Evolutionary Bioinformatics Online最新文献

{"title":"Distribution, Phylogeny and Evolution of Clinical and Environmental <i>Vibrio vulnificus</i> Antibiotic-Resistant Genes.","authors":"Nan Geng,&nbsp;Guojin Sun,&nbsp;Wen-Jia Liu,&nbsp;Bin-Cheng Gao,&nbsp;Cong Sun,&nbsp;Cundong Xu,&nbsp;Ertian Hua,&nbsp;Lin Xu","doi":"10.1177/11769343221134400","DOIUrl":"https://doi.org/10.1177/11769343221134400","url":null,"abstract":"<p><p><i>Vibrio vulnificus</i> is an emergent marine pathogen and is the cause of a deadly septicemia. However, the evolution mechanism of antibiotic-resistant genes (ARGs) is still unclear. Twenty-two high-quality complete genomes of <i>V. vulnificus</i> were obtained and grouped into 16 clinical isolates and 6 environmental isolates. Genomic annotations found 23 ARG orthologous genes, among which 14 ARGs were shared by <i>V. vulnificus</i> and other <i>Vibrio</i> members. Furthermore, those ARGs were located in their chromosomes, rather than in the plasmids. Phylogenomic reconstruction based on single-copy orthologous protein sequences and ARG protein sequences revealed that clinical and environmental <i>V. vulnificus</i> isolates were in a scattered distribution. The calculation of non-synonymous and synonymous substitutions indicated that most of ARGs evolved under purifying selection with the <i>Ka</i>/<i>Ks</i> ratios lower than one, while <i>h-ns, rsmA</i>, and <i>soxR</i> in several clinical isolates evolved under the positive selection with <i>Ka</i>/<i>Ks</i> ratios >1. Our result indicated that <i>V. vulnificus</i> antibiotic-resistant armory was not only confined to clinical isolates, but to environmental ones as well and clinical isolates inclined to accumulate beneficial non-synonymous substitutions that could be retained to improve competitiveness.</p>","PeriodicalId":136690,"journal":{"name":"Evolutionary Bioinformatics Online","volume":" ","pages":"11769343221134400"},"PeriodicalIF":2.6,"publicationDate":"2022-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e0/04/10.1177_11769343221134400.PMC9669696.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40477344","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}

{"title":"Bioinformatics-based Characterization of the Sequence Variability of Zika Virus Polyprotein and Envelope Protein (E).","authors":"Carlos Polanco,&nbsp;Vladimir N Uversky,&nbsp;Alberto Huberman,&nbsp;Gilberto Vargas-Alarcón,&nbsp;Jorge Alberto Castañón González,&nbsp;Thomas Buhse,&nbsp;Enrique Hernández Lemus,&nbsp;Martha Rios Castro,&nbsp;Erika Jeannette López Oliva,&nbsp;Sergio Enrique Solís Nájera","doi":"10.1177/11769343221130730","DOIUrl":"https://doi.org/10.1177/11769343221130730","url":null,"abstract":"<p><strong>Background: </strong>Zika virus, which is widely spread and infects humans through the bites of <i>Aedes albopictus</i> and <i>Aedes aegypti</i> female mosquitoes, represents a serious global health issue.</p><p><strong>Objective: </strong>The objective of the present study is to computationally characterize Zika virus polyproteins (UniProt Name: PRO_0000443018 [residues 1-3423], PRO_0000445659 [residues 1-3423] and PRO_0000435828 [residues 1-3419]) and their envelope proteins using their physico-chemical properties.</p><p><strong>Methods: </strong>To achieve this, the Polarity Index Method (PIM) profile and the Protein Intrinsic Disorder Predisposition (PIDP) profile of 3 main groups of proteins were evaluated: structural proteins extracted from specific Databases, Zika virus polyproteins, and their envelope proteins (E) extracted from UniProt Database. Once the PIM profile of the Zika virus envelope proteins (E) was obtained and since the Zika virus polyproteins were also identified with this profile, the proteins defined as \"reviewed proteins\" extracted from the <i>UniProt Database</i> were searched for the similar PIM profile. Finally, the difference between the PIM profiles of the Zika virus polyproteins and their envelope proteins (E) was tested using 2 non-parametric statistical tests.</p><p><strong>Results: </strong>It was found and tested that the PIM profile is an efficient discriminant that allows obtaining a \"computational fingerprint\" of each Zika virus polyprotein from its envelope protein (E).</p><p><strong>Conclusion: </strong>PIM profile represents a computational tool, which can be used to effectively discover Zika virus polyproteins from Databases, from their envelope proteins (E) sequences.</p>","PeriodicalId":136690,"journal":{"name":"Evolutionary Bioinformatics Online","volume":" ","pages":"11769343221130730"},"PeriodicalIF":2.6,"publicationDate":"2022-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/07/0b/10.1177_11769343221130730.PMC9623037.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40665462","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}

{"title":"Integrated Analysis of Multi-Omics Data to Establish a Hypoxia-Related Prognostic Model in Osteosarcoma.","authors":"Ye Tong,&nbsp;Xiaoqing Zhang,&nbsp;Ye Zhou","doi":"10.1177/11769343221128537","DOIUrl":"https://doi.org/10.1177/11769343221128537","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is the most common malignant bone tumor in clinical practice, and currently, the ability to predict prognosis in the diagnosis of OS is limited. There is an urgent need to find new diagnostic methods and treatment strategies for OS.</p><p><strong>Material and methods: </strong>We downloaded the multi-omics data for OS from the TARGET database. Prognosis-associated methylation sites were used to identify clustered subtypes of OS, and OS was classified into 3 subtypes (C1, C2, C3). Survival analysis showed significant differences between the C3 subtype and the other subtypes. Subsequently, differentially expressed genes (DEGs) across subtypes were screened and subjected to pathway enrichment analysis.</p><p><strong>Results: </strong>A total of 249 DEGs were screened from C3 subtype to other subtypes. Metabolic pathway enrichment analysis showed that DEGs were significantly enriched to the hypoxic pathway. Based on univariate and multivariate COX regression analysis, 12 genes from the hypoxia pathway were further screened and used to construct hypoxia-related prognostic model (HRPM). External validation of the HRPM was performed on the GSE21257 dataset. Finally, differences in survival and immune infiltration between high and low risk score groups were compared.</p><p><strong>Conclusion: </strong>In summary, we proposed a hypoxia-associated risk model based on a 12-gene expression signature, which is potentially valuable for prognostic diagnosis of patients with OS.</p>","PeriodicalId":136690,"journal":{"name":"Evolutionary Bioinformatics Online","volume":" ","pages":"11769343221128537"},"PeriodicalIF":2.6,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/39/10.1177_11769343221128537.PMC9618759.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40663018","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}

{"title":"Construction of a Prognostic Nomogram Based on Autophagy-Related Genes for Children With Neuroblastoma.","authors":"Guogang Ye,&nbsp;Yue Wang","doi":"10.1177/11769343221120960","DOIUrl":"https://doi.org/10.1177/11769343221120960","url":null,"abstract":"<p><p>Neuroblastoma (NB) is the most common solid malignancy in children. MYCN gene amplification is the most relevant genetic alteration in patients with NB and is associated with poor prognosis. Autophagy plays specific roles in the occurrence, development, and progression of NB. Here, we aimed to identify and assess the prognostic effects of autophagy-related genes (ARGs) in patients with NB and MYCN gene amplification. Differentially expressed ARGs were identified in patients with NB with and without MYCN gene amplification, and the ARG expression patterns and related clinical data from the Therapeutically Applicable Research to Generate Effective Treatments database were used as the training cohort. Least absolute shrinkage and selection operator analyses were used to identify prognostic ARGs associated with event-free survival (EFS), and a prognostic risk score model was developed. Model performance was assessed using the Kaplan-Meier method and receiver operating characteristic (ROC) curves. The prognostic ARG mode l was verified using the validation cohort dataset, GSE49710. Finally, a nomogram was constructed by combining the ARGbased risk score with clinicopathological factors. Three ARGs (GABARAPL1, NBR1, and PINK1) were selected to build a prognostic risk score model. The EFS in the low-risk group was significantly better than that in the high-risk group in both the training and validation cohorts. A nomogram incorporating the prognostic risk score, age, and International Neuroblastoma Staging System stage showed a favorable predictive ability for EFS rates according to the area under the ROC curve at 3 years (AUC = 0.787) and 5 years (AUC = 0.787). The nomogram demonstrated good discrimination and calibration. Our risk score model for the 3 ARGs can be used as an independent prognostic factor in patients with NB and MYCN gene amplification. The model can accurately predict the 3- and 5-year survival rates.</p>","PeriodicalId":136690,"journal":{"name":"Evolutionary Bioinformatics Online","volume":" ","pages":"11769343221120960"},"PeriodicalIF":2.6,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ae/46/10.1177_11769343221120960.PMC9421005.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40335973","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}

{"title":"Bioinformatics Analysis Identifies Potential Related Genes in the Pathogenesis of Intrauterine Fetal Growth Retardation.","authors":"Chao Xiao,&nbsp;Yao Wang,&nbsp;Yuchao Fan","doi":"10.1177/11769343221112780","DOIUrl":"https://doi.org/10.1177/11769343221112780","url":null,"abstract":"<p><strong>Background: </strong>Intrauterine growth retardation (IUGR) affects approximately 10% to 15% of all pregnancies worldwide. IUGR is not only associated with stillbirth and newborn death, but also the delay of cognition in childhood and the promotion of metabolic and vascular disorders in adulthood. Figuring out the mechanism of IUGR is rather meaningful and valuable.</p><p><strong>Methods: </strong>Datasets related to IUGR were searched in the Gene Expression Omnibus website. Principal component analysis (PCA) was used for normalization. Differential expressed genes (DEGs) were screened out using the ggpot2 tool. DEGs were used to conduct Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses, and protein-protein interaction (PPI) analysis. IUGR related genes were searched in the OMIM website to look for the intersection with the DEGs. The DEGs were analyzed for tissue-specific expression by the online resource BioGPS. The results were displayed through volcano map, Venn map, box plot, heat map, and GSEA enrichment plots drawn by R language packages.</p><p><strong>Results: </strong>Eleven DEGs were screened out of 2 datasets. One hundred ninety-five genes related to IUGR in OMIM were retrieved. EGR2 was the only intersection gene that was found in both groups. Genes associated with placental tissue expression include COL17A1, HSD11B1, and LGALS14. Molecular functions of the DEGs are related to the oxidoreductase activity. The following 4 signaling pathways, reactome signaling by interleukins, reactome collagen degradation, Naba secreted factors, and PID NFAT tfpathway, were enriched by GSEA. Two critical modules comprising 5 up-regulated genes (LEP, PRL, TAC3, MMP14, and ADAMTS4) and 4 down-regulated genes (TIMP4, FOS, CCK, and KISS1) were identified by PPI analysis. Finally, we identified 6 genes (PRL, LGALS14, EGR2, TAC3, LEP, and KISS1) that are potentially relevant to the pathophysiology of IUGR.</p><p><strong>Conclusion: </strong>The candidate down-regulated genes LGALS14 and KISS1, as well as the up-regulated genes PRL, EGR2, TAC3, and LEP, were found to be closely related to IUGR by bioinformatics analysis. These hub genes are related to hypoxia and oxidoreductase activities in placental development. We provide useful and novel information to explore the potential mechanism of IUGR and make efforts to the prevention of IUGR.</p>","PeriodicalId":136690,"journal":{"name":"Evolutionary Bioinformatics Online","volume":" ","pages":"11769343221112780"},"PeriodicalIF":2.6,"publicationDate":"2022-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/4d/10.1177_11769343221112780.PMC9340335.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40598931","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}

{"title":"Analysis of Competitive Endogenous RNA Regulatory Network of Exosomal Breast Cancer Based on exoRBase.","authors":"Kangle Zhu,&nbsp;Qingqing Wang,&nbsp;Lian Wang","doi":"10.1177/11769343221113286","DOIUrl":"https://doi.org/10.1177/11769343221113286","url":null,"abstract":"<p><strong>Objective: </strong>To construct a competitive endogenous RNA (ceRNA) regulatory network derived from exosomes of human breast cancer (BC) by using the exoRbase database, to explore the possible pathogenesis of BC, and to develop new targets for future diagnosis and treatment.</p><p><strong>Methods: </strong>The exosomal gene sequencing data of BC patients and normal controls were downloaded from the exoRbase database, and the expression profiles of exosomal mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) were analyzed by using R language. Use Targetscan and miRanda database to jointly predict and differentially express miRNA (microRNA), miRNA combined with mRNA. The miRcode database was used to predict the miRNA combined with differentially expressed lncRNA, and the starBase database was used to predict the miRNA combined with circRNA in the difference table. The related mRNA, circRNA, lncRNA, and their corresponding miRNA prediction data were imported into Cytoscape software to visualize the ceRNA network. Enrichment analysis and visualization of KEGG were carried out using KOBAS. Hub gene was determined by Cytohubba plug-in.</p><p><strong>Results: </strong>Forty-two differentially expressed mRNA, 43 differentially expressed circRNA, and 26 differentially expressed lncRNA were screened out. The ceRNA network was constructed by using Cytoscape software, including 19 mRNA nodes, 2 lncRNA nodes, 8 circRNA nodes, and 41 miRNA nodes. KEGG enrichment analysis showed that differentially expressed mRNA in the regulatory network mainly enriched the p53 signaling pathway. Find the key Hub gene PTEN.</p><p><strong>Conclusion: </strong>The ceRNA regulatory network in blood exosomes of BC patients has been successfully constructed in this study, which provides an exact target for the diagnosis and treatment of BC.</p>","PeriodicalId":136690,"journal":{"name":"Evolutionary Bioinformatics Online","volume":" ","pages":"11769343221113286"},"PeriodicalIF":2.6,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4e/75/10.1177_11769343221113286.PMC9309761.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40639002","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}

{"title":"BioAlign: An Accurate Global PPI Network Alignment Algorithm.","authors":"Umair Ayub,&nbsp;Hammad Naveed","doi":"10.1177/11769343221110658","DOIUrl":"https://doi.org/10.1177/11769343221110658","url":null,"abstract":"<p><strong>Motivation: </strong>The advancement of high-throughput PPI profiling techniques results in generating a large amount of PPI data. The alignment of the PPI networks uncovers the relationship between the species that can help understand the biological systems. The comparative study reveals the conserved biological interactions of the proteins across the species. It can also help study the biological pathways and signal networks of the cells. Although several network alignment algorithms are developed to study and compare the PPI data, the development of the aligner that aligns the PPI networks with high biological similarity and coverage is still challenging.</p><p><strong>Results: </strong>This paper presents a novel global network alignment algorithm, BioAlign, that incorporates a significant amount of biological information. Existing studies use global sequence and/or 3D-structure similarity to align the PPI networks. In contrast, BioAlign uses the local sequence similarity, predicted secondary structure motifs, and remote homology in addition to global sequence and 3D-structure similarity. The extra sources of biological information help BioAlign to align the proteins with high biological similarity. BioAlign produces significantly better results in terms of AFS and Coverage (6-32 and 7-34 with respect to MF and BP, respectively) than the existing algorithms. BioAlign aligns a much larger number of proteins that have high biological similarities as compared to the existing aligners. BioAlign helps in studying the functionally similar protein pairs across the species.</p>","PeriodicalId":136690,"journal":{"name":"Evolutionary Bioinformatics Online","volume":" ","pages":"11769343221110658"},"PeriodicalIF":2.6,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/41/3e/10.1177_11769343221110658.PMC9309777.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40637544","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}

{"title":"Metagenomic Sequencing and Histology on a Chronic Wound Identified Epstein-Barr Virus-Associated Lymphoma.","authors":"Wan-Ting Yang,&nbsp;I Chiang,&nbsp;Chien-Hao Tseng,&nbsp;Chun Cheng,&nbsp;Jyun-Hong Lin,&nbsp;Po-Yu Liu,&nbsp;Yao-Ting Huang","doi":"10.1177/11769343221110663","DOIUrl":"https://doi.org/10.1177/11769343221110663","url":null,"abstract":"<p><p>Accurate diagnosis of chronic, non-healing wounds is challenging and time-consuming because it can be caused by a variety of etiologies. This brief report presents an unusual case of a chronic wound lasting for 10 months investigated by deep metagenomic sequencing. Epstein-Barr virus (EBV) was identified in the wound and subsequently validated by in situ hybridization. Histopathologic examination eventually revealed that the non-healing wound was due to an EBV-associated NK/T cell lymphoma. By identifying mutations across the viral genome, the virus was classified as Type I EBV and clustered with others of geographic proximity. Our results suggest that metagenomic shotgun sequencing can not only rapidly and accurately identify the presence of underlying pathogens but also provide strain-level resolution for the surveillance of viral epidemiology.</p>","PeriodicalId":136690,"journal":{"name":"Evolutionary Bioinformatics Online","volume":" ","pages":"11769343221110663"},"PeriodicalIF":2.6,"publicationDate":"2022-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/48/10.1177_11769343221110663.PMC9297456.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40645311","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}

{"title":"Mononucleotide A-repeats may Play a Regulatory Role in Endothermic Housekeeping Genes.","authors":"Jatuphol Pholtaisong,&nbsp;Nachol Chaiyaratana,&nbsp;Chatchawit Aporntewan,&nbsp;Apiwat Mutirangura","doi":"10.1177/11769343221110656","DOIUrl":"https://doi.org/10.1177/11769343221110656","url":null,"abstract":"<p><strong>Background: </strong>Coding and non-coding short tandem repeats (STRs) facilitate a great diversity of phenotypic traits. The imbalance of mononucleotide A-repeats around transcription start sites (TSSs) was found in 3 mammals: <i>H. sapiens, M. musculus</i>, and <i>R. norvegicus</i>.</p><p><strong>Principal findings: </strong>We found that the imbalance pattern originated in some vertebrates. A similar pattern was observed in mammals and birds, but not in amphibians and reptiles. We proposed that the enriched A-repeats upstream of TSSs is a novel hallmark of endotherms or warm-blooded animals. Gene ontology analysis indicates that the primary function of upstream A-repeats involves metabolism, cellular transportation, and sensory perception (smell and chemical stimulus) through housekeeping genes.</p><p><strong>Conclusions: </strong>Upstream A-repeats may play a regulatory role in the metabolic process of endothermic animals.</p>","PeriodicalId":136690,"journal":{"name":"Evolutionary Bioinformatics Online","volume":" ","pages":"11769343221110656"},"PeriodicalIF":2.6,"publicationDate":"2022-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c4/87/10.1177_11769343221110656.PMC9290108.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40541100","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}

{"title":"Computational Structural and Functional Analyses of ORF10 in Novel Coronavirus SARS-CoV-2 Variants to Understand Evolutionary Dynamics.","authors":"Seema Mishra","doi":"10.1177/11769343221108218","DOIUrl":"https://doi.org/10.1177/11769343221108218","url":null,"abstract":"<p><strong>Introduction: </strong>In an effort to combat SARS-CoV-2 through multi-subunit vaccine design, during studies using whole genome and immunome, ORF10, located at the 3' end of the genome, displayed unique features. It showed no homology to any known protein in other organisms, including SARS-CoV. It was observed that its nucleotide sequence is 100% identical in the SARS-CoV-2 genomes sourced worldwide, even in the recent-most VoCs and VoIs of B.1.1.529 (Omicron), B.1.617 (Delta), B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma) lineages, implicating its constant nature throughout the evolution of deadly variants.</p><p><strong>Aim: </strong>The structure and function of SARS-CoV-2 ORF10 and the role it may play in the viral evolution is yet to be understood clearly. The aim of this study is to predict its structure, function, and understand evolutionary dynamics on the basis of mutations and likely heightened immune responses in the immunopathogenesis of this deadly virus.</p><p><strong>Methods: </strong>Sequence analysis, ab-initio structure modeling and an understanding of the impact of likely substitutions in key regions of protein was carried out. Analyses of viral T cell epitopes and primary anchor residue mutations was done to understand the role it may play in the evolution as a molecule with likely enhanced immune response and consequent immunopathogenesis.</p><p><strong>Results: </strong>Few amino acid substitution mutations are observed, most probably due to the ribosomal frameshifting, and these mutations may not be detrimental to its functioning. As ORF10 is observed to be an expressed protein, ab-initio structure modeling shows that it comprises mainly an α-helical region and maybe an ER-targeted membrane mini-protein. Analyzing the whole proteome, it is observed that ORF10 presents amongst the highest number of likely promiscuous and immunogenic CTL epitopes, specifically 11 out of 30 promiscuous ones and 9 out of these 11, immunogenic CTL epitopes. Reactive T cells to these epitopes have been uncovered in independent studies. Majority of these epitopes are located on the α-helix region of its structure, and the substitution mutations of primary anchor residues in these epitopes do not affect immunogenicity. Its conserved nucleotide sequence throughout the evolution and diversification of virus into several variants is a puzzle yet to be solved.</p><p><strong>Conclusions: </strong>On the basis of its sequence, structure, and epitope mapping, it is concluded that it may function like those mini-proteins used to boost immune responses in medical applications. Due to the complete nucleotide sequence conservation even a few years after SARS-CoV-2 genome was first sequenced, it poses a unique puzzle to be solved, in view of the evolutionary dynamics of variants emerging in the populations worldwide.</p>","PeriodicalId":136690,"journal":{"name":"Evolutionary Bioinformatics Online","volume":" ","pages":"11769343221108218"},"PeriodicalIF":2.6,"publicationDate":"2022-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/7d/10.1177_11769343221108218.PMC9336178.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40660247","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}