Evolutionary Bioinformatics最新文献

{"title":"Toward a Better Understanding of G4 Evolution in the 3 Living Kingdoms.","authors":"Anaïs Vannutelli, Aïda Ouangraoua, Jean-Pierre Perreault","doi":"10.1177/11769343231212075","DOIUrl":"10.1177/11769343231212075","url":null,"abstract":"Background: G-quadruplexes (G4s) are secondary structures in DNA and RNA that impact various cellular processes, such as transcription, splicing, and translation. Due to their numerous functions, G4s are involved in many diseases, making their study important. Yet, G4s evolution remains largely unknown, due to their low sequence similarity and the poor quality of their sequence alignments across several species. To address this, we designed a strategy that avoids direct G4s alignment to study G4s evolution in the 3 species kingdoms. We also explored the coevolution between RBPs and G4s. Methods: We retrieved one-to-one orthologous genes from the Ensembl Compara database and computed groups of one-to-one orthologous genes. For each group, we aligned gene sequences and identified G4 families as groups of overlapping G4s in the alignment. We analyzed these G4 families using Count, a tool to infer feature evolution into a gene or a species tree. Additionally, we utilized these G4 families to predict G4s by homology. To establish a control dataset, we performed mono-, di- and tri-nucleotide shuffling. Results: Only a few conserved G4s occur among all living kingdoms. In eukaryotes, G4s exhibit slight conservation among vertebrates, and few are conserved between plants. In archaea and bacteria, at most, only 2 G4s are common. The G4 homology-based prediction increases the number of conserved G4s in common ancestors. The coevolution between RNA-binding proteins and G4s was investigated and revealed a modest impact of RNA-binding proteins evolution on G4 evolution. However, the details of this relationship remain unclear. Conclusion: Even if G4 evolution still eludes us, the present study provides key information to compute groups of homologous G4 and to reveal the evolution history of G4 families.","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"19 ","pages":"11769343231212075"},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective Phylodynamic and Phylogeographic Analysis of the Bluetongue Virus in Tunisia.","authors":"Oussema Souiai, Marwa Arbi, Mariem Hanachi, Ameny Sallami, Imen Larbi, Melek Chaouch, Emna Harigua-Souiai, Alia Benkahla","doi":"10.1177/11769343231212266","DOIUrl":"10.1177/11769343231212266","url":null,"abstract":"<p><p>Bluetongue virus (BTV) is an arbovirus considered as a major threat for the global livestock economy. Since 1999, Tunisia has experienced several incursions of BTV, during which numerous cases of infection and mortality have been reported. However, the geographical origin and epidemiological characteristics of these incursions remained unclear. To understand the evolutionary history of BTV emergence in Tunisia, we extracted from Genbank the segment 6 sequences of 7 BTV strains isolated in Tunisia during the period 2000 to 2017 and blasted them to obtain a final dataset of 67 sequences. We subjected the dataset to a Bayesian phylogeography framework inferring geographical origin and serotype as phylodynamic models. Our results suggest that BTV-2 was first introduced in Tunisia in the 1960s and that since 1990s, the country has witnessed the emergence of other typical and atypical BTV serotypes notably BTV-1, BTV-3 and BTV-Y. The reported serotypes have a diverse geographical origin and have been transmitted to Tunisia from countries in the Mediterranean Basin. Interserotype reassortments have been identified among BTV-1, BTV-2 and BTV-Y. This study has provided new insights on the temporal and geographical origin of BTV in Tunisia, suggesting the contribution of animal trade and environment conditions in virus spread.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"19 ","pages":"11769343231212266"},"PeriodicalIF":2.6,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics Analysis of Prognostic Significance and Immune Infiltration of FASTK Family Members in Kidney Renal Clear Cell Carcinoma.","authors":"Guanghui Zhong, Dali Wu, Haiping Chen, Lingfei Yan, Qi Xiang, Yufeng Liu, Tao Wang","doi":"10.1177/11769343231212078","DOIUrl":"10.1177/11769343231212078","url":null,"abstract":"<p><strong>Objective: </strong>The Fas-activated serine/threonine kinase (FASTK) family of proteins has been recently found to be able to regulate mitochondrial gene expression post-transcriptionally. Nonetheless, there is a paucity of study about the role of the FASTK family in kidney renal clear cell carcinoma (KIRC). This study was conducted to explore the correlation of FASTK family genes with expression, prognosis, and immune infiltration in KIRC.</p><p><strong>Methods: </strong>We collected the data from the UALCAN, GeneMANIA, STRING, CancerSEA, cBioPortal, Kaplan-Meier plotter, GEPIA, TISIDB and TIMER databases to evaluate the genetic alterations, differential expression, prognostic significance, and immune cell infiltration of FASTKs in patients with KIRC.</p><p><strong>Results: </strong>In tumor tissues of KIRC, the mRNA expression level of FASTK and TBRG4 was elevated, whereas that of FASTKD1, FASTKD2, and FASTKD5 was lowered compared with normal tissues (<i>P</i> < .05). Patients with KIRC and high FASTK and Transforming growth factor β regulator 4 (TBRG4) expression had worse overall survival (OS) and disease specific survival (DFS), while those with lower expression of FASTKD2/3/5 had worse outcomes. FASTK was positively correlated with DNA damage. FASTKD1 was positively related to differentiation. FASTKD2 was inversely related to proliferation and FASTKD5 was inversely related to invasion and EMT in KIRC cells. FASTK expression in KIRC was inversely linked to the presence of several immune cells including Tgd, macrophages, Tcm, and Mast cells (<i>P</i> < .05).</p><p><strong>Conclusions: </strong>Our research provided fresh insight and in-depth analysis to the selection of prognostic biological markers of FASTK family members in KIRC.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"19 ","pages":"11769343231212078"},"PeriodicalIF":2.6,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Worldwide Correlations Support COVID-19 Seasonal Behavior and Impact of Global Change.","authors":"Nicolas Hernandez, Gustavo Caetano-Anollés","doi":"10.1177/11769343231169377","DOIUrl":"10.1177/11769343231169377","url":null,"abstract":"<p><p>Many viral diseases exhibit seasonal behavior and can be affected by environmental stressors. Using time-series correlation charts extrapolated from worldwide data, we provide strong support for the seasonal development of COVID-19 regardless of the immunity of the population, behavioral changes, and the periodic appearance of new variants with higher rates of infectivity and transmissibility. Statistically significant latitudinal gradients were also observed with indicators of global change. Using the Environmental Protection Index (EPI) and State of Global Air (SoGA) metrics, a bilateral analysis of environmental health and ecosystem vitality effects showed associations with COVID-19 transmission. Air quality, pollution emissions, and other indicators showed strong correlations with COVID-19 incidence and mortality. Remarkably, EPI category and performance indicators also correlated with latitude, suggesting cultural and psychological diversity in human populations not only impact wealth and happiness but also planetary health at latitudinal level. Looking forward, we conclude there will be a need to disentangle the seasonal and global change effects of COVID-19 noting that countries that go against the health of the planet affect health in general.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"19 ","pages":"11769343231169377"},"PeriodicalIF":1.7,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/2d/10.1177_11769343231169377.PMC10113908.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9443665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Biological Processes of Ferroptosis Involved in Pathogenesis of COVID-19 and Core Ferroptoic Genes Related With the Occurrence and Severity of This Disease.","authors":"Zhengzhong Zhang,&nbsp;Tingting Pang,&nbsp;Min Qi,&nbsp;Gengyun Sun","doi":"10.1177/11769343231153293","DOIUrl":"https://doi.org/10.1177/11769343231153293","url":null,"abstract":"<p><strong>Background: </strong>A worldwide outbreak of coronavirus disease 2019 (COVID-19) has resulted in millions of deaths. Ferroptosis is a form of iron-dependent cell death which is characterized by accumulation of lipid peroxides on cellular membranes, and is related with many physiological and pathophysiological processes of diseases such as cancer, inflammation and infection. However, the role of ferroptosis in COVID-19 has few been studied.</p><p><strong>Material and method: </strong>Based on the RNA-seq data of 100 COVID-19 cases and 26 Non-COVID-19 cases from GSE157103, we identified ferroptosis related differentially expressed genes (FRDEGs, adj.<i>P</i>-value < .05) using the \"Deseq2\" R package. By using the \"clusterProfiler\" R package, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Next, a protein-protein interaction (PPI) network of FRDEGs was constructed and top 30 hub genes were selected by cytoHubba in Cytoscape. Subsequently, we established a prediction model for COVID-19 by utilizing univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) regression. Based on core FRDEGs, COVID-19 patients were identified as two clusters using the \"ConsenesusClusterPlus\" R package. Finally, the miRNA-mRNA network was built by Targetscan online database and visualized by Cytoscape software.</p><p><strong>Results: </strong>A total of 119 FRDEGs were identified and the GO and KEGG enrichment analyses showed the most important biologic processes are oxidative stress response, MAPK and PI3K-AKT signaling pathway. The top 30 hub genes were selected, and finally, 7 core FRDEGs (JUN, MAPK8, VEGFA, CAV1, XBP1, HMOX1, and HSPB1) were found to be associated with the occurrence of COVID-19. Next, the two patterns of COVID-19 patients had constructed and the cluster A patients were likely to be more severe.</p><p><strong>Conclusion: </strong>Our study suggested that ferroptosis was involved in the pathogenesis of COVID-19 disease and the functions of core FRDEGs may become a new research aspect of this disease.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"19 ","pages":"11769343231153293"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/a8/10.1177_11769343231153293.PMC9929189.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10769063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pan-Genomic Analysis of <i>Corynebacterium striatum</i> Revealed its Genetic Characteristics as an Emerging Multidrug-Resistant Pathogen.","authors":"Junhui Qiu,&nbsp;Yulan Shi,&nbsp;Fei Zhao,&nbsp;Yi Xu,&nbsp;Hui Xu,&nbsp;Yan Dai,&nbsp;Yi Cao","doi":"10.1177/11769343231191481","DOIUrl":"https://doi.org/10.1177/11769343231191481","url":null,"abstract":"<p><p><i>Corynebacterium striatum</i> is a Gram-positive bacterium that is straight or slightly curved and non-spore-forming. Although it was originally believed to be a part of the normal microbiome of human skin, a growing number of studies have identified it as a cause of various chronic diseases, bacteremia, and respiratory infections. However, despite its increasing importance as a pathogen, the genetic characteristics of the pathogen population, such as genomic characteristics and differences, the types of resistance genes and virulence factors carried by the pathogen and their distribution in the population are poorly understood. To address these knowledge gaps, we conducted a pan-genomic analysis of 314 strains of <i>C. striatum</i> isolated from various tissues and geographic locations. Our analysis revealed that <i>C. striatum</i> has an open pan-genome, comprising 5692 gene families, including 1845 core gene families, 2362 accessory gene families, and 1485 unique gene families. We also found that <i>C. striatum</i> exhibits a high degree of diversity across different sources, but strains isolated from skin tissue are more conserved. Furthermore, we identified 53 drug resistance genes and 42 virulence factors by comparing the strains to the drug resistance gene database (CARD) and the pathogen virulence factor database (VFDB), respectively. We found that these genes and factors are widely distributed among <i>C. striatum</i>, with 77.7% of strains carrying 2 or more resistance genes and displaying primary resistance to aminoglycosides, tetracyclines, lincomycin, macrolides, and streptomycin. The virulence factors are primarily associated with pathogen survival within the host, iron uptake, pili, and early biofilm formation. In summary, our study provides insights into the population diversity, resistance genes, and virulence factors of<i>C. striatum</i> from different sources. Our findings could inform future research and clinical practices in the diagnosis, prevention, and treatment of <i>C. striatum</i>-associated diseases.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"19 ","pages":"11769343231191481"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/54/10.1177_11769343231191481.PMC10422898.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10305117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta, Delta, and Omicron, Deadliest Among SARS-CoV-2 Variants: A Computational Repurposing Approach.","authors":"Mohammad Mamun Alam,&nbsp;Sumaiya Binte Hannan,&nbsp;Tanvir Ahmed Saikat,&nbsp;Md Belayet Hasan Limon,&nbsp;Md Raihan Topu,&nbsp;Md Jowel Rana,&nbsp;Asma Salauddin,&nbsp;Sagar Bosu,&nbsp;Mohammed Ziaur Rahman","doi":"10.1177/11769343231182258","DOIUrl":"https://doi.org/10.1177/11769343231182258","url":null,"abstract":"<p><p>SARS-CoV-2 has been highly susceptible to mutations since its emergence in Wuhan, China, and its subsequent propagation due to containing an RNA as its genome. The emergence of variants with improved transmissibility still poses a grave threat to global health. The spike protein mutation is mainly responsible for higher transmissibility and risk severity. This study retrieved SARS-CoV-2 variants structural and nonstructural proteins (NSPs) sequences from several geographic locations, including Africa, Asia, Europe, Oceania, and North and South America. First, multiple sequence alignments with BioEdit and protein homology modeling were performed using the SWISS Model. Then the structure visualization and structural analysis were performed by superimposing against the Wuhan sequence by Pymol to retrieve the RMSD values. Sequence alignment revealed familiar, uncommon regional among variants and, interestingly, a few unique mutations in Beta, Delta, and Omicron. Structural analysis of such unique mutations revealed that they caused structural deviations in Beta, Delta, and Omicron spike proteins. In addition, these variants were more severe in terms of hospitalization, sickness, and higher mortality, which have a substantial relationship with the structural deviations because of those unique mutations. Such evidence provides insight into the SARS-CoV-2 spike protein vulnerability toward mutation and their structural and functional deviations, particularly in Beta, Delta, and Omicron, which might be the cause of their broader coverage. This knowledge can help us with regional vaccine strain selection, virus pathogenicity testing, diagnosis, and treatment with more specific vaccines.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"19 ","pages":"11769343231182258"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/a1/10.1177_11769343231182258.PMC10338667.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9826397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G-SAIP: Graphical Sequence Alignment Through Parallel Programming in the Post-Genomic Era.","authors":"Johan S Piña,&nbsp;Simon Orozco-Arias,&nbsp;Nicolas Tobón-Orozco,&nbsp;Leonardo Camargo-Forero,&nbsp;Reinel Tabares-Soto,&nbsp;Romain Guyot","doi":"10.1177/11769343221150585","DOIUrl":"https://doi.org/10.1177/11769343221150585","url":null,"abstract":"<p><p>A common task in bioinformatics is to compare DNA sequences to identify similarities between organisms at the sequence level. An approach to such comparison is the dot-plots, a 2-dimensional graphical representation to analyze DNA or protein alignments. Dot-plots alignment software existed before the sequencing revolution, and now there is an ongoing limitation when dealing with large-size sequences, resulting in very long execution times. High-Performance Computing (HPC) techniques have been successfully used in many applications to reduce computing times, but so far, very few applications for graphical sequence alignment using HPC have been reported. Here, we present G-SAIP (Graphical Sequence Alignment in Parallel), a software capable of spawning multiple distributed processes on CPUs, over a supercomputing infrastructure to speed up the execution time for dot-plot generation up to 1.68× compared with other current fastest tools, improve the efficiency for comparative structural genomic analysis, phylogenetics because the benefits of pairwise alignments for comparison between genomes, repetitive structure identification, and assembly quality checking.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"19 ","pages":"11769343221150585"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/44/80/10.1177_11769343221150585.PMC9871978.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10625078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanisms of the miR396b-<i>GRF1</i> Module Underlying Rooting Regulation in <i>Acer rubrum L.</i>","authors":"Manyu Zhang, Huiju Li, Huiyu Zhu, Hewen Zhao, Kezhong Zhang, Wei Ge","doi":"10.1177/11769343231211071","DOIUrl":"https://doi.org/10.1177/11769343231211071","url":null,"abstract":"Rooting and root development in Acer rubrum have important effects on overall growth. A. rubrum does not take root easily in natural conditions. In this study, the mechanisms of the miR396b- GRF1 module underlying rooting regulation in A. rubrum were studied. The subcellular localization and transcriptional activation of miR396b and its target gene growth regulating factor 1 ( GRF1) were investigated. These experiments showed that GRF1 was localized in the nucleus and had transcriptional activation activity. Functional validation experiments in transgenic plants demonstrated that overexpression of Ar-miR396b inhibited adventitious root growth, whereas overexpression of ArGRF1 increased adventitious root growth. These results help clarify the molecular regulatory mechanisms underlying adventitious root growth in A. rubrum and provide some new insights into the rooting rate in this species.","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"139 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135709845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico Analyses of All STAT3 Missense Variants Leading to Explore Divergent AD-HIES Clinical Phenotypes.","authors":"Mariam Mansouri,&nbsp;Ghyzlane El Haddoumi,&nbsp;Houda Bendani,&nbsp;Nasma Boumajdi,&nbsp;Mohammed Hakmi,&nbsp;Hanane Abbou,&nbsp;El Mehdi Bouricha,&nbsp;Boutaina Elgharbaoui,&nbsp;Souad Kartti,&nbsp;Rachid El Jaoudi,&nbsp;Lahcen Belyamani,&nbsp;Ilham Kandoussi,&nbsp;Azeddine Ibrahimi,&nbsp;Naima El Hafidi","doi":"10.1177/11769343231169374","DOIUrl":"https://doi.org/10.1177/11769343231169374","url":null,"abstract":"<p><p>Autosomal dominant hyper-IgE syndrome (AD-HIES) is linked to dominant negative mutations of the STAT3 protein whose molecular basis for dysfunction is unclear and presenting with a variety of clinical manifestations with only supportive treatment. To establish the relationship between the impact of STAT3 mutations in different domains and the severity of the clinical manifestations, 105 STAT3 mutations were analyzed for their impact on protein stability, flexibility, function, and binding affinity using in Silico approaches. Our results showed that 73% of the studied mutations have an impact on the physicochemical properties of the protein, altering the stability, flexibility and function to varying degrees. In particular, mutations affecting the DNA binding domain (DBD) and the Src Homology 2 (SH2) have a significant impact on the protein structure and disrupt its interaction either with DNA or other STAT3 to form a heterodomain complex, leading to severe clinical phenotypes. Collectively, this study suggests that there is a close relationship between the domain involving the mutation, the degree of variation in the properties of the protein and the degree of loss of function ranging from partial loss to complete loss, explaining the variability of clinical manifestations between mild and severe.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"19 ","pages":"11769343231169374"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ed/d8/10.1177_11769343231169374.PMC10134169.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9761963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}