Chao He, Bin Zhu, Wenwen Gao, Qianjin Wu, Changshui Zhang
{"title":"Study on Allele Specific Expression of Long-Term Residents in High Altitude Areas","authors":"Chao He, Bin Zhu, Wenwen Gao, Qianjin Wu, Changshui Zhang","doi":"10.1177/11769343241257344","DOIUrl":"https://doi.org/10.1177/11769343241257344","url":null,"abstract":"In diploid organisms, half of the chromosomes in each cell come from the father and half from the mother. Through previous studies, it was found that the paternal chromosome and the maternal chromosome can be regulated and expressed independently, leading to the emergence of allele specific expression (ASE). In this study, we analyzed the differential expression of alleles in the high-altitude population and the normal population based on the RNA sequencing data. Through gene cluster analysis and protein interaction network analysis, we found some changes occurred at the gene level, and some negative effects. During the study, we realized that the calmodulin homology domain may have a certain correlation with long-term survival at high altitude. The plateau environment is characterized by hypoxia, low air pressure, strong ultraviolet radiation, and low temperature. Accordingly, the genetic changes in the process of adaptation are mainly reflected in these characteristics. High altitude generation living is also highly related to cancer, immune disease, cardiovascular disease, neurological disease, endocrine disease, and other diseases. Therefore, the medical system in high altitude areas should pay more attention to these diseases.","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"80 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141190451","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}
Syed Shah Muhammad, Muhammad Shoaib, Muhammad Tariq Pervez
{"title":"An Integrated Framework for Analysis and Prediction of Impact of Single Nucleotide Polymorphism Associated with Human Diseases.","authors":"Syed Shah Muhammad, Muhammad Shoaib, Muhammad Tariq Pervez","doi":"10.1177/11769343241249916","DOIUrl":"10.1177/11769343241249916","url":null,"abstract":"<p><p>Single nucleotide polymorphisms are most common type of genetic variation in human genome. Analyzing genetic variants can help us better understand the genetic basis of diseases and develop predictive models which are useful to identify individuals who are at increased risk for certain diseases. Several SNP analysis tools have already been developed. For running these tools, the user needs to collect data from various databases. Secondly, often researchers have to use multiple variant analysis tools for cross validating their results and increase confidence in their findings. Extracting data from multiple databases and running multiple tools at a time, increases complexity and time required for analysis. There are some web-based tools that integrate multiple genetic variant databases and provide variant annotations for a few tools. These approaches have some limitations such as retrieving annotation information, filtering common pathogenic variants. The proposed web-based tool, namely IPSNP: An Integrated Platform for Predicting Impact of SNPs is written in Django which is a python-based framework. It uses RESTful API of MyVariant.info to extract annotation information of variants associated with a given gene, rsID, HGVS format variants specified in a VCF file for 29 tools. The results are in the form of a CSV file of predictions (1) derived from the consensus decision, (2) a file having annotations for the variants associated with the given gene, (3) a file showing variants declared as pathogenic commonly by the selected tools, and (4) a CSV file containing chromosome coordinates based on GRCh37 and GRCh38 genome assemblies, rsIDs and proteomic data, so that users may use tools of their choice and avoiding manual parameter collection for each tool. IPSNP is a valuable resource for researchers and clinicians and it can help to save time and effort in discovering the novel disease-associated variants and the development of personalized treatments.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"20 ","pages":"11769343241249916"},"PeriodicalIF":2.6,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913243","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}
Yihang Zhao, Hong Tang, Jianhua Xu, Feifei Sun, Yuanyuan Zhao, Yang Li
{"title":"HNF4A-Bridging the Gap Between Intestinal Metaplasia and Gastric Cancer","authors":"Yihang Zhao, Hong Tang, Jianhua Xu, Feifei Sun, Yuanyuan Zhao, Yang Li","doi":"10.1177/11769343241249017","DOIUrl":"https://doi.org/10.1177/11769343241249017","url":null,"abstract":"Background:Intestinal metaplasia (IM) of gastric epithelium has traditionally been regarded as an irreversible stage in the process of the Correa cascade. Exploring the potential molecular mechanism of IM is significant for effective gastric cancer prevention.Methods:The GSE78523 dataset, obtained from the Gene Expression Omnibus (GEO) database, was analyzed using RStudio software to identify the differently expressed genes (DEGs) between IM tissues and normal gastric epithelial tissues. Subsequently, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GESA), and protein-protein interaction (PPI) analysis were used to find potential genes. Additionally, the screened genes were analyzed for clinical, immunological, and genetic correlation aspects using single gene clinical correlation analysis (UALCAN), Tumor–Immune System Interactions Database (TISIDB), and validated through western blot experiments.Results:Enrichment analysis showed that the lipid metabolic pathway was significantly associated with IM tissues and the apolipoprotein B ( APOB) gene was identified in the subsequent analysis. Experiment results and correlation analysis showed that the expression of APOB was higher in IM tissues than in normal tissues. This elevated expression of APOB was also found to be associated with the expression levels of hepatocyte nuclear factor 4A ( HNF4A) gene. HNF4A was also found to be associated with immune cell infiltration to gastric cancer and was linked to the prognosis of gastric cancer patients. Moreover, HNF4A was also highly expressed in both IM tissues and gastric cancer cells.Conclusion:Our findings indicate that HNF4A regulates the microenvironment of lipid metabolism in IM tissues by targeting APOB. Higher expression of HNF4A tends to lead to a worse prognosis in gastric cancer patients implying it may serve as a predictive indicator for the progression from IM to gastric cancer.","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"52 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140803734","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}
Ahmed Kabir Refaya, Umashankar Vetrivel, Kannan Palaniyandi
{"title":"Genomic Characterization of IS6110 Insertions in Mycobacterium orygis","authors":"Ahmed Kabir Refaya, Umashankar Vetrivel, Kannan Palaniyandi","doi":"10.1177/11769343241240558","DOIUrl":"https://doi.org/10.1177/11769343241240558","url":null,"abstract":"Mycobacterium orygis, a subspecies of the Mycobacterium tuberculosis complex (MTBC), has emerged as a significant concern in the context of One Health, with implications for zoonosis or zooanthroponosis or both. MTBC strains are characterized by the unique insertion element IS 6110, which is widely used as a diagnostic marker. IS 6110 transposition drives genetic modifications in MTBC, imparting genome plasticity and profound biological consequences. While IS 6110 insertions are customarily found in the MTBC genomes, the evolutionary trajectory of strains seems to correlate with the number of IS 6110 copies, indicating enhanced adaptability with increasing copy numbers. Here, we present a comprehensive analysis of IS 6110 insertions in the M. orygis genome, utilizing ISMapper, and elucidate their genetic consequences in promoting successful host adaptation. Our study encompasses a panel of 67 paired-end reads, comprising 11 isolates from our laboratory and 56 sequences downloaded from public databases. Among these sequences, 91% exhibited high-copy, 4.5% low-copy, and 4.5% lacked IS 6110 insertions. We identified 255 insertion loci, including 141 intragenic and 114 intergenic insertions. Most of these loci were either unique or shared among a limited number of isolates, potentially influencing strain behavior. Furthermore, we conducted gene ontology and pathway analysis, using eggNOG-mapper 5.0, on the protein sequences disrupted by IS 6110 insertions, revealing 63 genes involved in diverse functions of Gene Ontology and 45 genes participating in various KEGG pathways. Our findings offer novel insights into IS 6110 insertions, their preferential insertion regions, and their impact on metabolic processes and pathways, providing valuable knowledge on the genetic changes underpinning IS 6110 transposition in M. orygis.","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"5 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579546","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}
Eshan Bundhoo, Anisah W Ghoorah, Yasmina Jaufeerally-Fakim
{"title":"Large-scale Pan Genomic Analysis of <i>Mycobacterium tuberculosis</i> Reveals Key Insights Into Molecular Evolutionary Rate of Specific Processes and Functions.","authors":"Eshan Bundhoo, Anisah W Ghoorah, Yasmina Jaufeerally-Fakim","doi":"10.1177/11769343241239463","DOIUrl":"10.1177/11769343241239463","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis</i> (Mtb) is the causative agent of tuberculosis (TB), an infectious disease that is a major killer worldwide. Due to selection pressure caused by the use of antibacterial drugs, Mtb is characterised by mutational events that have given rise to multi drug resistant (MDR) and extensively drug resistant (XDR) phenotypes. The rate at which mutations occur is an important factor in the study of molecular evolution, and it helps understand gene evolution. Within the same species, different protein-coding genes evolve at different rates. To estimate the rates of molecular evolution of protein-coding genes, a commonly used parameter is the ratio <i>d</i>N/<i>d</i>S, where <i>d</i>N is the rate of non-synonymous substitutions and <i>d</i>S is the rate of synonymous substitutions. Here, we determined the estimated rates of molecular evolution of select biological processes and molecular functions across 264 strains of Mtb. We also investigated the molecular evolutionary rates of core genes of Mtb by computing the <i>d</i>N/<i>d</i>S values, and estimated the pan genome of the 264 strains of Mtb. Our results show that the cellular amino acid metabolic process and the kinase activity function evolve at a significantly higher rate, while the carbohydrate metabolic process evolves at a significantly lower rate for <i>M. tuberculosi</i>s. These high rates of evolution correlate well with Mtb physiology and pathogenicity. We further propose that the core genome of <i>M. tuberculosis</i> likely experiences varying rates of molecular evolution which may drive an interplay between core genome and accessory genome during <i>M. tuberculosis</i> evolution.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"20 ","pages":"11769343241239463"},"PeriodicalIF":1.7,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295209","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":"Draft Genome Sequence of <i>Pantoea sp.</i> Strain MHSD4, a Bacterial Endophyte With Bioremediation Potential.","authors":"Dimpho Michelle Morobane, Khuthadzo Tshishonga, Mahloro Hope Serepa-Dlamini","doi":"10.1177/11769343231217908","DOIUrl":"10.1177/11769343231217908","url":null,"abstract":"<p><p><i>Pantoea</i> sp. strain MHSD4 is a bacterial endophyte isolated from the leaves of the medicinal plant <i>Pellaea calomelanos.</i> Here, we report on strain MHSD4 draft whole genome sequence and annotation. The draft genome size of <i>Pantoea</i> sp. strain MHSD4 is 4 647 677 bp with a G+C content of 54.2% and 41 contigs. The National Center for Biotechnology Information Prokaryotic Genome Annotation Pipeline tool predicted a total of 4395 genes inclusive of 4235 protein-coding genes, 87 total RNA genes, 14 non-coding (nc) RNAs and 70 tRNAs, and 73 pseudogenes. Biosynthesis pathways for naphthalene and anthracene degradation were identified. Putative genes involved in bioremediation such as <i>copA, copD, cueO, cueR, glnGm</i>, and <i>trxC</i> were identified. Putative genes involved in copper homeostasis and tolerance were identified which may suggest that <i>Pantoea</i> sp. strain MHSD4 has biotechnological potential for bioremediation of heavy metals.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"20 ","pages":"11769343231217908"},"PeriodicalIF":2.6,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10938601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133135","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":"A Comprehensive Analysis of 3 Moroccan Genomes Revealed Contributions From Both African and European Ancestries.","authors":"Nasma Boumajdi, Houda Bendani, Souad Kartti, Tarek Alouane, Lahcen Belyamani, Azeddine Ibrahimi","doi":"10.1177/11769343241229278","DOIUrl":"10.1177/11769343241229278","url":null,"abstract":"<p><p>Genetic variations in the human genome represent the differences in DNA sequence within individuals. This highlights the important role of whole human genome sequencing which has become the keystone for precision medicine and disease prediction. Morocco is an important hub for studying human population migration and mixing history. This study presents the analysis of 3 Moroccan genomes; the variant analysis revealed 6 379 606 single nucleotide variants (SNVs) and 1 050 577 small InDels. Of those identified SNVs, 219 152 were novel, with 1233 occurring in coding regions, and 5580 non-synonymous single nucleotide variants (nsSNP) variants were predicted to affect protein functions. The InDels produced 1055 coding variants and 454 non-3n length variants, and their size ranged from -49 and 49 bp. We further analysed the gene pathways of 8 novel coding variants found in the 3 genomes and revealed 5 genes involved in various diseases and biological pathways. We found that the Moroccan genomes share 92.78% of African ancestry, and 92.86% of Non-Finnish European ancestry, according to the gnomAD database. Then, population structure inference, by admixture analysis and network-based approach, revealed that the studied genomes form a mixed population structure, highlighting the increased genetic diversity in Morocco.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"20 ","pages":"11769343241229278"},"PeriodicalIF":2.6,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10848790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703947","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}
Yingjie Geng, Yu'e Han, Shujuan Wang, Jia Qi, Xiaoli Bi
{"title":"Screening and Validation of Key Genes of Autophagy in Acute Myocardial Infarction Based on Bioinformatics.","authors":"Yingjie Geng, Yu'e Han, Shujuan Wang, Jia Qi, Xiaoli Bi","doi":"10.1177/11769343241227331","DOIUrl":"10.1177/11769343241227331","url":null,"abstract":"<p><strong>Aims: </strong>Autophagy plays a significant role in the development of acute myocardial infarction (AMI), and cardiomyocyte autophagy is of major importance in maintaining cardiac function. We aimed to identify key genes associated with autophagy in AMI through bioinformatics analysis and verify them through clinical validation.</p><p><strong>Materials and methods: </strong>We downloaded an AMI expression profile dataset GSE166780 from Gene Expression Omnibus (GEO). Autophagy-associated genes potentially differentially expressed in AMI were screened using R software. Then, to identify key autophagy-related genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) analysis, Receiver Operating Characteristic (ROC) curve analysis, and correlation analysis were performed on the differentially expressed autophagy-related genes in AMI. Finally, we used quantificational real-time polymerase chain reaction (qRT-PCR) to verify the RNA expression of the screened key genes.</p><p><strong>Results: </strong>TSC2, HSPA8, and HIF1A were screened out as key autophagy-related genes. qRT-PCR results showed that the expression levels of HSPA8 and TSC2 in AMI blood samples were lower, while the expression level of HIF1A was higher than that in the healthy controls.</p><p><strong>Conclusions: </strong>TSC2, HSPA8, and HIF1A were identified as key autophagy-related genes in this study. They may influence the development of AMI through autophagy. These findings may help deepen our understanding of AMI and may be useful for the treatment of AMI.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"20 ","pages":"11769343241227331"},"PeriodicalIF":2.6,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10832399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681764","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":"Phylogenetic Analysis Provides Insight Into the Molecular Evolution of Nociception and Pain-Related Proteins.","authors":"Rujun Zhai, Qian Wang","doi":"10.1177/11769343231216914","DOIUrl":"https://doi.org/10.1177/11769343231216914","url":null,"abstract":"<p><p>Nociception and pain sensation are important neural processes in humans to avoid injury. Many proteins are involved in nociception and pain sensation in humans; however, the evolution of these proteins in animals is unknown. Here, we chose nociception- and pain-related proteins, including G protein-coupled receptors (GPCRs), ion channels (ICs), and neuropeptides (NPs), which are reportedly associated with nociception and pain in humans, and identified their homologs in various animals by BLAST, phylogenetic analysis and protein architecture comparison to reveal their evolution from protozoans to humans. We found that the homologs of transient receptor potential channel A 1 (TRPA1), TRAPM, acid-sensing IC (ASIC), and voltage-dependent calcium channel (VDCC) first appear in Porifera. Substance-P receptor 1 (TACR1) emerged from Coelenterata. Somatostatin receptor type 2 (SSTR2), TRPV1 and voltage-dependent sodium channels (VDSC) appear in Platyhelminthes. Calcitonin gene-related peptide receptor (CGRPR) was first identified in Nematoda. However, opioid receptors (OPRs) and most NPs were discovered only in vertebrates and exist from agnatha to humans. The results demonstrated that homologs of nociception and pain-related ICs exist from lower animal phyla to high animal phyla, and that most of the GPCRs originate from low to high phyla sequentially, whereas OPRs and NPs are newly evolved in vertebrates, which provides hints of the evolution of nociception and pain-related proteins in animals and humans.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"19 ","pages":"11769343231216914"},"PeriodicalIF":2.6,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138812717","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}
Ibrahim H Eissa, Reda G Yousef, Eslam B Elkaeed, Aisha A Alsfouk, Dalal Z Husein, Ibrahim M Ibrahim, Hesham A El-Mahdy, Hazem Elkady, Ahmed M Metwaly
{"title":"Computer-Assisted Drug Discovery of a Novel Theobromine Derivative as an EGFR Protein-Targeted Apoptosis Inducer.","authors":"Ibrahim H Eissa, Reda G Yousef, Eslam B Elkaeed, Aisha A Alsfouk, Dalal Z Husein, Ibrahim M Ibrahim, Hesham A El-Mahdy, Hazem Elkady, Ahmed M Metwaly","doi":"10.1177/11769343231217916","DOIUrl":"10.1177/11769343231217916","url":null,"abstract":"<p><p>The overexpression of the Epidermal Growth Factor Receptor (EGFR) marks it as a pivotal target in cancer treatment, with the aim of reducing its proliferation and inducing apoptosis. This study aimed at the CADD of a new apoptotic EGFR inhibitor. The natural alkaloid, theobromine, was used as a starting point to obtain a new semisynthetic (di-ortho-chloro acetamide) derivative (<b>T-1-DOCA</b>). Firstly, <b>T-1-DOCA</b>'s total electron density, energy gap, reactivity indices, and electrostatic surface potential were determined by DFT calculations, Then, molecular docking studies were carried out to predict the potential of <b>T-1-DOCA</b> against wild and mutant EGFR proteins. <b>T-1-DOCA</b>'s correct binding was further confirmed by molecular dynamics (MD) over 100 ns, MM-GPSA, and PLIP experiments. In vitro, <b>T-1-DOCA</b> showed noticeable efficacy compared to erlotinib by suppressing EGFR<sup>WT</sup> and EGFR<sup>T790M</sup> with IC<sub>50</sub> values of 56.94 and 269.01 nM, respectively. <b>T-1-DOCA</b> inhibited also the proliferation of H1975 and HCT-116 malignant cell lines, exhibiting IC<sub>50</sub> values of 14.12 and 23.39 µM, with selectivity indices of 6.8 and 4.1, respectively, indicating its anticancer potential and general safety. The apoptotic effects of <b>T-1-DOCA</b> were indicated by flow cytometric analysis and were further confirmed through its potential to increase the levels of BAX, Casp3, and Casp9, and decrease Bcl-2 levels. In conclusion, <b>T-1-DOCA</b>, a new apoptotic EGFR inhibitor, was designed and evaluated both computationally and experimentally. The results suggest that <b>T-1-DOCA</b> is a promising candidate for further development as an anti-cancer drug.</p>","PeriodicalId":50472,"journal":{"name":"Evolutionary Bioinformatics","volume":"19 ","pages":"11769343231217916"},"PeriodicalIF":1.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479082","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}