Pub Date : 2024-02-21DOI: 10.2174/0113892029268176240125055419
Aditi R. Durge, Deepti D. Shrimankar
Problem: Analyzing genomic sequences plays a crucial role in understanding biological diversity and classifying Bamboo species. Existing methods for genomic sequence analysis suffer from limitations such as complexity, low accuracy, and the need for constant reconfiguration in response to evolving genomic datasets. Aim: This study addresses these limitations by introducing a novel Dual Heuristic Feature Selection- based Ensemble Classification Model (DHFS-ECM) for the precise identification of Bamboo species from genomic sequences. Methods: The proposed DHFS-ECM method employs a Genetic Algorithm to perform dual heuristic feature selection. This process maximizes inter-class variance, leading to the selection of informative N-gram feature sets. Subsequently, intra-class variance levels are used to create optimal training and validation sets, ensuring comprehensive coverage of class-specific features. The selected features are then processed through an ensemble classification layer, combining multiple stratification models for species-specific categorization. Results: Comparative analysis with state-of-the-art methods demonstrate that DHFS-ECM achieves remarkable improvements in accuracy (9.5%), precision (5.9%), recall (8.5%), and AUC performance (4.5%). Importantly, the model maintains its performance even with an increased number of species classes due to the continuous learning facilitated by the Dual Heuristic Genetic Algorithm Model. Conclusion: DHFS-ECM offers several key advantages, including efficient feature extraction, reduced model complexity, enhanced interpretability, and increased robustness and accuracy through the ensemble classification layer. These attributes make DHFS-ECM a promising tool for real-time clinical applications and a valuable contribution to the field of genomic sequence analysis.
{"title":"DHFS-ECM: Design of a Dual Heuristic Feature Selection-based Ensemble Classification Model for the Identification of Bamboo Species from Genomic Sequences","authors":"Aditi R. Durge, Deepti D. Shrimankar","doi":"10.2174/0113892029268176240125055419","DOIUrl":"https://doi.org/10.2174/0113892029268176240125055419","url":null,"abstract":"Problem: Analyzing genomic sequences plays a crucial role in understanding biological diversity and classifying Bamboo species. Existing methods for genomic sequence analysis suffer from limitations such as complexity, low accuracy, and the need for constant reconfiguration in response to evolving genomic datasets. Aim: This study addresses these limitations by introducing a novel Dual Heuristic Feature Selection- based Ensemble Classification Model (DHFS-ECM) for the precise identification of Bamboo species from genomic sequences. Methods: The proposed DHFS-ECM method employs a Genetic Algorithm to perform dual heuristic feature selection. This process maximizes inter-class variance, leading to the selection of informative N-gram feature sets. Subsequently, intra-class variance levels are used to create optimal training and validation sets, ensuring comprehensive coverage of class-specific features. The selected features are then processed through an ensemble classification layer, combining multiple stratification models for species-specific categorization. Results: Comparative analysis with state-of-the-art methods demonstrate that DHFS-ECM achieves remarkable improvements in accuracy (9.5%), precision (5.9%), recall (8.5%), and AUC performance (4.5%). Importantly, the model maintains its performance even with an increased number of species classes due to the continuous learning facilitated by the Dual Heuristic Genetic Algorithm Model. Conclusion: DHFS-ECM offers several key advantages, including efficient feature extraction, reduced model complexity, enhanced interpretability, and increased robustness and accuracy through the ensemble classification layer. These attributes make DHFS-ECM a promising tool for real-time clinical applications and a valuable contribution to the field of genomic sequence analysis.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139951511","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: Pakistan has a high burden of oral cancers, with a prevalence rate of around 9%. Oral Squamous Cell Carcinoma (OSCC) accounts for about 90% of oral cancer cases. Epithelial to Mesenchymal Transition (EMT) gets highly stimulated in tumor cells by adopting subsequent malignant features of highly invasive cancer populations. Zinc Finger E-Box binding factors, ZEB1 and ZEB2, are regulatory proteins that promote EMT by suppressing the adherent ability of cells transforming into highly motile cancerous cells. The present study aimed to analyze the expression of EMT regulators, ZEB1 and ZEB2, and their association with the clinicopathological features in different grades of OSCC patients. Methods: Tissue samples were collected for both case and control groups from the recruited study participants. Cancer tissues (cases) were collected from the confirmed OSCC patients, and healthy tissues (controls) were collected from third-molar dental extraction patients. The study participants were recruited with informed consent and brief demographic and clinical characteristics. The case group was further segregated with respect to the histological cancer grading system into well-differentiated (WD), moderately differentiated (MD), and poorly differentiated (PD) squamous cell carcinoma (SCC) groups. RNA was extracted from the tissue samples for expression profiling of ZEB1 and ZEB2 genes through quantitative real-time PCR (qRT-PCR) Results: All of the recruited participants had a mean age of 46.55 ± 11.7 (years), with most of them belonging to Urdu speaking ethnic group and were married. The BMI (kg/m2 ) of the healthy participants was in the normal range (18-22 kg/m2 ). However, BMI was found to be reduced with the proliferation in the pathological state of cancer. The oral hygiene of patients was better than the healthy participants, possibly due to the strict oral hygiene practice concerns of consultants. Every recruited OSCC patient had one or multiple addiction habits for more than a year. Patients reported health frailty (46.6%), unhealed mouth sores (40%), swallowing difficulties and white/reddish marks (80%), and restricted mouth opening (64.4%). Furthermore, 82.2% of the recruited patients observed symptoms within 1-12 months, and buccal mucosa was the most exposed tumor site among 55.6% of the patients. Expression profiling of EMT regulators showed gradual over-expressions of ZEB1 (8, 20, and 42 folds) and ZEB2 (4, 10, and 18 folds) in respective histological cancer grades. Conclusion: High expressions of ZEBs have been significantly associated with cancer progression and poor health. However, no association was found between OSCC with other clinicopathological features when compared to healthy controls
{"title":"Expression Profiling of EMT Transcriptional Regulators ZEB1 and ZEB2 in Different Histopathological Grades of Oral Squamous Cell Carcinoma Patients","authors":"Neha Baqai, Rafat Amin, Tehseen Fatima, Zeba Ahmed, Nousheen Faiz","doi":"10.2174/0113892029284920240212091903","DOIUrl":"https://doi.org/10.2174/0113892029284920240212091903","url":null,"abstract":"Background: Pakistan has a high burden of oral cancers, with a prevalence rate of around 9%. Oral Squamous Cell Carcinoma (OSCC) accounts for about 90% of oral cancer cases. Epithelial to Mesenchymal Transition (EMT) gets highly stimulated in tumor cells by adopting subsequent malignant features of highly invasive cancer populations. Zinc Finger E-Box binding factors, ZEB1 and ZEB2, are regulatory proteins that promote EMT by suppressing the adherent ability of cells transforming into highly motile cancerous cells. The present study aimed to analyze the expression of EMT regulators, ZEB1 and ZEB2, and their association with the clinicopathological features in different grades of OSCC patients. Methods: Tissue samples were collected for both case and control groups from the recruited study participants. Cancer tissues (cases) were collected from the confirmed OSCC patients, and healthy tissues (controls) were collected from third-molar dental extraction patients. The study participants were recruited with informed consent and brief demographic and clinical characteristics. The case group was further segregated with respect to the histological cancer grading system into well-differentiated (WD), moderately differentiated (MD), and poorly differentiated (PD) squamous cell carcinoma (SCC) groups. RNA was extracted from the tissue samples for expression profiling of ZEB1 and ZEB2 genes through quantitative real-time PCR (qRT-PCR) Results: All of the recruited participants had a mean age of 46.55 ± 11.7 (years), with most of them belonging to Urdu speaking ethnic group and were married. The BMI (kg/m2 ) of the healthy participants was in the normal range (18-22 kg/m2 ). However, BMI was found to be reduced with the proliferation in the pathological state of cancer. The oral hygiene of patients was better than the healthy participants, possibly due to the strict oral hygiene practice concerns of consultants. Every recruited OSCC patient had one or multiple addiction habits for more than a year. Patients reported health frailty (46.6%), unhealed mouth sores (40%), swallowing difficulties and white/reddish marks (80%), and restricted mouth opening (64.4%). Furthermore, 82.2% of the recruited patients observed symptoms within 1-12 months, and buccal mucosa was the most exposed tumor site among 55.6% of the patients. Expression profiling of EMT regulators showed gradual over-expressions of ZEB1 (8, 20, and 42 folds) and ZEB2 (4, 10, and 18 folds) in respective histological cancer grades. Conclusion: High expressions of ZEBs have been significantly associated with cancer progression and poor health. However, no association was found between OSCC with other clinicopathological features when compared to healthy controls","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139751828","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}
: SARS-CoV-2 is a highly contagious and transmissible viral infection that first emerged in 2019 and since then has sparked an epidemic of severe respiratory problems identified as “coronavirus disease 2019” (COVID-19) that causes a hazard to human life and safety. The virus developed mainly from bats. The current epidemic has presented a significant warning to life across the world by showing mutation. There are different tests available for testing Coronavirus, and RTPCR is the best, giving more accurate results, but it is also time-consuming. There are different options available for treating n-CoV-19, which include medications such as Remdesivir, corticosteroids, plasma therapy, Dexamethasone therapy, etc. The development of vaccines such as BNT126b2, ChAdOX1, mRNA-1273 and BBIBP-CorV has provided great relief in dealing with the virus as they decreased the mortality rate. BNT126b2 and ChAdOX1 are two n-CoV vaccines found to be most effective in controlling the spread of infection. In the future, nanotechnology-based vaccines and immune engineering techniques can be helpful for further research on Coronavirus and treatment of this deadly virus. The existing knowledge about the existence of SARS-- CoV-2, along with its variants, is summarized in this review. This review, based on recently published findings, presents the core genetics of COVID-19, including heritable characteristics, pathogenesis, immunological biomarkers, treatment options and clinical updates on the virus, along with patents.
{"title":"COVID-19: Recent Insight in Genomic Feature, Pathogenesis, Immunological Biomarkers, Treatment Options and Clinical Updates on SARS-CoV-2","authors":"Rohitas Deshmukh, Ranjit K Harwansh, Akash Garg, Sakshi Mishra, Rutvi Agrawal, Rajendra Jangde","doi":"10.2174/0113892029291098240129113500","DOIUrl":"https://doi.org/10.2174/0113892029291098240129113500","url":null,"abstract":": SARS-CoV-2 is a highly contagious and transmissible viral infection that first emerged in 2019 and since then has sparked an epidemic of severe respiratory problems identified as “coronavirus disease 2019” (COVID-19) that causes a hazard to human life and safety. The virus developed mainly from bats. The current epidemic has presented a significant warning to life across the world by showing mutation. There are different tests available for testing Coronavirus, and RTPCR is the best, giving more accurate results, but it is also time-consuming. There are different options available for treating n-CoV-19, which include medications such as Remdesivir, corticosteroids, plasma therapy, Dexamethasone therapy, etc. The development of vaccines such as BNT126b2, ChAdOX1, mRNA-1273 and BBIBP-CorV has provided great relief in dealing with the virus as they decreased the mortality rate. BNT126b2 and ChAdOX1 are two n-CoV vaccines found to be most effective in controlling the spread of infection. In the future, nanotechnology-based vaccines and immune engineering techniques can be helpful for further research on Coronavirus and treatment of this deadly virus. The existing knowledge about the existence of SARS-- CoV-2, along with its variants, is summarized in this review. This review, based on recently published findings, presents the core genetics of COVID-19, including heritable characteristics, pathogenesis, immunological biomarkers, treatment options and clinical updates on the virus, along with patents.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139751750","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 : 2024-01-29DOI: 10.2174/0113892029278082240118053857
Aiyan Xing, Dongxiao Lv, Changshun Wu, Kai Zhou, Tianhui Zhao, Lihua Zhao, Huaqing Wang, Hong Feng
Objectives: This study aims to assess the prognostic implications of gene signature of the tertiary lymphoid structures (TLSs) in head and neck squamous cell carcinoma (HNSCC) and scrutinize the influence of TLS on immune infiltration. Methods: Patients with HNSCC from the Cancer Genome Atlas were categorized into high/low TLS signature groups based on the predetermined TLS signature threshold. The association of the TLS signature with the immune microenvironment, driver gene mutation status, and tumor mutational load was systematically analyzed. Validation was conducted using independent datasets (GSE41613 and GSE102349). Results: Patients with a high TLS signature score exhibited better prognosis compared to those with a low TLS signature score. The group with a high TLS signature score had significantly higher immune cell subpopulations compared to the group with a low TLS signature score. Moreover, the major immune cell subpopulations and immune circulation characteristics in the tumor immune microenvironment were positively correlated with the TLS signature. Mutational differences in driver genes were observed between the TLS signature high/low groups, primarily in the cell cycle and NRF2 signaling pathways. Patients with TP53 mutations and high TLS signature scores demonstrated a better prognosis compared to those with TP53 wild-type. In the independent cohort, the relationship between TLS signatures and patient prognosis and immune infiltration was also confirmed. Additionally, immune-related biological processes and signaling pathways were activated with elevated TLS signature. Conclusion: High TLS signature is a promising independent prognostic factor for HNSCC patients. Immunological analysis indicated a correlation between TLS and immune cell infiltration in HNSCC. These findings provide a theoretical basis for future applications of TLS signature in HNSCC prognosis and immunotherapy.
{"title":"Tertiary Lymphoid Structures Gene Signature Predicts Prognosis and Immune Infiltration Analysis in Head and Neck Squamous Cell Carcinoma","authors":"Aiyan Xing, Dongxiao Lv, Changshun Wu, Kai Zhou, Tianhui Zhao, Lihua Zhao, Huaqing Wang, Hong Feng","doi":"10.2174/0113892029278082240118053857","DOIUrl":"https://doi.org/10.2174/0113892029278082240118053857","url":null,"abstract":"Objectives: This study aims to assess the prognostic implications of gene signature of the tertiary lymphoid structures (TLSs) in head and neck squamous cell carcinoma (HNSCC) and scrutinize the influence of TLS on immune infiltration. Methods: Patients with HNSCC from the Cancer Genome Atlas were categorized into high/low TLS signature groups based on the predetermined TLS signature threshold. The association of the TLS signature with the immune microenvironment, driver gene mutation status, and tumor mutational load was systematically analyzed. Validation was conducted using independent datasets (GSE41613 and GSE102349). Results: Patients with a high TLS signature score exhibited better prognosis compared to those with a low TLS signature score. The group with a high TLS signature score had significantly higher immune cell subpopulations compared to the group with a low TLS signature score. Moreover, the major immune cell subpopulations and immune circulation characteristics in the tumor immune microenvironment were positively correlated with the TLS signature. Mutational differences in driver genes were observed between the TLS signature high/low groups, primarily in the cell cycle and NRF2 signaling pathways. Patients with TP53 mutations and high TLS signature scores demonstrated a better prognosis compared to those with TP53 wild-type. In the independent cohort, the relationship between TLS signatures and patient prognosis and immune infiltration was also confirmed. Additionally, immune-related biological processes and signaling pathways were activated with elevated TLS signature. Conclusion: High TLS signature is a promising independent prognostic factor for HNSCC patients. Immunological analysis indicated a correlation between TLS and immune cell infiltration in HNSCC. These findings provide a theoretical basis for future applications of TLS signature in HNSCC prognosis and immunotherapy.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584907","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}
Objective:: Specific methylation sites have shown promise in the early diagnosis of lung adenocarcinoma (LUAD). However, their utility in predicting LUAD prognosis remains unclear. This study aimed to construct a reliable methylation-based predictor for accurately predicting the prognosis of LUAD patients. Method:: DNA methylation data and survival data from LUAD patients were obtained from the TCGA and a GEO series. A DNA methylation-based signature was developed using univariate least absolute shrinkage and selection operators and multivariate Cox regression models. Result:: Eight CpG sites were identified and validated as optimal prognostic signatures for the overall survival of LUAD patients. Receiver operating characteristic analysis demonstrated the high predictive ability of the eight-site methylation signature combined with clinical factors for overall survival. Conclusion:: This research successfully identified a novel eight-site methylation signature for predicting the overall survival of LUAD patients through bioinformatic integrated analysis of gene methylation markers used in the early diagnosis of lung cancer.
{"title":"A Novel Methylation-Based Model for Prognostic Prediction in Lung Adenocarcinoma","authors":"Manyuan Li, Xufeng Deng, Dong Zhou, Xiaoqing Liu, Jigang Dai, Quanxing Liu","doi":"10.2174/0113892029277397231228062412","DOIUrl":"https://doi.org/10.2174/0113892029277397231228062412","url":null,"abstract":"Objective:: Specific methylation sites have shown promise in the early diagnosis of lung adenocarcinoma (LUAD). However, their utility in predicting LUAD prognosis remains unclear. This study aimed to construct a reliable methylation-based predictor for accurately predicting the prognosis of LUAD patients. Method:: DNA methylation data and survival data from LUAD patients were obtained from the TCGA and a GEO series. A DNA methylation-based signature was developed using univariate least absolute shrinkage and selection operators and multivariate Cox regression models. Result:: Eight CpG sites were identified and validated as optimal prognostic signatures for the overall survival of LUAD patients. Receiver operating characteristic analysis demonstrated the high predictive ability of the eight-site methylation signature combined with clinical factors for overall survival. Conclusion:: This research successfully identified a novel eight-site methylation signature for predicting the overall survival of LUAD patients through bioinformatic integrated analysis of gene methylation markers used in the early diagnosis of lung cancer.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139557725","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: 10.2174/0113892029273682240111052317
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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}
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