Genomics & informatics最新文献_第6页

Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach. 抗结核分枝杆菌耐药菌株的多表位疫苗：全蛋白质组减影和免疫信息学方法。

Genomics & informatics Pub Date : 2023-09-01 Epub Date: 2023-09-27 DOI: 10.5808/gi.23021

Md Tahsin Khan, Araf Mahmud, Md Muzahidul Islam, Mst Sayedatun Nessa Sumaia, Zeaur Rahim, Kamrul Islam, Asif Iqbal

{"title":"Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach.","authors":"Md Tahsin Khan, Araf Mahmud, Md Muzahidul Islam, Mst Sayedatun Nessa Sumaia, Zeaur Rahim, Kamrul Islam, Asif Iqbal","doi":"10.5808/gi.23021","DOIUrl":"10.5808/gi.23021","url":null,"abstract":"Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Toll-like receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"21 3","pages":"e42"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Whole genomic sequencing of Staphylococcus aureus strain RMI-014804 isolated from pulmonary patient sputum via next-generation sequencing technology. 通过下一代测序技术对从肺部患者痰液中分离的金黄色葡萄球菌菌株RMI-014804进行全基因组测序。

Genomics & informatics Pub Date : 2023-09-01 Epub Date: 2023-09-27 DOI: 10.5808/gi.23024

Ayesha Wisal, Asad Ullah, Waheed Anwar, Carlos M Morel, Syed Shah Hassan

{"title":"Whole genomic sequencing of Staphylococcus aureus strain RMI-014804 isolated from pulmonary patient sputum via next-generation sequencing technology.","authors":"Ayesha Wisal, Asad Ullah, Waheed Anwar, Carlos M Morel, Syed Shah Hassan","doi":"10.5808/gi.23024","DOIUrl":"10.5808/gi.23024","url":null,"abstract":"Nosocomial infections, commonly referred to as healthcare-associated infections, are illnesses that patients get while hospitalized and are typically either not yet manifest or may develop. One of the most prevalent nosocomial diseases in hospitalized patients is pneumonia, among the leading causes of mortality and morbidity. Viral, bacterial, and fungal pathogens cause pneumonia. More severe introductions commonly included Staphylococcus aureus, which is at the top of bacterial infections, per World Health Organization reports. The staphylococci, S. aureus, strain RMI-014804, mesophile, on-sporulating, and non-motile bacterium, was isolated from the sputum of a pulmonary patient in Pakistan. Many characteristics of S. aureus strain RMI-014804 have been revealed in this paper, with complete genome sequence and annotation. Our findings indicate that the genome is a single circular 2.82 Mbp long genome with 1,962 protein-coding genes, 15 rRNA, 49 tRNA, 62 pseudogenes, and a GC content of 28.76%. As a result of this genome sequencing analysis, researchers will fully understand the genetic and molecular basis of the virulence of the S. aureus bacteria, which could help prevent the spread of nosocomial infections like pneumonia. Genome analysis of this strain was necessary to identify the specific genes and molecular mechanisms that contribute to its pathogenicity, antibiotic resistance, and genetic diversity, allowing for a more in-depth investigation of its pathogenesis to develop new treatments and preventive measures against infections caused by this bacterium.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"21 3","pages":"e34"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association of CAPN10 gene (rs3842570) polymorphism with the type 2 diabetes mellitus among the population of Noakhali region in Bangladesh: a case-control study. 孟加拉国Noakhali地区人群CAPN10基因（rs3842570）多态性与2型糖尿病的相关性：一项病例对照研究。

Genomics & informatics Pub Date : 2023-09-01 Epub Date: 2023-09-27 DOI: 10.5808/gi.23023

Munia Sultana, Md Mafizul Islam, Md Murad Hossain, Md Anisur Rahman, Shuvo Chandra Das, Dhirendra Nath Barman, Farhana Siddiqi Mitu, Shipan Das Gupta

{"title":"Association of CAPN10 gene (rs3842570) polymorphism with the type 2 diabetes mellitus among the population of Noakhali region in Bangladesh: a case-control study.","authors":"Munia Sultana, Md Mafizul Islam, Md Murad Hossain, Md Anisur Rahman, Shuvo Chandra Das, Dhirendra Nath Barman, Farhana Siddiqi Mitu, Shipan Das Gupta","doi":"10.5808/gi.23023","DOIUrl":"10.5808/gi.23023","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) is a multifactorial, polygenic, and metabolically complicated disease. A large number of genes are responsible for the biogenesis of T2DM and calpain10 (CAPN10) is one of them. The association of numerous CAPN10 genetic polymorphisms in the development of T2DM has been widely studied in different populations and noticed inconclusive results. The present study is an attempt to evaluate the plausible association of CAPN10 polymorphism SNP-19 (rs3842570) with T2DM and T2DM-related anthropometric and metabolic traits in the Noakhali region of Bangladesh. This case-control study included 202 T2DM patients and 75 healthy individuals from different places in Noakhali. A significant association (p < 0.05) of SNP-19 with T2DM in co-dominant 2R/3R vs. 3R/3R (odds ratio [OR], 2.7; p=0.0014) and dominant (2R/3R) + (2R/2R) vs. 3R/3R (OR, 2.47; p=0.0011) genetic models was observed. High-risk allele 2R also showed a significant association with T2DM in the allelic model (OR, 1.67; p=0.0109). The genotypic frequency of SNP-19 variants showed consistency with Hardy-Weinberg equilibrium (p > 0.05). Additionally, SNP-19 genetic variants showed potential associations with the anthropometric and metabolic traits of T2DM patients in terms of body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, and triglycerides. Our approach identifies the 2R/3R genotype of SNP-19 as a significant risk factor for biogenesis of T2DM in the Noakhali population. Furthermore, a large-scale study could be instrumental to correlate this finding in overall Bangladeshi population.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"21 3","pages":"e33"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of druggable genes for multiple myeloma based on genomic information. 基于基因组信息的多发性骨髓瘤药物基因鉴定。

Genomics & informatics Pub Date : 2023-09-01 Epub Date: 2023-09-27 DOI: 10.5808/gi.23011

Rahmat Dani Satria, Lalu Muhammad Irham, Wirawan Adikusuma, Anisa Nova Puspitaningrum, Arief Rahman Afief, Riat El Khair, Abdi Wira Septama

{"title":"Identification of druggable genes for multiple myeloma based on genomic information.","authors":"Rahmat Dani Satria, Lalu Muhammad Irham, Wirawan Adikusuma, Anisa Nova Puspitaningrum, Arief Rahman Afief, Riat El Khair, Abdi Wira Septama","doi":"10.5808/gi.23011","DOIUrl":"10.5808/gi.23011","url":null,"abstract":"Multiple myeloma (MM) is a hematological malignancy. It is widely believed that genetic factors play a significant role in the development of MM, as investigated in numerous studies. However, the application of genomic information for clinical purposes, including diagnostic and prognostic biomarkers, remains largely confined to research. In this study, we utilized genetic information from the Genomic-Driven Clinical Implementation for Multiple Myeloma database, which is dedicated to clinical trial studies on MM. This genetic information was sourced from the genome-wide association studies catalog database. We prioritized genes with the potential to cause MM based on established annotations, as well as biological risk genes for MM, as potential drug target candidates. The DrugBank database was employed to identify drug candidates targeting these genes. Our research led to the discovery of 14 MM biological risk genes and the identification of 10 drugs that target three of these genes. Notably, only one of these 10 drugs, panobinostat, has been approved for use in MM. The two most promising genes, calcium signal-modulating cyclophilin ligand (CAMLG) and histone deacetylase 2 (HDAC2), were targeted by four drugs (cyclosporine, belinostat, vorinostat, and romidepsin), all of which have clinical evidence supporting their use in the treatment of MM. Interestingly, five of the 10 drugs have been approved for other indications than MM, but they may also be effective in treating MM. Therefore, this study aimed to clarify the genomic variants involved in the pathogenesis of MM and highlight the potential benefits of these genomic variants in drug discovery.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"21 3","pages":"e31"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A streamlined pipeline based on HmmUFOtu for microbial community profiling using 16S rRNA amplicon sequencing. 使用16S rRNA扩增子测序进行微生物群落分析的基于HmUFOtu的精简管道。

Genomics & informatics Pub Date : 2023-09-01 Epub Date: 2023-07-31 DOI: 10.5808/gi.23044

Hyeonwoo Kim, Jiwon Kim, Ji Won Choi, Kwang-Sung Ahn, Dong-Il Park, Sangsoo Kim

{"title":"A streamlined pipeline based on HmmUFOtu for microbial community profiling using 16S rRNA amplicon sequencing.","authors":"Hyeonwoo Kim, Jiwon Kim, Ji Won Choi, Kwang-Sung Ahn, Dong-Il Park, Sangsoo Kim","doi":"10.5808/gi.23044","DOIUrl":"10.5808/gi.23044","url":null,"abstract":"Microbial community profiling using 16S rRNA amplicon sequencing allows for taxonomic characterization of diverse microorganisms. While amplicon sequence variant (ASV) methods are increasingly favored for their fine-grained resolution of sequence variants, they often discard substantial portions of sequencing reads during quality control, particularly in datasets with large number samples. We present a streamlined pipeline that integrates FastP for read trimming, HmmUFOtu for operational taxonomic units (OTU) clustering, Vsearch for chimera checking, and Kraken2 for taxonomic assignment. To assess the pipeline's performance, we reprocessed two published stool datasets of normal Korean populations: one with 890 and the other with 1,462 independent samples. In the first dataset, HmmUFOtu retained 93.2% of over 104 million read pairs after quality trimming, discarding chimeric or unclassifiable reads, while DADA2, a commonly used ASV method, retained only 44.6% of the reads. Nonetheless, both methods yielded qualitatively similar β-diversity plots. For the second dataset, HmmUFOtu retained 89.2% of read pairs, while DADA2 retained a mere 18.4% of the reads. HmmUFOtu, being a closed-reference clustering method, facilitates merging separately processed datasets, with shared OTUs between the two datasets exhibiting a correlation coefficient of 0.92 in total abundance (log scale). While the first two dimensions of the β-diversity plot exhibited a cohesive mixture of the two datasets, the third dimension revealed the presence of a batch effect. Our comparative evaluation of ASV and OTU methods within this streamlined pipeline provides valuable insights into their performance when processing large-scale microbial 16S rRNA amplicon sequencing data. The strengths of HmmUFOtu and its potential for dataset merging are highlighted.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"21 3","pages":"e40"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lack of association between the VEGFA gene polymorphisms and preterm birth in Korean women. 韩国妇女VEGFA基因多态性与早产之间缺乏相关性。

Genomics & informatics Pub Date : 2023-09-01 Epub Date: 2023-09-27 DOI: 10.5808/gi.22064

Yue Shi, Hyung Jun Kim, Seong Yong Kim, Ga Eun Kim, Han Jun Jin

{"title":"Lack of association between the VEGFA gene polymorphisms and preterm birth in Korean women.","authors":"Yue Shi, Hyung Jun Kim, Seong Yong Kim, Ga Eun Kim, Han Jun Jin","doi":"10.5808/gi.22064","DOIUrl":"10.5808/gi.22064","url":null,"abstract":"Preterm birth (PTB), a pregnancy-related disease, is defined as a birth before 37 weeks of gestation. It is a major cause of maternal mortality and morbidity worldwide, and its incidence rate is steadily increasing. Various genetic factors can contribute to the etiology of PTB. Vascular endothelial growth factor A (VEGFA) gene is an important angiogenic gene and its polymorphisms have been reported to be associated with PTB development. Therefore, we conducted a case-control study to evaluate the association between VEGFA rs699947, rs2010963, and rs3025039 polymorphisms and PTB in Korean women. A total of 271 subjects (116 patients with PTB and 155 women at ≥38 weeks of gestation) were analyzed in this study. The genotyping of VEGFA gene polymorphisms was performed using polymerase chain reaction- restriction fragment length polymorphism. No significant association between the patients with PTB and the control groups was confirmed. In the combination analysis, we found a significant association between PTB and VEGFA rs699947 CC-rs2010963 GG-rs3025039 CC combination (odds ratio, 3.77; 95% confidence interval, 1.091 to 13.032; p = 0.031). The VEGFA rs699947, rs2010963, and rs3025039 polymorphisms might have no genetic association with the pathogenesis of PTB in Korean women. However, the combination analysis indicates the possibility that VEGFA acts in PTB pathophysiology. Therefore, larger sample sets and replication studies are required to further elucidate our findings.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"21 3","pages":"e29"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Whole genome sequence analyses of thermotolerant Bacillus sp. isolates from food. 耐高温芽孢杆菌全基因组序列分析。

Genomics & informatics Pub Date : 2023-09-01 Epub Date: 2023-09-27 DOI: 10.5808/gi.23030

Phornphan Sornchuer, Kritsakorn Saninjuk, Pholawat Tingpej

{"title":"Whole genome sequence analyses of thermotolerant Bacillus sp. isolates from food.","authors":"Phornphan Sornchuer, Kritsakorn Saninjuk, Pholawat Tingpej","doi":"10.5808/gi.23030","DOIUrl":"10.5808/gi.23030","url":null,"abstract":"The Bacillus cereus group, also known as B. cereus sensu lato (B. cereus s.l.), is composed of various Bacillus species, some of which can cause diarrheal or emetic food poisoning. Several emerging highly heat-resistant Bacillus species have been identified, these include B. thermoamylovorans, B. sporothermodurans, and B. cytotoxicus NVH 391-98. Herein, we performed whole genome analysis of two thermotolerant Bacillus sp. isolates, Bacillus sp. B48 and Bacillus sp. B140, from an omelet with acacia leaves and fried rice, respectively. Phylogenomic analysis suggested that Bacillus sp. B48 and Bacillus sp. B140 are closely related to B. cereus and B. thuringiensis, respectively. Whole genome alignment of Bacillus sp. B48, Bacillus sp. B140, mesophilic strain B. cereus ATCC14579, and thermophilic strain B. cytotoxicus NVH 391-98 using the Mauve program revealed the presence of numerous homologous regions including genes responsible for heat shock in the dnaK gene cluster. However, the presence of a DUF4253 domain-containing protein was observed only in the genome of B. cereus ATCC14579 while the intracellular protease PfpI family was present only in the chromosome of B. cytotoxicus NVH 391-98. In addition, prophage Clp protease-like proteins were found in the genomes of both Bacillus sp. B48 and Bacillus sp. B140 but not in the genome of B. cereus ATCC14579. The genomic profiles of Bacillus sp. isolates were identified by using whole genome analysis especially those relating to heat-responsive gene clusters. The findings presented in this study lay the foundations for subsequent studies to reveal further insights into the molecular mechanisms of Bacillus species in terms of heat resistance mechanisms.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"21 3","pages":"e35"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular docking Study of Nuciferine as a Tyrosinase Inhibitor and Its Therapeutic Potential for Hyperpigmentation. 芥子碱作为酪氨酸酶抑制剂的分子对接研究及其对色素沉着过度的治疗潜力。

Genomics & informatics Pub Date : 2023-09-01 Epub Date: 2023-09-14 DOI: 10.5808/gi.23054

Veerabhuvaneshwari Veerichetty, Iswaryalakshmi Saravanabavan

{"title":"Molecular docking Study of Nuciferine as a Tyrosinase Inhibitor and Its Therapeutic Potential for Hyperpigmentation.","authors":"Veerabhuvaneshwari Veerichetty, Iswaryalakshmi Saravanabavan","doi":"10.5808/gi.23054","DOIUrl":"10.5808/gi.23054","url":null,"abstract":"Melanin is synthesized by tyrosinase to protect the skin from ultraviolet light. However, overproduction and accumulation of melanin can result in hyperpigmentation and skin melanoma. Tyrosinase inhibitors are commonly used in the treatment of hyperpigmentation. Natural tyrosinase inhibitors are often favored over synthetic ones due to the potential side effects of the latter, which can include skin irritation, allergies, and other adverse reactions. Nuciferine, an alkaloid derived from Nelumbo nucifera, exhibits potent antioxidant and anti-proliferative properties. This study focused on the in silico screening of nuciferine for anti-tyrosinase activity, using kojic acid, ascorbic acid, and resorcinol as standards. The tyrosinase protein target was selected through homology modeling. The residues of the substrate binding pocket and active site pockets were identified for the purposes of grid box optimization and docking. Nuciferine demonstrated a binding energy of -7.0 kcal/mol and a Ki of 5 µM, both of which were comparatively higher than the corresponding values of kojic acid, which showed -5.3 kcal/mol and 122 µM respectively. Therefore, nuciferine is a potent natural tyrosinase inhibitor and shows promising potential for application in the treatment of hyperpigmentation and skin melanoma.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"21 3","pages":"e43"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In-silico and structure-based assessment to evaluate pathogenicity of missense mutations associated with non-small cell lung cancer identified in the Eph-ephrin class of proteins. 对Eph-ephrin类蛋白质中鉴定的与非小细胞肺癌癌症相关的错义突变的致病性进行原位和结构评估。

Genomics & informatics Pub Date : 2023-09-01 Epub Date: 2023-09-27 DOI: 10.5808/gi.22069

Shubhashish Chakraborty, Reshita Baruah, Neha Mishra, Ashok K Varma

{"title":"In-silico and structure-based assessment to evaluate pathogenicity of missense mutations associated with non-small cell lung cancer identified in the Eph-ephrin class of proteins.","authors":"Shubhashish Chakraborty, Reshita Baruah, Neha Mishra, Ashok K Varma","doi":"10.5808/gi.22069","DOIUrl":"10.5808/gi.22069","url":null,"abstract":"Ephs belong to the largest family of receptor tyrosine kinase and are highly conserved both sequentially and structurally. The structural organization of Eph is similar to other receptor tyrosine kinases; constituting the extracellular ligand binding domain, a fibronectin domain followed by intracellular juxtamembrane kinase, and SAM domain. Eph binds to respective ephrin ligand, through the ligand binding domain and forms a tetrameric complex to activate the kinase domain. Eph-ephrin regulates many downstream pathways that lead to physiological events such as cell migration, proliferation, and growth. Therefore, considering the importance of Eph-ephrin class of protein in tumorigenesis, 7,620 clinically reported missense mutations belonging to the class of variables of unknown significance were retrieved from cBioPortal and evaluated for pathogenicity. Thirty-two mutations predicted to be pathogenic using SIFT, Polyphen-2, PROVEAN, SNPs&GO, PMut, iSTABLE, and PremPS in-silico tools were found located either in critical functional regions or encompassing interactions at the binding interface of Eph-ephrin. However, seven were reported in nonsmall cell lung cancer (NSCLC). Considering the relevance of receptor tyrosine kinases and Eph in NSCLC, these seven mutations were assessed for change in the folding pattern using molecular dynamic simulation. Structural alterations, stability, flexibility, compactness, and solvent-exposed area was observed in EphA3 Trp790Cys, EphA7 Leu749Phe, EphB1 Gly685Cys, EphB4 Val748Ala, and Ephrin A2 Trp112Cys. Hence, it can be concluded that the evaluated mutations have potential to alter the folding pattern and thus can be further validated by in-vitro, structural and in-vivo studies for clinical management.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"21 3","pages":"e30"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

M Protein from Dengue virus oligomerizes to pentameric channel protein: in silico analysis study. 登革热病毒M蛋白低聚为五聚体通道蛋白：计算机分析研究。

Genomics & informatics Pub Date : 2023-09-01 Epub Date: 2023-09-27 DOI: 10.5808/gi.23035

Ayesha Zeba, Kanagaraj Sekar, Anjali Ganjiwale

{"title":"M Protein from Dengue virus oligomerizes to pentameric channel protein: in silico analysis study.","authors":"Ayesha Zeba, Kanagaraj Sekar, Anjali Ganjiwale","doi":"10.5808/gi.23035","DOIUrl":"10.5808/gi.23035","url":null,"abstract":"The Dengue virus M protein is a 75 amino acid polypeptide with two helical transmembranes (TM). The TM domain oligomerizes to form an ion channel, facilitating viral release from the host cells. The M protein has a critical role in the virus entry and life cycle, making it a potent drug target. The oligomerization of the monomeric protein was studied using ab initio modeling and molecular dynamics (MD) simulation in an implicit membrane environment. The representative structures obtained showed pentamer as the most stable oligomeric state, resembling an ion channel. Glutamic acid, threonine, serine, tryptophan, alanine, isoleucine form the pore-lining residues of the pentameric channel, conferring an overall negative charge to the channel with approximate length of 51.9 Å. Residue interaction analysis (RIN) for M protein shows that Ala94, Leu95, Ser112, Glu124, and Phe155 are the central hub residues representing the physicochemical interactions between domains. The virtual screening with 165 different ion channel inhibitors from the ion channel library shows monovalent ion channel blockers, namely lumacaftor, glipizide, gliquidone, glisoxepide, and azelnidipine to be the inhibitors with high docking scores. Understanding the three-dimensional structure of M protein will help design therapeutics and vaccines for Dengue infection.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"21 3","pages":"e41"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41184733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0