Comparative and Functional Genomics最新文献

{"title":"Comprehensive and Combined Omics Analysis Reveals Immune–Infiltration-Associated Alternative Splicing and RBP Regulators Contributing to Ischemia–Reperfusion Injury in Liver Transplantation","authors":"Bincheng Gui, Hanfei Huang","doi":"10.1155/ijog/4835678","DOIUrl":"10.1155/ijog/4835678","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatic ischemia–reperfusion injury (HIRI) is a major cause of early allograft dysfunction after liver transplantation, but its post-transcriptional regulation remains poorly understood. This study aimed to characterize alternative splicing (AS) events in HIRI and explore a potential association network involving RNA-binding proteins (RBPs), AS, and immune responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the GSE151648 dataset (80 paired samples from 40 patients), we identified regulated alternative splicing (RAS) events and analyzed dynamic changes in immune cell populations. An RBP-RAS co-expression network was constructed, and single-cell data (GSE171539, one donor, three time points) were used to explore cell-type-specific expression of key RBPs in a qualitative, hypothesis-generating capacity. RBP expression changes were validated in an independent microarray cohort (GSE12720, 20 paired biopsies) and cross-validated with Human Protein Atlas liver proteomic data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mild IRI (IRI−) samples mainly exhibited alternative 5 <sup>′</sup>/3 <sup>′</sup> splice site events, whereas severe IRI (IRI+) samples were characterized by intron retention and overlapping exons, suggesting that severe injury may involve spliceosomal dysfunction. Post-transplantation, activated mast cells and NK cells increased, with a shift toward M0 macrophages and a decrease in M2 macrophages. Thirty immune-related RAS events significantly correlated with immune cell proportions (|<i>r</i>| ≥ 0.5, <i>p</i> < 0.01). An RBP-RAS network comprising 43 differentially expressed RBPs was constructed, showing coordinated co-variation between splicing factors and immune-associated splicing events. Single-cell analysis further revealed cell-type-specific expression patterns of multiple RBPs across hepatocytes, endothelial cells, and immune populations. External validation in GSE12720 confirmed that 39 of 42 detected RBPs (93%) were consistently upregulated post-reperfusion, and the Human Protein Atlas confirmed protein-level expression for 25 of 43 RBPs (58%) in normal liver tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study suggests that mild and severe HIRI are associated with distinct splicing programs and that these changes are closely associated with immune microenvironment remodeling, supporting the hypothesis of an RBP-AS-immune regulatory network. These findings, in which the RBP expression changes were independently validated in an external cohort, provide a basis for generat","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016746","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":"Correction to “Impact of Genetic Polymorphisms on the Efficacy and Safety of Isoniazid in Saudi Tuberculosis Patients”","authors":"","doi":"10.1155/ijog/9865175","DOIUrl":"10.1155/ijog/9865175","url":null,"abstract":"<p>Mai A. Alim A. Sattar Ahmad, Huda Mohammed Alkreathy, Ahmed Ali, Sherif Ahmed, Hala Makki, “Impact of Genetic Polymorphisms on the Efficacy and Safety of Isoniazid in Saudi Tuberculosis Patients,” <i>International Journal of Genomics</i> 2025 (2025): 6664418, https://doi.org/10.1155/ijog/6664418.</p><p>In the above-mentioned article, affiliations number 2 and 8 were included by error. These should be removed, and as such, authors Ahmed Ali and Hala Makki should be affiliated with affiliation 1. Due to these changes, the affiliations of author Sherif Ahmed have subsequently been renumbered.</p><p>The incorrect affiliation list is as follows:</p><p>Mai A. Alim A. Sattar Ahmad,1 Huda Mohammed Alkreathy,1 Ahmed Ali,2 Sherif Ahmed,3,4,5,6,7 and Hala Makki8</p><p>1 Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia</p><p>2 Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.</p><p>3 King Abdulaziz University, Faculty of Science, Biological Sciences Department, Jeddah, Saudi Arabia</p><p>4 King Abdulaziz University, Centre of Excellence for Bionanoscience Research, Jeddah, Saudi Arabia</p><p>5 King Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Saudi Arabia</p><p>6 Al Borg Diagnostics, R&D Department, Jeddah, Saudi Arabia</p><p>7 Ain Sham University, Faculty of Agriculture, Department of Genetics, Cairo, Egypt</p><p>8 Genomics and Biotechnology Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia</p><p>The corrected affiliation list and author affiliations are shown below:</p><p>Mai A. Alim A. Sattar Ahmad1, Huda Mohammed Alkreathy1, Ahmed Ali1, Sherif Ahmed2,3,4,5,6, Hala Makki1</p><p>1 Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia</p><p>2 Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia</p><p>3 Centre of Excellence for Bionanoscience Research, King Abdulaziz University, Jeddah, Saudi Arabia</p><p>4 Princess Al-Jawhara Al-brahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia</p><p>5 R&D Department, Al Borg Diagnostics, Jeddah, Saudi Arabia</p><p>6 Department of Genetics, Faculty of Agriculture, Ain Shams University, Cairo, Egypt</p><p>Additionally, there was an error in the Funding section. The text “This research project was funded by the King Abdulaziz University (10.13039/501100004054) (G: 184-248-1441)” was incorrect. The corrected section is shown below:</p><p><b>Funding</b></p><p>This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under Grant Number G:184-248-1441. The authors, therefore, acknowledge with thanks the DSR for its technical and financial support.</p><p>These errors have been corrected in the online version o","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016378","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":"Downregulation of IFNG-AS1 and UCHL1-AS1 in Peripheral Blood Cells of Multiple Sclerosis Patients: IFNG-AS1 as a Candidate Diagnostic Biomarker","authors":"Ali Rajabi,&nbsp;Jeffrey D. Gross,&nbsp;Ali Samadi","doi":"10.1155/ijog/7231094","DOIUrl":"https://doi.org/10.1155/ijog/7231094","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease affecting gray and white matter in the brain. Due to the highly variable presentation of MS, making a reliable long-term diagnosis based solely on initial clinical findings is extremely challenging. Long noncoding RNAs (lncRNAs) have been shown in recent research to have a role as prospective biomarkers that may offer data to forecast the onset and course of disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 100 healthy controls and 120 MS patients with 98 relapsing-remitting (RR), 10 primary progressive (PP), and 12 secondary progressive (SP) cases were included in the blood sample collection. Gene expression was assessed with quantitative real-time PCR. The receiver operating characteristic (ROC) curve analysis was employed to evaluate the potential for diagnostic analysis of lncRNA levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expressions of IFNG-AS1 and UCHL1-AS1 were found to be significantly decreased (<i>p</i> &lt; 0.0001) in patients compared to the control group. After adjustment for age using ANCOVA, IFNG-AS1 expression remained significantly lower in MS patients than in healthy controls (<i>p</i> &lt; 0.0001). IFNG-AS1 may be considered a potential biomarker for MS diagnosis (AUC = 0.838).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IFNG-AS1 demonstrates promising diagnostic potential for MS, whereas UCHL1-AS1 shows only modest discriminatory value. However, these findings are preliminary and require further validation with functional studies to confirm clinical utility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/7231094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994355","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":"Mechanistic Perspectives From Genomics and Pangenomics of Medicinal and Aromatic Plants: Linking Genome Architecture to Phytochemical Diversity","authors":"Himanshu Saini,&nbsp;Jyoti Yadav,&nbsp;Vishal Johar,&nbsp;Shalu Vyas,&nbsp;Vikrant Jaryan,&nbsp;Atin Kumar,&nbsp;Deepak Nanda,&nbsp;Anand Kumar,&nbsp;Jeevan Jyoti Kaushik,&nbsp;Sahil Shamkuwar,&nbsp;Shubham Singh","doi":"10.1155/ijog/2966459","DOIUrl":"10.1155/ijog/2966459","url":null,"abstract":"<p>Medicinal and aromatic plants (MAPs) produce a remarkable diversity of specialized metabolites with significant pharmaceutical, nutraceutical, and industrial value. Although advances in long-read sequencing, chromosome-scale genome assembly, and pangenomics have greatly expanded genomic resources, the mechanistic links between genome architecture and phytochemical diversity remain incompletely understood. The present review synthesizes current evidence describing how structural genomic variation may contribute to phytochemical diversity, while acknowledging that many proposed genome-to-metabolite relationships require further experimental validation. Examples illustrate how genome architecture is associated with specialized-metabolite biosynthesis through multiple regulatory processes. However, the strength of supporting evidence varies considerably among MAP species. Moreover, relatively few genome-to-metabolite relationships have been confirmed through direct functional validation. We further discuss how pangenomics, multiomics integration, genome editing, synthetic biology, and artificial intelligence support the discovery, validation, and engineering of specialized metabolic pathways. Casual conclusions are evaluated according to the strength of available evidence, highlighting where causal relationships have been experimentally established and where conclusions remain primarily association-based. Overall, this review provides an integrated conceptual and evidence-based perspective summarizing proposed relationships between genome architecture and phytochemical diversity and outlines future priorities for functional genomics, precision breeding, metabolic engineering, and sustainable utilization of MAPs.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976288","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 and Analysis of Biomarkers Associated With RNA Modification in Idiopathic Nephrotic Syndrome Using Single-Cell Transcriptome Data","authors":"Yuan Lin,&nbsp;Juan Tu,&nbsp;Huarong Li,&nbsp;Chaoying Chen","doi":"10.1155/ijog/5053849","DOIUrl":"https://doi.org/10.1155/ijog/5053849","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Idiopathic nephrotic syndrome (INS) is the most prevalent glomerular disease in children, and RNA modification might play a pivotal role in its pathogenesis. However, the mechanisms connecting RNA modification to INS remain poorly elucidated. This study investigated the intrinsic mechanisms of INS by comprehensively analyzing single-cell transcriptomic data in conjunction with RNA modification-related genes (RRGs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>INS-related single-cell transcriptome data were obtained from a public database, and RRGs were curated from the literature. Key cells and biomarkers were identified in both INS and healthy samples through single-cell RNA sequencing and protein–protein interaction analyses. We characterized the molecular profiles of the biomarkers, constructed regulatory networks, and identified potential drugs through drug prediction and molecular docking. Furthermore, dynamic biomarker expression and intercellular interactions were explored through cell communication and pseudotime analyses, providing a theoretical basis for the clinical treatment of INS in children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>B cells were identified as key cells in INS, and <i>RBM25</i> and <i>PRPF40A</i> were established as biomarkers. Notably, <i>RBM25</i> was primarily localized in the cytoplasm and encoded on chromosome 14, whereas <i>PRPF40A</i> was predominantly found in the nucleus and encoded on chromosome 2. The molecular regulatory network revealed that the highest activity scores in B cells were associated with <i>EBF1</i>(+), <i>TCF4</i>(+), <i>MEF2C</i>(+), <i>SOX5</i>(+), and <i>POU2F2</i>(+). Additionally, fulvestrant was identified as a drug targeting both biomarkers. Finally, the key receptor–ligand pair MIF–CD74/CXCR4 between NK and B cells was identified through cellular communication and pseudotime analyses, with biomarker expression decreasing during middifferentiation and increasing in later stages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Based on single-cell transcriptomics, this study has preliminarily identified B cells as key cells in INS and screened <i>RBM25</i> and <i>PRPF40A</i> as biomarkers, providing initial theoretical insights for the exploration of subsequent targeted therapies. However, due to limitations in sample size, these findings still need to be validated in a larger, independent cohort.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/5053849","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942733","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":"IL1RAP Is Associated With an Inflammation–Immunity–Related State in Skin Cutaneous Melanoma: Integrative Evidence From Pan-Cancer Data and Melanoma Immunotherapy Cohorts","authors":"Chenxi Jiang,&nbsp;Hairui Li,&nbsp;Jianqiong Huang,&nbsp;Maojun Chen","doi":"10.1155/ijog/3751729","DOIUrl":"10.1155/ijog/3751729","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The crosstalk between inflammation and immunity plays a central role in tumor progression, immune evasion, and therapeutic response. Interleukin-1 receptor accessory protein (IL1RAP) is a key adaptor in inflammatory signaling, yet its immunological relevance and clinical implications in skin cutaneous melanoma (SKCM) remain largely unexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed an integrative analysis combining pan-cancer and melanoma-focused datasets. Bulk transcriptomic, single-cell, spatial transcriptomic, genomic alteration, pharmacogenomic, and clinical survival data were obtained from TCGA, GTEx, GEO, ENA, and other public resources. IL1RAP expression was evaluated across cancer types in relation to diagnostic performance, immune subtypes, survival outcomes, functional pathway activity, immune–genomic states, somatic alterations, and drug-response metrics. Melanoma-focused analyses examined immune infiltration, methylation-derived tumor-infiltrating lymphocyte (MeTIL) scores, and exploratory survival associations in five treatment cohorts; the survival groups were defined using cohort-specific optimal cutoffs rather than median splits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IL1RAP expression differed between tumor and normal tissues in multiple cancers, although the direction and magnitude varied by cancer type. Pan-cancer survival associations were likewise context dependent. Single-cell and spatial transcriptomic resources indicated cell-type and spatial heterogeneity of IL1RAP expression within tumor microenvironments. Pathway, immune–genomic, and pharmacogenomic analyses identified exploratory associations with functional states, genomic features, and drug-response metrics. In SKCM, IL1RAP expression was associated with several immune-infiltration estimates and higher MeTIL scores. Across five melanoma immunotherapy cohorts, the direction and magnitude of the overall survival associations varied substantially.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This retrospective integrative analysis suggests that IL1RAP may mark an inflammation–immunity–related state in SKCM. The heterogeneous associations across cancers and melanoma treatment cohorts support further validation but do not establish IL1RAP as a causal regulator, a treatment-response predictor, or a therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873894","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":"Single-Cell and Bulk Transcriptomic Integration Reveals an Adverse SPP1 Inflammatory TAM State and INHBA as a Candidate Biomarker in Non-Small Cell Lung Cancer Immunotherapy","authors":"Sheng Zhang,&nbsp;Guojun Zhang,&nbsp;Wenxuan Wang,&nbsp;Hong Luo,&nbsp;Huaping Chen","doi":"10.1155/ijog/2321522","DOIUrl":"10.1155/ijog/2321522","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Biomarkers that capture the microenvironmental basis of response to neoadjuvant immunotherapy in non-small cell lung cancer (NSCLC) remain limited. We integrated single-cell and bulk transcriptomic data to identify response-associated immune programs with patient-level relevance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-cell RNA-seq and clinical annotations from GSE207422 were used to construct an NSCLC tumor microenvironment atlas and refine myeloid and T cell states. UCell scoring, sample-level summaries, pseudobulk differential analysis, Monocle2 trajectory inference, and targeted macrophage–T cell interaction analysis were applied. A posttreatment SPP1 inflammatory TAM-derived NR-TAM signature was projected to pretreatment bulk RNA-seq from the same cohort. INHBA was evaluated in pretreatment bulk data, TCGA-LUAD/TCGA-LUSC, and lung cancer cell line assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SPP1 inflammatory TAM was enriched in nonmajor pathologic response (NMPR) samples and co-occurred with exhausted CD8 T cell abundance, malignant cell hypoxia, and EMT programs. The NR-TAM signature was partially recapitulated in pretreatment bulk RNA-seq, with higher scores in NMPR but substantial group overlap. Exploratory ROC analysis showed modest discrimination for NR-TAM score (AUC = 0.60), INHBA (AUC = 0.64), and the combined model (AUC = 0.64; LOOCV AUC = 0.37). INHBA was higher in NMPR cases, correlated with residual tumor burden and selected TAM-related genes, showed less favorable survival trends particularly in LUSC, and its knockdown reduced proliferation and migration in lung cancer cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>An SPP1 inflammatory TAM program is associated with unfavorable pathologic response in NSCLC neoadjuvant immunotherapy. INHBA is a prioritized exploratory candidate within this program. Because the evidence is associative and predictive performance is modest, these markers require prospective validation before clinical use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828199","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":"Novel Mutations in MTMR2 Gene Causes Charcot–Marie–Tooth Disease Type 4B1","authors":"Jun Yin,&nbsp;Santasree Banerjee","doi":"10.1155/ijog/3368910","DOIUrl":"https://doi.org/10.1155/ijog/3368910","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Charcot–Marie–Tooth (CMT) disease is the most prevalent and largest group of peripheral neuropathies, primarily affecting the peripheral nervous system. One of the rarest types of CMT is known as Charcot–Marie–Tooth disease, demyelinating, Type 4B1 (CMT4B1), with an autosomal recessive mode of inheritance. CMT4B1 is an axonal demyelination impacting both motor and sensory nervous systems, resulting in a slow and continuous decline in strength and wasting of muscles in both proximal and distal areas. In addition, CMT4B1 arises from inherited mutations in the <i>MTMR2</i> gene. So far, only 22 <i>MTMR2</i> germline variants have been reported for causing CMT4B1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we investigated and examined two Han Chinese patients who were clinically diagnosed with CMT4B1. However, the proband′s parents and younger brother were asymptomatic and normal. We performed whole exome sequencing and Sanger sequencing to identify the disease-causing variant in these probands.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Whole-exome sequencing identified two novel homozygous nonsense variants (c.618G &gt; A, p.Trp206∗ and c.1616C &gt; A, p.Ser539∗) in the <i>MTMR2</i> gene in these two patients, respectively. Sanger sequencing confirmed that both parents of these two patients carried these two novel variants in a heterozygous state, respectively. These two novel homozygous variants are predicted to lead to the formation of truncated MTMR2 proteins, which may cause complete loss of MTMR2 protein due to nonsense-mediated mRNA decay (NMD). Hence, these two novel variants are classified as <i>loss-of-function</i> variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our current research broadened the mutation profile of the <i>MTMR2</i> gene linked to CMT4B1 and highlighted the significance of utilizing whole-exome sequencing to identify pathogenic variants in CMT4B1 patients. Our study also provides, for the first time, a compilation of previously reported pathogenic variants of the <i>MTMR2</i> gene associated with CMT4B1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/3368910","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148848736","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":"Integrative Genomic Stratification of DNA Damage Repair–Associated Molecular Subtypes and Prognostic Modeling in Bladder Cancer","authors":"Hai Zhong,&nbsp;Lihua Zhang,&nbsp;Xiaoyan Xu,&nbsp;Ming Zhang,&nbsp;Xiaodan Yang,&nbsp;Lingyu Hu","doi":"10.1155/ijog/5475028","DOIUrl":"https://doi.org/10.1155/ijog/5475028","url":null,"abstract":"<p>Bladder cancer is characterized by substantial molecular heterogeneity that complicates prognostic assessment and therapeutic decision-making. DNA damage repair (DDR) pathways play a central role in maintaining genomic stability, yet a comprehensive genomics-based stratification framework centered on DDR alterations remains insufficiently defined. In this study, we performed an integrative genomic analysis of 406 bladder cancer samples from The Cancer Genome Atlas. Weighted gene coexpression network analysis was applied to identify bladder cancer–relevant DDR modules from a curated DDR gene set. Protein–protein interaction analysis prioritized 44 core DDR genes for molecular classification. Unsupervised consensus clustering revealed two DDR-associated molecular subtypes with significantly distinct overall survival and transcriptional programs. One subtype exhibited enrichment of immune-related pathways and stromal signatures, whereas the other was characterized by enhanced cell-cycle progression and DNA replication activity. To enable individualized prognostic prediction, an eight-gene DDR-associated signature was constructed using the least absolute shrinkage and selection operator and multivariable Cox regression analyses. The model effectively stratified patients into high- and low-risk groups and demonstrated stable predictive performance, with 1-, 3-, and 5-year area under the curve values of 0.745, 0.736, and 0.754, respectively. The signature was further evaluated in an independent GEO cohort (GSE13507), in which DDR-based clustering and risk stratification showed consistent prognostic trends, supporting the generalizability of the framework. High-risk tumors displayed increased tumor mutational burden, distinct immune infiltration patterns, and differential predicted drug sensitivity profiles. Protein-level validation supported dysregulated expression of key genes in tumor tissues. Collectively, this integrative genomics study establishes a DDR-centered molecular classification and prognostic framework, providing insights into genomic instability–driven heterogeneity and potential strategies for precision stratification in bladder cancer.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/5475028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753583","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 Lactylation- and Anoikis-Related Prognostic Signature Marks ECM-Remodeling CAFs and Immunosuppression in Gastric Cancer","authors":"Yue Fan,&nbsp;Yue Yu,&nbsp;Xian Jiang","doi":"10.1155/ijog/9137939","DOIUrl":"https://doi.org/10.1155/ijog/9137939","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Both anoikis resistance and lactate-driven protein lactylation are critical mechanisms of tumor progression; however, their synergistic prognostic value and combined impact on the gastric cancer (GC) microenvironment remain poorly understood. This study is aims to develop and biologically interpret a prognostic model integrating these two biological processes to improve patient stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified lactylation- and anoikis-related differentially expressed genes (LARDEGs) utilizing transcriptomic data from TCGA-STAD and GTEx. A prognostic signature was constructed via bootstrap LASSO-Cox regression and validated across two independent external cohorts (GSE62254 and GSE84437). To dissect the tumor microenvironment, we employed consensus clustering and immune deconvolution. Additionally, single-cell RNA sequencing (scRNA-seq) and intercellular communication algorithms were utilized to trace cellular origins, with key findings verified by qRT-PCR in 20 paired clinical GC samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 66 LARDEGs were identified, yielding an independent, four-gene prognostic signature (comprising <i>GPC3</i>, IGF2BP1, <i>LUM</i>, and <i>SOX9</i>). Tumors classified within the high-risk cohort exhibited pronounced stromal infiltration and an immunosuppressive landscape. Importantly, scRNA-seq mapping revealed that this signature is predominantly localized to a specific subpopulation of extracellular matrix (ECM)-remodeling cancer-associated fibroblasts (CAFs). Intercellular network analysis indicated that these ECM-remodeling CAFs are predicted to interact with myeloid and T cells via the COLLAGEN-<i>CD44</i> and <i>MIF-CD74</i> pathways, consistent with an immunosuppressive role. Furthermore, qRT-PCR analysis confirmed the significant upregulation of <i>LUM</i>, <i>SOX9</i>, <i>GPC3</i>, and the CAF marker <i>POSTN</i> in clinical GC tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The proposed four-gene signature accurately stratifies GC prognosis and mechanistically links lactylation and anoikis programs to a specific ECM-remodeling CAF subset. These CAFs orchestrate an immunosuppressive niche, thereby providing biologically interpretable risk stratification and novel therapeutic insights for high-risk patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/9137939","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753005","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}