Frontiers in bioinformatics最新文献

{"title":"Primer on machine learning applications in brain immunology.","authors":"Niklas Binder, Ashkan Khavaran, Roman Sankowski","doi":"10.3389/fbinf.2025.1554010","DOIUrl":"https://doi.org/10.3389/fbinf.2025.1554010","url":null,"abstract":"<p><p>Single-cell and spatial technologies have transformed our understanding of brain immunology, providing unprecedented insights into immune cell heterogeneity and spatial organisation within the central nervous system. These methods have uncovered complex cellular interactions, rare cell populations, and the dynamic immune landscape in neurological disorders. This review highlights recent advances in single-cell \"omics\" data analysis and discusses their applicability for brain immunology. Traditional statistical techniques, adapted for single-cell omics, have been crucial in categorizing cell types and identifying gene signatures, overcoming challenges posed by increasingly complex datasets. We explore how machine learning, particularly deep learning methods like autoencoders and graph neural networks, is addressing these challenges by enhancing dimensionality reduction, data integration, and feature extraction. Newly developed foundation models present exciting opportunities for uncovering gene expression programs and predicting genetic perturbations. Focusing on brain development, we demonstrate how single-cell analyses have resolved immune cell heterogeneity, identified temporal maturation trajectories, and uncovered potential therapeutic links to various pathologies, including brain malignancies and neurodegeneration. The integration of single-cell and spatial omics has elucidated the intricate cellular interplay within the developing brain. This mini-review is intended for wet lab biologists at all career stages, offering a concise overview of the evolving landscape of single-cell omics in the age of widely available artificial intelligence.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"5 ","pages":"1554010"},"PeriodicalIF":2.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060334","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":"Genomic analysis of <i>Listeria monocytogenes</i> strains from dairy products in Ethiopia.","authors":"Mebrie Zemene Kinde, Bizuayehu Kerisew, Tegegne Eshetu, Abebe Tesfaye Gessese","doi":"10.3389/fbinf.2025.1572241","DOIUrl":"https://doi.org/10.3389/fbinf.2025.1572241","url":null,"abstract":"<p><p>This study explored virulence genes, antibiotic resistance genes, and mobile genetic elements in 14 <i>Listeria monocytogenes</i> strains from milk and dairy products collected from different regions of Ethiopia. The strains were classified into two Multilocus Sequence Typing sequence types (ST2 and ST45) and further grouped into clonal complexes (CC2) and different cgMLST types. Twenty-nine virulence genes were identified across all 14 strains, with <i>lplA1</i> detected at higher levels in all strains except SAMN28661660. All <i>L. monocytogenes</i> strains also carried four antibiotic resistance genes (<i>fosX</i>, <i>lin</i>, <i>norB</i>, <i>mprF</i>), contributing to their ability to withstand multiple antimicrobial agents. Notably, no plasmids or mobile genetic elements were detected. Stress resistance genes, including <i>stress survival islet 1</i> (<i>SSI1_lmo0447</i>), <i>lmo 1800</i>, and <i>lmo1799</i>, were identified in all strains. However, genes encoding for disinfectant resistance were not identified from all strains. LGI-2 was found in all the strains and none of the studied strains harbored LGI-1 and LGI-3. Conserved CRISPR-Cas systems were found in some strains. KEGG pathway analysis revealed that <i>inlA</i> and <i>inlB</i> genes facilitate bacterial internalization through host actin polymerization. Overall, the study provided crucial insights into the genomic features of <i>L. monocytogenes</i> in the Ethiopian dairy chain. It is crucial to establish continuous monitoring of <i>L. monocytogenes</i> in dairy products, improve sanitation, enforce stricter antibiotic usage and food safety regulations, and raise public awareness of associated risks.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"5 ","pages":"1572241"},"PeriodicalIF":2.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993733","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":"Identification of novel drug targets and small molecule discovery for MRSA infections.","authors":"Nandha Kumar Subramani, Subhashree Venugopal","doi":"10.3389/fbinf.2025.1562596","DOIUrl":"https://doi.org/10.3389/fbinf.2025.1562596","url":null,"abstract":"<p><strong>Introduction: </strong>The topmost deadliest microorganism, namely, methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), causes dreadful infections like bacteremia, pneumonia, endocarditis, and systemic inflammations. The virulence factors associated with MRSA exhibit multidrug-resistant characteristics, complicating treatment choices. So, the primary objective of this study is to identify the MRSA virulence factors and inhibiting its activity utilizing bioinformatic approaches.</p><p><strong>Methods: </strong>The screening of novel therapeutic MRSA targets was conducted based on the predictions retrieved from non-homologous, physicochemical analysis, subcellular localization, druggability, and virulence factor examinations. Following that, flavonoid compounds were docked against specific MRSA targets using AutoDock Vina. Further, molecular dynamic simulations and binding free energy calculations were performed using simulation software.</p><p><strong>Results: </strong>After examining 2,640 virulence factors that presented in MRSA, the heme response regulator R (HssR) was found to be a novel protein that greatly controls the levels of heme in MRSA infections. Subsequently, the binding energy calculations for flavonoid compounds and HssR revealed that the catechin provided -7.9 kcal/mol, which surpassed the standard drug, namely, vancomycin (-5.9 kcal/mol). Further, the results were validated by evaluating molecular dynamic simulation parameters like RMSD, RMSF, ROG, SASA, and PCA. Through analyzing these parameters, catechin provided a more stable, compact nature and less solvent exposure with HssR than vancomycin. Moreover, the predicted binding free energy for HssR-catechin was found to be -23.0 kcal/mol, which was less compared to the HssR-vancomycin (-16.91 kcal/mol) complex. The results suggested that the catechin was able to modulate the activity of the HssR protein effectively.</p><p><strong>Conclusion: </strong>These potential findings revealed that heme response regulator R as a promising therapeutic target while the flavonoid compound catechin could act as alternative therapeutic inhibitor that target MRSA infections.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"5 ","pages":"1562596"},"PeriodicalIF":2.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051927","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":"Using AlphaFold-Multimer to study novel protein-protein interactions of predation essential hypothetical proteins in <i>Bdellovibrio</i>.","authors":"Ibukun John Abulude, Isabel Cristina Rodríguez Luna, Alejandro Sánchez Varela, Andrew Camilli, Daniel E Kadouri, Xianwu Guo","doi":"10.3389/fbinf.2025.1566486","DOIUrl":"https://doi.org/10.3389/fbinf.2025.1566486","url":null,"abstract":"<p><p>Bdellovibrio <i>bacteriovorus</i> is the most studied member of a group of small motile Gram-negative bacteria called <i>Bdellovibrio</i> and Like Organisms (BALOs). <i>B. bacteriovorus</i> can prey on Gram-negative bacteria, including multi-drug resistant pathogens, and has been proposed as an alternative to antibiotics. Although the life cycle of <i>B. bacteriovorus</i> is well characterized, some molecular aspects of <i>B. bacteriovorus</i>-prey interaction are poorly understood. Hypothetical proteins with unestablished functions have been implicated in <i>B. bacteriovorus</i> predation by many studies. Our approach to characterize these proteins employing Alphafold has revealed novel interactions among attack phase-hypothetical proteins, which may be involved in less understood mechanisms of the <i>Bdellovibrio</i> attack phase. Here, we overlapped attack phase genes from <i>B. bacteriovorus</i> transcriptomic data sets and from transposon sequencing data sets to generate a set of proteins that are both expressed at the attack phase and are necessary for predation, which we termed Attack Phase Predation-Essential Proteins (AP-PEP). By applying Markov Cluster Algorithm and AlphaFold-Multimer to analyze the protein network and interaction partners of the AP-PEPs, we predicted high-confidence protein-protein interactions and two structurally similar but unique novel protein complexes formed among proteins of the Bd2209-Bd2212 and Bd2723-Bd2726 operons. Furthermore, we confirmed the interaction between hypothetical proteins Bd0075 and Bd0474 using the Bacteria Adenylate Cyclase Two-Hybrid system. In addition, we confirmed that the C-terminal domain of Bd0075, which contains Tetratricopeptide repeat motifs, participates principally in its interaction with Bd0474. This study revealed previously unknown cooperation among predation essential hypothetical proteins in the attack phase <i>B. bacteriovorus</i> and has paved the way for further work to understand molecular mechanisms of BALO predation processes.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"5 ","pages":"1566486"},"PeriodicalIF":2.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061229","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":"Transcripts derived from AmnSINE1 repetitive sequences are depleted in the cortex of autism spectrum disorder patients.","authors":"Nicolina Sciaraffa, Daniele Santoni, Andrea Li Greci, Swonild Ilenia Genovese, Claudia Coronnello, Walter Arancio","doi":"10.3389/fbinf.2025.1532981","DOIUrl":"https://doi.org/10.3389/fbinf.2025.1532981","url":null,"abstract":"<p><strong>Aims: </strong>Autism spectrum disorder (ASD) is a brain developmental disability with a not-fully clarified etiogenesis. Current ASD research largely focuses on coding regions of the genome, but up to date much less is known about the contribution of non-coding elements to ASD risk. The non-coding genome is largely made of DNA repetitive sequences (RS). Although RS were considered slightly more than \"junk DNA\", today RS have a recognized role in almost every aspect of human biology, especially in developing human brain. Our aim was to test if RS transcription may play a role in ASD.</p><p><strong>Methods: </strong>Global RS transcription was firstly investigated in <i>postmortem</i> dorsolateral prefrontal cortex of 13 ASD patients and 39 matched controls. Results were validated in independent datasets.</p><p><strong>Results: </strong>AmnSINE1 was the only RS significantly downregulated in ASD specimens. The role of AmnSINE1 in ASD has been investigated at multiple levels, showing that the 1,416 genes containing AmnSINE1 are associated with nervous system development and autism susceptibility. This has been confirmed in a different experimental setting, such as in organoid models of the human cerebral cortex, harboring different ASD causative mutations. AmnSINE1 related genes are transcriptionally co-regulated and are involved not only in brain formation but can specifically be involved in ASD development. Looking for a possible direct role of AmnSINE1 non-coding transcripts in ASD, we report that AmnSINE1 transcripts may alter the miRNA regulatory landscape for genes involved in neurogenesis.</p><p><strong>Conclusion: </strong>Our findings provide preliminary evidence supporting a role for AmnSINE1 in ASD development.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"5 ","pages":"1532981"},"PeriodicalIF":2.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999522","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":"A cost and community perspective on the barriers to microbiome data reuse.","authors":"Julia M Kelliher, Leah Y D Johnson, Francisca E Rodriguez, Jaclyn K Saunders, Marie E Kroeger, Buck Hanson, Aaron J Robinson, Winston E Anthony, Marc W Van Goethem, Anders Kiledal, Ahmed A Shibl, Amanda Araujo Serrao de Andrade, Cassandra L Ettinger, Chhedi Lal Gupta, Chris R P Robinson, Cristal Zuniga, Daniel Sprockett, Douglas Terra Machado, Emilie J Skoog, Iyanu Oduwole, Jason A Rothman, Kaelan Prime, Katherine R Lane, Leandro Nascimento Lemos, Lisa Karstens, Mark McCauley, Mitiku Mihiret Seyoum, Moamen M Elmassry, Mustafa Guzel, Reid Longley, Simon Roux, Thomas M Pitot, Emiley A Eloe-Fadrosh","doi":"10.3389/fbinf.2025.1585717","DOIUrl":"https://doi.org/10.3389/fbinf.2025.1585717","url":null,"abstract":"<p><p>Microbiome research is becoming a mature field with a wealth of data amassed from diverse ecosystems, yet the ability to fully leverage multi-omics data for reuse remains challenging. To provide a view into researchers' behavior and attitudes towards data reuse, we surveyed over 700 microbiome researchers to evaluate data sharing and reuse challenges. We found that many researchers are impeded by difficulties with metadata records, challenges with processing and bioinformatics, and problems with data repository submissions. We also explored the cost constraints of data reuse at each step of the data reuse process to better understand \"pain points\" and to provide a more quantitative perspective from sixteen active researchers. The bioinformatics and data processing step was estimated to be the most time consuming, which aligns with some of the most frequently reported challenges from the community survey. From these two approaches, we present evidence-based recommendations for how to address data sharing and reuse challenges with concrete actions for future work.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"5 ","pages":"1585717"},"PeriodicalIF":2.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043965","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":"Harnessing computational immunology to design targeted subunit vaccines for infectious bursal disease in poultry.","authors":"Elijah Kolawole Oladipo, Stephen Feranmi Adeyemo, Ayomiposi Isaiah Oshoneye, Hannah Blessing Akintola, Bolatito Islam Elegbede, Tobiloba Uren Ayoomoba, Dorcas Ayomide Atilade, Omolara Omoboye Adegboye, Abuoma Elizabeth Ejikeme, Chris Olamide Balogun, Kehinde Abolade Aderibigbe, Possible Okikiola Popoola, Victoria Ajike Alabi, Boluwatife Ayobami Irewolede, Gbemi Henry Ano-Edward, Ademola Olabode Ayeleso, Helen Onyeaka","doi":"10.3389/fbinf.2025.1562997","DOIUrl":"https://doi.org/10.3389/fbinf.2025.1562997","url":null,"abstract":"<p><strong>Introduction: </strong>Infectious bursal disease (IBD), caused by the infectious bursal disease Q8 virus (IBDV), is a highly contagious disease in young chickens, leading to immunosuppression with great economic importance. IBDV, a non-enveloped virus with a bipartite dsRNA genome, infects the bursa of Fabricius, causing severe gastrointestinal disease. Effective vaccines are urgently needed due to the limitations of current oral vaccines, including gastrointestinal degradation and low immunogenicity. This study designs and evaluates a multiepitope subunit vaccine using immunoinformatics.</p><p><strong>Methods: </strong>Sequences of the IBDV structural proteins VP2 and VP3 were obtained from the National Centre for Biotechnology Information) NCBI. These are structural proteins VP2 and VP3 were subjected to the Vaxijen 2.0 webserver to predict the antigenicity, ToxiPred to predict the toxicity and further analyzed to identify immunogenic epitopes of Chicken Leukocyte Antigens (CLAs) using the NetMHCpan 4.1 webserver.</p><p><strong>Results: </strong>The final vaccine construct includes 2 HTL, 21 CTL, and 7 LBL epitopes, with gallinacin-3 precursor as an adjuvant. The construct is antigenic (0.5605), non-allergenic, and non-toxic, consisting of 494 amino acids with a molecular weight of 54.88 kDa and a positive charge (pI of 9.23). It is stable, hydrophilic, and soluble. Population coverage analysis revealed a global immune coverage of 89.83%, with the highest in Europe (99.86%) and the lowest in Central America (25.01%). Molecular docking revealed strong interactions with TLR-2_1, TLR-4, and TLR-7, with TLR-7 exhibiting the highest binding affinity (-366.15 kcal/mol). Immune simulations indicated a robust immune response, with high initial IgM levels, sustained IgG, memory cell formation, and activation of T helper (Th) cells 1 and 2, Natural Killer (NK) cells, and dendritic cells, suggesting potential long-lasting immunity against IBDV.</p><p><strong>Discussion: </strong>This study presents a promising multi-epitope subunit vaccine candidate capable of effective immunization against IBDV with broad population coverage. However, further <i>in vivo</i> experimental validation is required to confirm its efficacy and safety.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"5 ","pages":"1562997"},"PeriodicalIF":2.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013487","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":"Identification of key hub genes in pancreatic ductal adenocarcinoma: an integrative bioinformatics study.","authors":"Kankana Bhattacharjee, Avik Sengupta, Rahul Kumar, Aryya Ghosh","doi":"10.3389/fbinf.2025.1536783","DOIUrl":"https://doi.org/10.3389/fbinf.2025.1536783","url":null,"abstract":"<p><p>Pancreatic Ductal Adenocarcinoma (PDAC) poses a significant health threat characterized by poor clinical outcomes, largely attributable to late detection, chemotherapy resistance, and the absence of tailored therapies. Despite progress in surgical, radiation, and chemotherapy treatments, 80% of PDAC patients do not benefit optimally from systemic therapy, often due to asymptomatic presentation or disease regression upon diagnosis. The disease's progression is influenced by complex interactions involving immunological, genetic, and environmental factors, among others. However, the precise molecular mechanisms underlying PDAC remain incompletely understood. A major challenge in elucidating PDAC's origins lies in deciphering the genetic variations governing its network. PDAC exhibits heterogeneity, manifesting diverse genetic compositions, cellular attributes, and behaviors across patients and within tumors. This diversity complicates diagnosis, treatment strategies, and prognostication. Identification of \"Differentially Expressed Genes\" (DEGs) between PDAC and healthy controls is vital for addressing these challenges. These DEGs serve as the foundation for constructing the PDAC protein interaction network, with their network properties being assessed for further insights. Our analysis revealed five key hub genes (KHGs): <i>EGF, SRC, SDC1, ICAM1 and CEACAM5</i>. The KHGs were predominantly enriched in pathways such as: ErbB signaling pathway, Rap1 signaling pathway, etc. Acknowledging the therapeutic promise and biomarker importance of PDAC KHGs, we have also pinpointed approved medications for the identified key genes. Nevertheless, it is crucial to conduct experimental validation on KHGs to confirm their effectiveness within the PDAC context. Overall, this study identified potential key hub genes implicated in the progression of PDAC, offering significant guidance for personalized clinical decision-making and molecular-targeted therapy for PDAC patients.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"5 ","pages":"1536783"},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054677","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":"Inhibition potential of margolonone and isomargolonone against the dengue virus protease using molecular modeling approaches.","authors":"Gourav Choudhir, Faiza Iram, Israil, Mohammad Shahid, Anas Shamsi, Md Imtaiyaz Hassan, Asimul Islam","doi":"10.3389/fbinf.2025.1517115","DOIUrl":"https://doi.org/10.3389/fbinf.2025.1517115","url":null,"abstract":"<p><strong>Background: </strong>Dengue is a mosquito-borne viral disease with no cure. Inhibiting key enzymes vital in replication could manage the dengue virus infection. This study investigated the potential of margolonone and isomargolonone from <i>Azadirachta indica</i> to inhibit dengue virus replication.</p><p><strong>Methods: </strong>The 3D structure of margolonone and isomargolonone were obtained from the PubChem database. The drug-likeness properties of these molecules were performed using a Swiss-ADME server. The molecular docking and molecular dynamics simulation assessed binding affinity and interactions.</p><p><strong>Results: </strong>The drug-likeness of parameters showed that Margolonone and isoMargolonone showed zero violation of Lipinski rules. Docking simulations showed that both compounds bind to the active site of a critical enzyme (NS3 protease) essential for viral replication. Molecular dynamics simulations suggested that isomargolonone may bind more stably to NS3 than margolonone. Additionally, MMPBSA analysis showed that Margolonone does not show favorable binding energy.</p><p><strong>Conclusion: </strong>These findings warrant further investigation of isomargolonone as a potential anti-dengue drug. Further <i>in-vitro</i> and <i>in-vivo</i> evaluations need to be done before accepting it as drug molecules.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"5 ","pages":"1517115"},"PeriodicalIF":2.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060738","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":"Comprehensive structural and functional analyses of RAD50 nsSNPs: from prediction to impact assessment.","authors":"Samina Malik, Mirza Jawad Ul Hasnain, Gul Zaib, Haleema Saadia, Arif Malik, Ayesha Zahid","doi":"10.3389/fbinf.2025.1535482","DOIUrl":"https://doi.org/10.3389/fbinf.2025.1535482","url":null,"abstract":"<p><strong>Background: </strong>The RAD50 gene on chromosome 5q3.11 plays an important role in the MRN (Mre11-Rad50-Nbs1) complex. This complex orchestrates cellular responses to the DNA double-strand breaks (DSBs) through several pathways for genome stability. This study aims to investigate the functional impact of non-synonymous single-nucleotide polymorphisms (nsSNPs) in RAD50 (a breast cancer-associated gene) and focuses on their consequences on protein structure and interaction within the MRN complex.</p><p><strong>Methods: </strong>A total of 1,806 nsSNPs were retrieved and subjected to variant analysis using a set of computational tools and ConSurf. Pathogenicity and protein stability criteria were established based on specific tools. Highly conserved damaging nsSNPs were prioritized for the structural analysis. GOR-IV was used for secondary structure prediction, whereas AlphaFold, RoseTTAFold, and I-TASSER were used for protein structure prediction. The docking of RAD50-Mre11A complexes was performed using HADDOCK to assess the impact of nsSNPs on protein-protein interactions. Molecular dynamic simulation was performed to verify the role of mutants in molecular docking analysis.</p><p><strong>Results: </strong>A subset of pathogenic and disease-associated nsSNPs in the RAD50 gene altered the protein stability and interactions with the Mre11A protein. Substantial alterations in the interacting profiles of mutants (A73P, V117F, L518P, L1092R, N1144S, and A1209T) suggest potential implications for DNA repair mechanisms and genome stability.</p><p><strong>Conclusion: </strong>The study discloses the normative impact of RAD50 mutations on the pathophysiology of breast cancer. It can provide the basis to treat RAD50 mutation-deficient cells.</p>","PeriodicalId":73066,"journal":{"name":"Frontiers in bioinformatics","volume":"5 ","pages":"1535482"},"PeriodicalIF":2.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028378","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}