA and AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. Conclusion: The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.
{"title":"Molecular Determination of Tumor Necrosis Factor-alpha, Interleukin-8, Interleukin-10, and C-X-C Chemokine Receptor-2 Genetic Variations and their Association with Disease Susceptibility and Mortality in COVID-19 Patients","authors":"Badr A Alsayed, Rashid Mir, Mohammad Muzaffar Mir, Tarig M.S. Alnour, Shereen Fawzy, M. Ahmed Mesaik, Dnyanesh Amle","doi":"10.2174/0113892029272497240103052359","DOIUrl":"https://doi.org/10.2174/0113892029272497240103052359","url":null,"abstract":"Background: Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. Methods: The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Results: Frequencies of TNF-α rs1800629 GA and AA, IL-8 rs4073 TA and AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA and GA+AA genotypes and the A allele, IL-8 rs4073 TA and AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. Conclusion: The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"201 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139518127","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}
Pub Date : 2024-01-10DOI: 10.2174/0113892029283759231227075715
Max Garzon, Fredy Alexander Colorado
This article draws a perspective on the increasingly unavoidable question of whether steps can be taken in genomics and biology at large to move them more rapidly towards more analytical and deductive biology, akin to similar developments that occurred in other natural sciences, such as physics and chemistry, centuries ago. It provides a summary of recent advances in other relevant sciences in the last 3 decades that are likely to pull it in that direction in the next decade or so, as well as what methods and tools will make it possible.
{"title":"Towards an Analytical Biology","authors":"Max Garzon, Fredy Alexander Colorado","doi":"10.2174/0113892029283759231227075715","DOIUrl":"https://doi.org/10.2174/0113892029283759231227075715","url":null,"abstract":"\u0000\u0000This article draws a perspective on the increasingly unavoidable question of whether\u0000steps can be taken in genomics and biology at large to move them more rapidly towards more analytical\u0000and deductive biology, akin to similar developments that occurred in other natural sciences,\u0000such as physics and chemistry, centuries ago. It provides a summary of recent advances in other\u0000relevant sciences in the last 3 decades that are likely to pull it in that direction in the next decade\u0000or so, as well as what methods and tools will make it possible.\u0000","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"69 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139440844","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}
Pub Date : 2023-12-08DOI: 10.2174/0113892029276542231205065843
Ayushi Gupta, Suresh Nair
Background:: The brown planthopper (BPH) is a monophagous sap-sucking insect pest of rice that is responsible for massive yield loss. BPH populations, even when genetically homogenous, can display a vast range of phenotypes, and the development of effective pest-management strategies requires a good understanding of what generates this phenotypic variation. One potential source could be epigenetic differences. Methods:: With this premise, we explored epigenetic diversity, structure and differentiation in field populations of BPH collected across the rice-growing seasons over a period of two consecutive years. Using a modified methylation-sensitive restriction assay (MSRA) and CpG island amplification- representational difference analysis, site-specific cytosine methylation of five stress-responsive genes (CYP6AY1, CYP6ER1, Carboxylesterase, Endoglucanase, Tf2-transposon) was estimated, for identifying methylation-based epiallelic markers and epigenetic variation across BPH populations. Results:: Using a cost-effective and rapid protocol, our study, for the first time, revealed the epigenetic component of phenotypic variations in the wild populations of BPH. Besides, results showed that morphologically indistinguishable populations of BPH can be epigenetically distinct. Conclusion:: Screening field-collected BPH populations revealed the presence of previously unreported epigenetic polymorphisms and provided a platform for future studies aimed at investigating their significance for BPH. Furthermore, these findings can form the basis for understanding the contribution(s) of DNA methylation in providing phenotypic plasticity to BPH.
背景：：褐飞虱（BPH）是水稻的一种单食性吸汁害虫，是造成大量减产的原因。即使在基因同源的情况下，褐飞虱种群也会表现出各种各样的表型，要想制定有效的害虫管理策略，就必须充分了解是什么导致了这种表型变异。表观遗传差异可能是其中一个潜在来源。方法：：在此前提下，我们探索了连续两年在水稻生长季节收集的 BPH 田间种群的表观遗传多样性、结构和分化。利用改良的甲基化敏感限制分析法（MSRA）和CpG岛扩增-代表性差异分析法，估算了五个应激反应基因（CYP6AY1、CYP6ER1、羧酸酯酶、内切葡聚糖酶、Tf2-转座子）的特异性胞嘧啶甲基化位点，以确定基于甲基化的外显子标记和BPH种群间的表观遗传变异。结果我们的研究采用了一种经济有效的快速方法，首次揭示了 BPH 野生种群表型变异的表观遗传因素。此外，研究结果表明，在形态上难以区分的 BPH 种群在表观遗传学上可能是不同的。结论筛选野外采集的牛肝菌种群发现了以前未报道过的表观遗传多态性，为今后研究这些多态性对牛肝菌的意义提供了一个平台。此外，这些发现可为了解 DNA 甲基化在提供良性前列腺增生症表型可塑性方面的作用奠定基础。
{"title":"Epigenetic Diversity Underlying Seasonal and Annual Variations in Brown Planthopper (BPH) Populations as Revealed by Methylationsensitive Restriction Assay","authors":"Ayushi Gupta, Suresh Nair","doi":"10.2174/0113892029276542231205065843","DOIUrl":"https://doi.org/10.2174/0113892029276542231205065843","url":null,"abstract":"Background:: The brown planthopper (BPH) is a monophagous sap-sucking insect pest of rice that is responsible for massive yield loss. BPH populations, even when genetically homogenous, can display a vast range of phenotypes, and the development of effective pest-management strategies requires a good understanding of what generates this phenotypic variation. One potential source could be epigenetic differences. Methods:: With this premise, we explored epigenetic diversity, structure and differentiation in field populations of BPH collected across the rice-growing seasons over a period of two consecutive years. Using a modified methylation-sensitive restriction assay (MSRA) and CpG island amplification- representational difference analysis, site-specific cytosine methylation of five stress-responsive genes (CYP6AY1, CYP6ER1, Carboxylesterase, Endoglucanase, Tf2-transposon) was estimated, for identifying methylation-based epiallelic markers and epigenetic variation across BPH populations. Results:: Using a cost-effective and rapid protocol, our study, for the first time, revealed the epigenetic component of phenotypic variations in the wild populations of BPH. Besides, results showed that morphologically indistinguishable populations of BPH can be epigenetically distinct. Conclusion:: Screening field-collected BPH populations revealed the presence of previously unreported epigenetic polymorphisms and provided a platform for future studies aimed at investigating their significance for BPH. Furthermore, these findings can form the basis for understanding the contribution(s) of DNA methylation in providing phenotypic plasticity to BPH.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"94 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138563305","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}
Pub Date : 2023-12-01DOI: 10.2174/0113892029286632231127055733
Mariya Levkova, Trifon Chervenkov, Lyudmila Angelova, Deyan Dzenkov
: Advanced medical technologies are transforming the future of healthcare, in particular, the screening and detection of molecular-genetic changes in patients suspected of having a neoplasm. They are based on the assumption that neoplasms release small amounts of various neoplasm- specific molecules, such as tumor DNA, called circulating DNA (cirDNA), into the extracellular space and subsequently into the blood. The detection of tumor-specific molecules and specific molecular changes in body fluids in a noninvasive or minimally invasive approach is known as “liquid biopsy.” The aim of this review is to summarize the current knowledge of the application of ONT for analyzing circulating DNA in the field of liquid biopsies among cancer patients. Databases were searched using the keywords “nanopore” and “liquid biopsy” and by applying strict inclusion criteria. This technique can be used for the detection of neoplastic disease, including metastases, guiding precision therapy, and monitoring its effects. There are many challenges, however, for the successful implementation of this technology into the clinical practice. The first one is the low amount of tumor-specific molecules in the body fluids. Secondly, a tumor molecular signature should be discriminated from benign conditions like clonal hematopoiesis of unknown significance. Oxford Nanopore Technology (ONT) is a third-generation sequencing technology that seems particularly promising to complete these tasks. It offers rapid sequencing thanks to its ability to detect changes in the density of the electric current passing through nanopores. Even though ONT still needs validation technology, it is a promising approach for early diagnosis, therapy guidance, and monitoring of different neoplasms based on analyzing the cirDNA.
{"title":"Oxford Nanopore Technology and its Application in Liquid Biopsies","authors":"Mariya Levkova, Trifon Chervenkov, Lyudmila Angelova, Deyan Dzenkov","doi":"10.2174/0113892029286632231127055733","DOIUrl":"https://doi.org/10.2174/0113892029286632231127055733","url":null,"abstract":": Advanced medical technologies are transforming the future of healthcare, in particular, the screening and detection of molecular-genetic changes in patients suspected of having a neoplasm. They are based on the assumption that neoplasms release small amounts of various neoplasm- specific molecules, such as tumor DNA, called circulating DNA (cirDNA), into the extracellular space and subsequently into the blood. The detection of tumor-specific molecules and specific molecular changes in body fluids in a noninvasive or minimally invasive approach is known as “liquid biopsy.” The aim of this review is to summarize the current knowledge of the application of ONT for analyzing circulating DNA in the field of liquid biopsies among cancer patients. Databases were searched using the keywords “nanopore” and “liquid biopsy” and by applying strict inclusion criteria. This technique can be used for the detection of neoplastic disease, including metastases, guiding precision therapy, and monitoring its effects. There are many challenges, however, for the successful implementation of this technology into the clinical practice. The first one is the low amount of tumor-specific molecules in the body fluids. Secondly, a tumor molecular signature should be discriminated from benign conditions like clonal hematopoiesis of unknown significance. Oxford Nanopore Technology (ONT) is a third-generation sequencing technology that seems particularly promising to complete these tasks. It offers rapid sequencing thanks to its ability to detect changes in the density of the electric current passing through nanopores. Even though ONT still needs validation technology, it is a promising approach for early diagnosis, therapy guidance, and monitoring of different neoplasms based on analyzing the cirDNA.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"91 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138524432","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}
Background: The ATM gene encodes a multifunctional kinase involved in important cellular functions, such as checkpoint signaling and apoptosis, in response to DNA damage. Bi-allelic pathogenic variants in this gene cause Ataxia Telangiectasia (AT), while carriers of ATM pathogenic variants are at increased risk of cancer depending on the pathogenicity of the variant they carry. Identifying pathogenic variants can aid in the management of the disease in carriers. Methods: Whole-exome sequencing (WES) was performed on three unrelated patients from the Iranian-Azeri Turkish ethnic group referred to a genetic center for analysis. WES was also conducted on 400 individuals from the same ethnic group to determine the frequencies of all ATM variants. Blood samples were collected from the patients and their family members for DNA extraction, and PCR-Sanger sequencing was performed to confirm the WES results. Results: The first proband with AT disease had two novel compound heterozygote variants (c.2639-2A>T, c.8708delC) in the ATM gene revealed by WES analysis, which was potentially/- likely pathogenic. The second proband with bi-lateral breast cancer had a homozygous pathogenic variant (c.6067G>A) in the ATM gene identified by WES analysis. The third case with a family history of cancer had a heterozygous synonymous pathogenic variant (c.7788G>A) in the ATM gene found by WES analysis. Sanger sequencing confirmed the WES results, and bioinformatics analysis of the mutated ATM RNA and protein structure added evidence for the potential pathogenicity of the novel variants. WES analysis of the cohort revealed 38 different variants, including a variant (rs1800057, ATM:c.3161C>G, p.P1054R) associated with prostate cancer that had a higher frequency in our cohort. Conclusion: Genetic analysis of three unrelated families with ATM-related disorders discovered two novel pathogenic variants. A homozygous missense pathogenic variant was identified in a woman with bi-lateral breast cancer, and a pathogenic synonymous pathogenic variant was found in a family with a history of different cancers.
{"title":"Identification of Two Novel Pathogenic Variants of the ATM Gene in the Iranian-Azeri Turkish Ethnic Group by Applying Whole Exome Sequencing","authors":"Amir-Reza Dalal Amandi, Neda Jabbarpour, Shadi Shiva, Mortaza Bonyadi","doi":"10.2174/0113892029268949231104165301","DOIUrl":"https://doi.org/10.2174/0113892029268949231104165301","url":null,"abstract":"Background: The ATM gene encodes a multifunctional kinase involved in important cellular functions, such as checkpoint signaling and apoptosis, in response to DNA damage. Bi-allelic pathogenic variants in this gene cause Ataxia Telangiectasia (AT), while carriers of ATM pathogenic variants are at increased risk of cancer depending on the pathogenicity of the variant they carry. Identifying pathogenic variants can aid in the management of the disease in carriers. Methods: Whole-exome sequencing (WES) was performed on three unrelated patients from the Iranian-Azeri Turkish ethnic group referred to a genetic center for analysis. WES was also conducted on 400 individuals from the same ethnic group to determine the frequencies of all ATM variants. Blood samples were collected from the patients and their family members for DNA extraction, and PCR-Sanger sequencing was performed to confirm the WES results. Results: The first proband with AT disease had two novel compound heterozygote variants (c.2639-2A>T, c.8708delC) in the ATM gene revealed by WES analysis, which was potentially/- likely pathogenic. The second proband with bi-lateral breast cancer had a homozygous pathogenic variant (c.6067G>A) in the ATM gene identified by WES analysis. The third case with a family history of cancer had a heterozygous synonymous pathogenic variant (c.7788G>A) in the ATM gene found by WES analysis. Sanger sequencing confirmed the WES results, and bioinformatics analysis of the mutated ATM RNA and protein structure added evidence for the potential pathogenicity of the novel variants. WES analysis of the cohort revealed 38 different variants, including a variant (rs1800057, ATM:c.3161C>G, p.P1054R) associated with prostate cancer that had a higher frequency in our cohort. Conclusion: Genetic analysis of three unrelated families with ATM-related disorders discovered two novel pathogenic variants. A homozygous missense pathogenic variant was identified in a woman with bi-lateral breast cancer, and a pathogenic synonymous pathogenic variant was found in a family with a history of different cancers.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"1 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138524457","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}
Pub Date : 2023-11-29DOI: 10.2174/0113892029269523231101051455
Sony K. Ahuja, Deepti D. Shrimankar, Aditi R. Durge
: Human gene sequences are considered a primary source of comprehensive information about different body conditions. A wide variety of diseases including cancer, heart issues, brain issues, genetic issues, etc. can be pre-empted via efficient analysis of genomic sequences. Researchers have proposed different configurations of machine learning models for processing genomic sequences, and each of these models varies in terms of their performance & applicability characteristics. Models that use bioinspired optimizations are generally slower, but have superior incrementalperformance, while models that use one-shot learning achieve higher instantaneous accuracy but cannot be scaled for larger disease-sets. Due to such variations, it is difficult for genomic system designers to identify optimum models for their application-specific & performance-specific use cases. To overcome this issue, a detailed survey of different genomic processing models in terms of their functional nuances, application-specific advantages, deployment-specific limitations, and contextual future scopes is discussed in this text. Based on this discussion, researchers will be able to identify optimal models for their functional use cases. This text also compares the reviewed models in terms of their quantitative parameter sets, which include, the accuracy of classification, delay needed to classify large-length sequences, precision levels, scalability levels, and deployment cost, which will assist readers in selecting deployment-specific models for their contextual clinical scenarios. This text also evaluates a novel Genome Processing Efficiency Rank (GPER) for each of these models, which will allow readers to identify models with higher performance and low overheads under real-time scenarios.
{"title":"A Study and Analysis of Disease Identification using Genomic Sequence Processing Models: An Empirical Review","authors":"Sony K. Ahuja, Deepti D. Shrimankar, Aditi R. Durge","doi":"10.2174/0113892029269523231101051455","DOIUrl":"https://doi.org/10.2174/0113892029269523231101051455","url":null,"abstract":": Human gene sequences are considered a primary source of comprehensive information about different body conditions. A wide variety of diseases including cancer, heart issues, brain issues, genetic issues, etc. can be pre-empted via efficient analysis of genomic sequences. Researchers have proposed different configurations of machine learning models for processing genomic sequences, and each of these models varies in terms of their performance & applicability characteristics. Models that use bioinspired optimizations are generally slower, but have superior incrementalperformance, while models that use one-shot learning achieve higher instantaneous accuracy but cannot be scaled for larger disease-sets. Due to such variations, it is difficult for genomic system designers to identify optimum models for their application-specific & performance-specific use cases. To overcome this issue, a detailed survey of different genomic processing models in terms of their functional nuances, application-specific advantages, deployment-specific limitations, and contextual future scopes is discussed in this text. Based on this discussion, researchers will be able to identify optimal models for their functional use cases. This text also compares the reviewed models in terms of their quantitative parameter sets, which include, the accuracy of classification, delay needed to classify large-length sequences, precision levels, scalability levels, and deployment cost, which will assist readers in selecting deployment-specific models for their contextual clinical scenarios. This text also evaluates a novel Genome Processing Efficiency Rank (GPER) for each of these models, which will allow readers to identify models with higher performance and low overheads under real-time scenarios.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":"29 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138524431","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}
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