Genomics & informatics最新文献

{"title":"Recovering CDR3 sequences from RNA-seq data: a critical assessment of computational and experimental strategies.","authors":"Mandana AmeliMojarad, Melika AmeliMojarad","doi":"10.1186/s44342-026-00084-5","DOIUrl":"10.1186/s44342-026-00084-5","url":null,"abstract":"<p><p>The adaptive immune response depends on T cell receptor (TCR) diversity to counter cancers, autoimmunity, and infections. This diversity is encoded within CDR3, which serves as a unique barcode for each T cell clone. Characterizing CDR3 sequences is essential for tracking clonal dynamics, identifying neoantigen-reactive T cells, and designing personalized immunotherapy. While TCR-seq remains the benchmark, existing RNA-seq datasets offer a cost-effective retrospective alternative. However, tools like MiXCR and TRUST4, optimized for TCR-enriched samples, are limited in bulk and single-cell RNA-seq due to low transcript abundance and sparse coverage. In this review, we synthesize quantitative evidence from published head-to-head benchmarking studies that performed matched RNA-seq and TCR-seq on the same biological samples. These studies demonstrate that standard RNA-seq typically recovers only 3-5% of unique clonotypes identified by TCR-seq, with substantial underrepresentation of low-frequency clones; however, in T cell-rich tissues and when high sequencing depth is combined with optimized computational pipelines, RNA-seq can capture the majority of high-frequency clonotypes, albeit with limited accuracy in clonotype frequency estimation and poor α/β pairing recovery. We review computational efforts to recover CDR3 sequences from RNA-seq data, highlighting recurrent obstacles: transcript scarcity, fragmentation, short reads, and assembly errors. We critically assess whether artificial intelligence can overcome these barriers. We also examine emerging wet-lab strategies including probe-based enrichment, FUME-TCRseq, and rhTCRseq. We conclude that RNA-seq cannot replace TCR-seq, but AI-enhanced tools with targeted library improvements could expand the utility of existing datasets and degraded specimens.</p>","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225725","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":"The reference shapes the signal: chrX genotype summaries and classifier sex disparity between GRCh38 and T2T-CHM13 callsets.","authors":"R Craig Stillwell","doi":"10.1186/s44342-026-00083-6","DOIUrl":"10.1186/s44342-026-00083-6","url":null,"abstract":"<p><p>Laboratories that move from GRCh38 to T2T-CHM13 take on a new callset as well as a new assembly. I asked whether the move changes sex-chromosome genotype summaries, and whether it changes how well classifiers trained on those summaries serve males and females. I compared the published 1000 Genomes GRCh38 and T2T-CHM13 callsets for 3,202 people. The two callsets come from different alignment, calling, phasing and filtering workflows, so every difference below belongs to the reference and its pipeline together. In women, the fraction of non-reference chrX genotypes that were heterozygous was 0.605 on GRCh38 and 0.644 on T2T. It fell in African-ancestry women and rose in the other four superpopulations. The rise came from fewer non-reference homozygous genotypes (- 7,757 per woman) and not from more heterozygous ones (- 1,504). Five classifier families were trained on six chrX summaries to predict superpopulation, and the male-female gap in balanced accuracy was compared between callsets. Women were classified better than men under both callsets. Logistic regression, random forest and XGBoost widened that gap on T2T, and the support vector machine and the perceptron narrowed it. After correction across all 20 tests, random forest, XGBoost and the support vector machine remained significant. Separating relatives did not remove the disagreement. Classifiers built from the first 500 common SNPs per chromosome in file order showed no change after correction. The gap measures model performance, not biological sex bias. Resolving the assembly from its callset requires processing the same reads through one pipeline against both references.</p>","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208442","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":"Impact of extended fertilization on soil microbial diversity: a comparative full-length 16S rRNA amplicon analysis.","authors":"Kazi Chamonara, Md Habib Ullah Masum, Fahmida Ferdous Faria, Salma Chowdhury, Md Sadequr Rahman Khan, Md Abul Kashem","doi":"10.1186/s44342-026-00078-3","DOIUrl":"https://doi.org/10.1186/s44342-026-00078-3","url":null,"abstract":"<p><strong>Background: </strong>Soil bacterial communities are essential for regulating soil fertility, nutrient cycling, and agricultural sustainability. However, their responses to different fertilization regimes, especially in intensively managed agroecosystems, remain inadequately characterized in Chattogram.</p><p><strong>Methods: </strong>This study assessed the effects of prolong applications of chemical and organic fertilizers on soil bacterial community structure using culture-independent techniques (Oxford Nanopore long-read 16S rRNA gene sequencing).</p><p><strong>Result: </strong>In subsequent taxonomic composition analyses, beta diversity revealed significant differences in bacterial community composition among the fertilization regimes (p < 0.05), suggesting that long-term differences in fertilization practices may be associated with variation in bacterial community structure. The R² value (0.84) indicates that the fertilization regime was associated with a substantial proportion of the observed variation in bacterial community composition. However, organic amendment was associated with significantly higher abundances of several bacterial taxa linked to plant growth promotion and nutrient cycling than chemical fertilization. Among the predominant taxa, Bacillus was represented by 8.44 ± 1.255% under chemical fertilization and 14.77 ± 0.790% under organic amendment, while Gemmataceae accounted for 7.65 ± 0.689% and 11.60 ± 0.441%, respectively. A similar upward trend was observed among the less abundant taxa, with Xanthobacteraceae comprising 2.88 ± 0.197% and 4.15 ± 0.204%, and Tumebacillus 1.35 ± 0.171% and 2.73 ± 0.183%, under chemical fertilization and organic amendment, respectively (FDR < 0.001). Bradyrhizobium and Paenibacillus showed relatively similar abundances between the two fertilization treatments. Bradyrhizobium accounted for 3.33 ± 0.240% under chemical fertilization and 2.90 ± 0.216% under organic amendment (FDR = 0.055), whereas Paenibacillus represented 2.02 ± 0.173% and 2.50 ± 0.155%, respectively (FDR < 0.001). METAGENassist predictions and multivariate functional profiling suggest that organic amendments may enhance microbial capacity for the decomposition of organic matter and nutrient turnover.</p><p><strong>Conclusion: </strong>These current findings suggest that the effects of fertilization on soil bacterial communities may extend beyond overall richness and may involve changes in community structure and relative abundance. However, the effects of fertilization on soil fertility and long-term agricultural sustainability should be assessed in the context of broader soil attributes and microbial community features.</p>","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187248","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":"Design and in silico evaluation of PV-GNProtecta: an mRNA multi-epitope vaccine candidate against Puumala virus using immunoinformatics and structural analysis.","authors":"Tanvir Hossain, Abdullah Al Mahmud, Maisha Afrin, Sakibur Rahman, Shaheda Siddiqa Tahia, Ahmad Abdullah Mahdeen, Md Habib Ullah Masum","doi":"10.1186/s44342-026-00081-8","DOIUrl":"10.1186/s44342-026-00081-8","url":null,"abstract":"<p><p>Puumala virus (PUUV), the principal causative agent of nephropathia epidemica (NE), poses a significant public health threat due to its zoonotic transmission, renal complications, and the lack of an approved vaccine. In this study, an immunoinformatics-driven mRNA multi-epitope vaccine, PV-GNProtecta, was designed using conserved regions of the viral glycoprotein (G) and nucleoprotein (N). Highly antigenic, non-allergenic, and non-toxic T-cell and B-cell epitopes were identified and assembled with appropriate adjuvants to enhance immunogenicity. Population coverage analysis suggested broad HLA responsiveness across diverse populations. The vaccine construct exhibited favorable physicochemical properties, including stability, solubility, and antigenicity. Structural validation predicted high model quality, with 95.5% of residues located in favored Ramachandran regions and an ERRAT score of 91.4. Molecular docking and MM-GBSA analyses predicted favorable computational interactions between PV-GNProtecta and TLR4, while a 100 ns molecular dynamics simulation provided computational insights into the dynamic behavior of the vaccine-TLR4 complex. Codon optimization suggested compatibility of the designed sequence with an Escherichia coli-based expression framework. Immune simulation predicted potential humoral and cellular immune response patterns, including changes in IgG, IFN-γ, and IL-2 levels. The designed mRNA sequence exhibited favorable predicted secondary structural characteristics; however, further experimental evaluation is required to assess translational efficiency and stability. Although this study is limited to computational analyses and requires experimental validation, the findings suggest that PV-GNProtecta may represent a potential candidate for further investigation against PUUV infection.</p>","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169140","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":"The risk of over-interpreting in silico predictions as clinical evidence: a comment on Roy et al. (2024).","authors":"Dimitri Tchernitchko","doi":"10.1186/s44342-026-00082-7","DOIUrl":"10.1186/s44342-026-00082-7","url":null,"abstract":"<p><p>Roy et al. reported an extensive computational analysis of nonsynonymous single-nucleotide variants (nsSNPs) in the human CYLD gene and characterized several variants as potentially disease- or cancer-associated. Although such analyses can be valuable for generating hypotheses, computational predictions should be clearly distinguished from clinical or functional evidence. Among the 18 \"high-risk nsSNPs\" prioritized by the authors, only p.Glu747Gly (E747G) has established clinical evidence supporting pathogenicity, whereas the remaining variants lack sufficient evidence for pathogenic classification and should be considered variants of uncertain significance pending further evidence. We highlight three major concerns: the lack of independence among some prediction tools used for variant prioritization; the interpretation of somatic mutation clustering as evidence for germline disease association; and the presentation of variants with no established clinical or experimental evidence as disease-associated. Under the ACMG/AMP framework, computational evidence can provide supporting evidence but cannot substitute for clinical, population, segregation, or functional evidence. We suggest that the terminology and conclusions of the original article be revised to distinguish computationally predicted effects from demonstrated disease associations.</p>","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140059","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":"In silico structural and functional characterisation of two hypothetical proteins from the plant‑associated bacterium Kosakonia cowanii F52.","authors":"Md Zahirul Islam, Md Jahid Hasan Dewan, Abdul Baess Keyhani, Monira Fayaz","doi":"10.1186/s44342-026-00080-9","DOIUrl":"https://doi.org/10.1186/s44342-026-00080-9","url":null,"abstract":"<p><p>Kosakonia cowanii promotes plant growth under salt stress, but many of its hypothetical proteins (HPs) remain uncharacterised. We screened 218 HPs from K. cowanii F52 using sequential filters for physicochemical stability, subcellular localisation, and conserved domains. Four candidates were modelled with AlphaFold2 and validated by stereochemical and global geometry scores. Two HPs, MHQ1860809.1 and MHQ1862734.1, were selected based on combined global and per-residue model-quality metrics for further functional annotation via structural similarity searches, Gene Ontology (GO), and KEGG pathway analysis. Molecular docking of NAD⁺ was subsequently performed on MHQ1860809.1 to evaluate cofactor binding. MHQ1860809.1 is predicted to adopt a canonical Rossmann fold with a conserved NAD(P)-binding pocket; docking was consistent with NAD⁺ binding (Vina score -7.8 kcal/mol). GO predicted oxidoreductase activity (GO:0016646) and proline metabolic process (GO:0006560). MHQ1862734.1 is predicted to fold into an ARM-repeat superhelix, lacks any ligand-binding cavity, and is structurally similar to importin-β and AP-2 adaptor subunits. However, no EC numbers or KEGG orthologies could be assigned. MHQ1860809.1 is therefore structurally consistent with a putative NAD(P)-dependent oxidoreductase potentially involved in proline biosynthesis, whereas MHQ1862734.1 adopts an ARM-repeat fold of unknown function. These findings generate specific, testable hypotheses and provide a foundation for future experimental work on the molecular basis of K. cowanii plant growth-promoting activity.</p>","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121186","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 systems biology network analysis of root resorption biomarkers and their clinical relevance in orthodontics: a pilot study.","authors":"Parzhin Moradi, Vahid Mollabashi, Amir Taherkhani, Homa Farhadifard, Erfan Ayubi","doi":"10.1186/s44342-026-00079-2","DOIUrl":"10.1186/s44342-026-00079-2","url":null,"abstract":"<p><strong>Background: </strong>External apical root resorption is a frequently reported iatrogenic consequence of orthodontic tooth movement. This pilot study used an integrated systems biology approach to identify signaling pathways, key genes, and candidate salivary biomarkers associated with orthodontic root resorption to support future functional research.</p><p><strong>Methods: </strong>The present study used a sequential workflow that began with identifying root resorption-associated genes from a systematic literature review and the DisGeNET database. Subsequently, a protein-protein interaction (PPI) network was constructed to identify hub genes, followed by pathway enrichment and Gene Ontology analyses. Next, a Gene Regulatory Network was built to predict upstream transcription factors. Finally, an ELISA assay was performed on saliva samples from 12 patients with orthodontic root resorption and 12 matched controls to validate the computational findings experimentally. The diagnostic utility of the selected markers was assessed using receiver operating characteristic (ROC) curves.</p><p><strong>Results: </strong>A set of 160 genes was found to be linked to the process of orthodontic root resorption. Within the PPIN, 13 genes were recognized as central hub genes. Among these, CASP1 and SPP1 were selected for the ELISA assay. Gene Regulatory Network analysis computationally identified IRF4 as the most impactful upstream regulator of CASP1 and SPP1. The ELISA analysis confirmed overexpression of salivary Caspase-1 and Osteopontin proteins in patients with orthodontic root resorption compared with those without signs of the condition. Caspase-1 emerged as a strong candidate for non-invasive diagnosis of root resorption in orthodontic patients, with impressive efficacy (AUC = 0.9861; Youden Index = 0.917).</p><p><strong>Conclusion: </strong>This study suggests that elevated salivary levels of CASP1 and SPP1 are associated with radiographically confirmed OIIRR. These proteins represent candidate biomarkers whose potential biological relevance warrants longitudinal evaluation, rather than definitive predictive tools or therapeutic targets. Therefore, given the preliminary nature of these bioinformatics analyses and the limited sample size in the clinical validation, further large-scale prospective studies are required to confirm their diagnostic and therapeutic utility.</p>","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077260","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":"Pre-sampling conditions affect salivary genomic DNA yield and human DNA fraction: a single-donor pilot study.","authors":"Sangsoo Park, Hyoungjin Choi, Jong Bhak","doi":"10.1186/s44342-026-00077-4","DOIUrl":"10.1186/s44342-026-00077-4","url":null,"abstract":"<p><p>As saliva-based genomic analyses expand, the effect of common pre-sampling behaviors on salivary genomic DNA (gDNA) recovery remains poorly characterized. In this single-donor pilot study, we tested eight pre-sampling conditions combining tooth brushing, gargling, and water intake. Saliva was collected in triplicate under each condition, cells were isolated, and gDNA was extracted using the Qiagen Kit. Three-way ANOVA showed that brushing was the dominant factor, accounting for 62.9% of total variation in DNA yield. Gargling had a smaller but significant effect (5.6%), while water intake had no significant effect. DNA purity, assessed by A260/280 ratio, remained stable across all conditions. To assess the human-to-bacterial DNA ratio, we performed qPCR using RPPH1 (human) and 16S rRNA (bacterial) markers. Brushing increased the human DNA fraction but reduced the absolute amount of human DNA recovered, indicating a purity-yield trade-off. These single-donor pilot findings offer preliminary, quantitative guidance for pre-sampling conditions in saliva-based genomic analyses, to be validated in multi-donor cohorts.</p>","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537997","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":"Exploratory strain-associated patterns of antiviral transcriptional responses to Zika virus exposure in developing human neural tissue.","authors":"Zahra Abedi, Mohammad Ali Sheikh Beig Goharrizi, Amirreza Abbasi, Negar Sadat Soleimani Zakeri, Helia Jangi, Alireza Susanabadi Farahani","doi":"10.1186/s44342-026-00076-5","DOIUrl":"10.1186/s44342-026-00076-5","url":null,"abstract":"<p><p>Zika virus (ZIKV) infection affects early human brain development, but it is still not fully clear how different developmental cell lineages shape antiviral transcriptional responses. In this study, we carried out a secondary descriptive analysis using publicly available single-cell transcriptomic datasets from human fetal brain-derived neural tissue exposed ex vivo to Brazilian ZIKV-BR, the Cambodian 2010 Asian-lineage FSS13025 isolate, referred to here as ZIKV-FSS, or interferon-beta stimulation (IFNβ). Across neural lineages, radial glia-like cells enriched in progenitors and cycling NPC populations showed strong transcriptional IFN/ISG responsiveness and a higher number of genes that met exploratory differential expression criteria compared with several other cell types. Exploratory comparisons suggested strain-associated differences in response structure. In selected progenitor-focused and ISG-related summaries, the patterns linked to ZIKV-FSS showed more descriptive similarity to IFNβ-related profiles, while ZIKV-BR exposure was linked to broader and more varied gene expression changes. Sensitivity analyses showed that the transcriptional similarity between ZIKV and IFNβ depended on the gene universe used, was strongest among canonical interferon-stimulated genes (ISGs), and was more conservative across broader non-ISG and all-expressed gene sets. Contextual analyses of an independent human cerebral organoid bulk RNA-seq dataset and a Vero/moDC single-cell dataset supported the general presence of IFN/ISG-related transcriptional activation across ZIKV-exposed systems, but these were not interpreted as validation of fetal neural lineage-specific responses. Overall, these results provide an exploratory, lineage-resolved descriptive reference of antiviral transcriptional states in developing human neural tissue. Since the main fetal neural dataset included only one biological sample per condition, these findings should be interpreted as exploratory strain-associated patterns rather than definitive evidence for strain-dependent mechanisms.</p>","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148427885","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":"Design of a multi-epitope vaccine against Mycobacterium tuberculosis using reverse vaccinology and immunoreactive peptides.","authors":"Narjes Noori Goodarzi, Sepideh Fereshteh, Behzad Shahbazi, Niloofar Rezaie, Mahshid Khazani Asforooshani, Farzad Badmasti","doi":"10.1186/s44342-026-00075-6","DOIUrl":"10.1186/s44342-026-00075-6","url":null,"abstract":"<p><strong>Background: </strong>Mycobacterium tuberculosis infects one-fourth of the global population, and current challenges such as latent infections, multidrug-resistant strains, and the limited efficacy of the BCG vaccine emphasize the urgent need for next-generation vaccines. This study aimed to introduce novel vaccine candidates, immunoreactive epitopes, and a novel multi-epitope vaccine (MEV).</p><p><strong>Methods: </strong>New immunogenic targets were identified based on different characteristics, including subcellular localization, antigenicity, non-similarity to the host proteome, sequence conservation, prevalence, and B-cell and T-cell epitopes. In the next step, IFN-γ releasing immunoreactive epitopes with a high similarity to TCR-interacting epitopes were identified. The MEV was generated using shortlisted epitopes and the C-terminal fragment of Clostridium perfringens enterotoxin (CPE). Finally, the interactions of MEV epitopes with human MHC I and MHC II alleles were investigated.</p><p><strong>Results: </strong>In the first step, a total of seven proteins with desired immunogenic properties were introduced as novel immunogenic targets. Comparison of surface-exposed proteins to 4718 immunoreactive linear B-cell epitopes of M. tuberculosis resulted in identification of 719 non-redundant immunoreactive epitopes. Finally, seven immunoreactive, IFN-γ releasing epitopes with significant homology to TCR binding epitopes were employed to design a MEV. This MEV showed desirable structural and immunogenic properties. Moreover, it revealed promising interactions with human MHC I and MHC II alleles in molecular docking.</p><p><strong>Conclusion: </strong>This study suggests PE/PPE proteins and TCR-recognized immunoreactive peptides as promising vaccine components against tuberculosis. In addition, the designed MEV with the C-terminal fragment of CPE may represent a potential candidate for future development as a mucosal vaccine against M. tuberculosis.</p>","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148414570","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}