Frontiers in Genetics最新文献

{"title":"Identification of the U-box gene family in peach (<i>Prunus persica</i>) and functional analysis of <i>PpPUB20</i> in response to salt stress.","authors":"Huiwen Zhang, Ruxuan Guo, Xiaoshuang Zhang, Chongyu Zhao, Junkai Wu, Xiao Xiao, Yanhong Shen, Chunsheng Liu, Gang Li, Kai Su, Kun Xiao, Chenguang Zhang, Libin Zhang","doi":"10.3389/fgene.2025.1549981","DOIUrl":"10.3389/fgene.2025.1549981","url":null,"abstract":"<p><strong>Background: </strong>With the rising proportion of saline soils in the global irrigated soil area, improving salt stress tolerance in peach is of great significance and value for the development of peach industry. Plant U-box proteins (PUBs) are widely involved in various stress response processes. In this study, genome-wide identification and analysis of PUBs genes in cultivated peach were carried out, and the expression profiles of peach PUB genes in different tissues of peach as well as their responses under salt stress were also investigated.</p><p><strong>Methods: </strong>The genome-wide identification of PUBs genes in cultivated peach was analysed by gene localisation, gene structure and evolutionary analysis. Subsequently, the expression profiles of PpPUB genes in different tissues of peach and the changes in the relative expression of peach PUB genes under ABA, GA3, IAA, 6-BA treatments, low-temperature stress and salt stress were investigated.</p><p><strong>Results and discussion: </strong>In this study, 51 U-box protein genes (PUB) were identified in the cultivated peach \"<i>SJZX</i>\" and divided into six groups. Most of the PpPUB were predicted to be located in the nucleus and chloroplasts. Promoter analyses indicated that most members may be associated with lightresponsive processes. Expression analysis based on RT-qPCR showed that most PUB members in peach were highly expressed in a certain tissues or organs. Based on the results of RT-qPCR expression analysis of 18 representative PpPUB after abiotic stress and hormone induction, all detected genes except for PpPUB19 were induced by salt stress, and <i>PpPUB3/20/23/49</i> were induced by low temperature. Multiple genes were induced or repressed by exogenous hormone treatments. Furthermore, Arabidopsis seedlings heterologously overexpressing <i>PpPUB20</i> exhibited greater salt tolerance than wild-type seedlings under the same salt stress conditions. These findings provide comprehensive information on the <i>PpPUB</i> family and identify <i>PpPUB</i> members that may be involved in the regulation of hormones and salt stress. Therefore, this study enhances the understanding of potential role of <i>PpPUB</i> in stress adaptation in peach, thereby establishing a foundation for subsequent functional investigations and applications in stress-resistant crop breeding.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1549981"},"PeriodicalIF":2.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and codon usage analyses reveal the evolution of the seoul virus.","authors":"Yamei Wei, Yanan Cai, Xu Han, Zhanying Han, Yanbo Zhang, Yonggang Xu, Caixiao Jiang, Qi Li","doi":"10.3389/fgene.2025.1544577","DOIUrl":"10.3389/fgene.2025.1544577","url":null,"abstract":"<p><strong>Introduction: </strong>Seoul virus (<i>Orthohantavirus seoulense</i>, SEOV), a member of the <i>Hantaviridae</i>, causes hemorrhagic fever with renal syndrome (HFRS) through rodent hosts. However, its molecular evolutionary dynamics and codon usage patterns remain poorly understood.</p><p><strong>Methods: </strong>This study integrated coding sequences from GenBank and previously acquired SEOV strains to systematically analyze genetic evolution and codon usage bias.</p><p><strong>Results: </strong>It revealed that SEOV evolved seven clades (A-G) with distinct amino acid variation sites and geographic clustering. Recombination events were identified during evolution, alongside purifying and positive selection on specific sites (e.g., codon 259 in the S segment and codon 11 in the M segment). The three viral segments (L, M, and S) exhibited weak codon usage bias, predominantly driven by natural selection, with host adaptation significantly influencing evolutionary trajectories. The S segment demonstrated the strongest pathogenicity due to its closer codon usage alignment with <i>Homo sapiens</i> (<i>H. sapiens)</i> and <i>Rattus norvegicus</i> (<i>R. norvegicus</i>), whereas the L segment showed the lowest host adaptation. Divergent codon preferences among clades highlighted adaptive strategies in host-virus interactions.</p><p><strong>Conclusion: </strong>These findings elucidate the evolutionary mechanisms of SEOV and provide a theoretical foundation for live attenuated vaccine design and region-specific viral control strategies.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1544577"},"PeriodicalIF":2.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic reprogramming and prognostic modeling in pancreatic cancer: insights from WGCNA.","authors":"Zhuo Song, Zhijia Sun, Yupeng Di, Xu Liu, Xiaoli Kang, Gang Ren, Yingjie Wang","doi":"10.3389/fgene.2025.1487046","DOIUrl":"10.3389/fgene.2025.1487046","url":null,"abstract":"<p><strong>Purpose: </strong>Metabolic reprogramming plays a crucial role in multiple malignant features of pancreatic cancer (PC). However, few studies have comprehensively examined metabolic features of PC and provided guidance for their treatment.</p><p><strong>Methods: </strong>This study tried to identify metabolism-associated hub genes based on metabolic phenotypic levels through weighted gene co-expression network analysis, and constructed a risk model for PC, then verified its accuracy and explored the potential mechanisms.</p><p><strong>Results: </strong>We screened out five metabolic hub and prognostic genes (<i>DLX3, HMGA2, SPRR1B, MYEOV</i>, and <i>FAM111B</i>) and constructed a novel metabolism-associated gene signature to predict the prognosis of PC. The model was verified efficacy and demonstrated with good performance through analysis of Kaplan-Meier plotter, receiver operating characteristic curves, comparing with reported models, application in predicting drug sensitivity and constructing a nomogram model. Correlation analysis revealed a close association between the levels of risk score and DNA damage response (DDR, correlation coefficient: 0.41, <i>P</i> < 0.001). Enrichment analysis indicated that risk scores were derived from multiple metabolic or proliferative pathways, providing further evidence that metabolism may mediate DDR to affect PC survival.</p><p><strong>Conclusion: </strong>Through bioinformatics analysis, we identified five prognostic relevant differentially expressed genes highlighting the role of metabolism-associated factors in pancreatic cancer, which reveals a strong correlation ship with DDR, offering new insights into treatment strategies that combine metabolism with DDR.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1487046"},"PeriodicalIF":2.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parentage assignment in black soldier fly (<i>Hermetia illucens</i>) using genotyping-by-sequencing.","authors":"Guyllaume Dufresne, Catherine Bolduc, Christopher Warburton, Grant Vandenberg, Marie-Hélène Deschamps, Nabeel Alnahhas","doi":"10.3389/fgene.2025.1541812","DOIUrl":"10.3389/fgene.2025.1541812","url":null,"abstract":"<p><p>Genetic selection to optimize economically important traits in black soldier flies (BSF), a major species in the insects as food and feed industry, continues to gain interest. Tracking pedigrees is a prerequisite for generating genetic progress while conserving the genetic variability of traits under selection. However, this is not currently feasible in mass reared insects like BSF. As an alternative, this study identified SNPs informative for parentage assignment (PA) in a commercial and laboratory colony of BSF using genotyping-by-sequencing (GBS). We first established an experimental population of 12 BSF families per colony by randomly mating flies within each family over three generations. DNA was then sequenced from mated pairs and two larvae per pair per generation (n = 288 samples). After SNP calling and filtering, we generated four high-quality SNP subsets containing 192, 118, 72, and 51 SNPs, respectively. PA was conducted using a likelihood-based method across simulated inbreeding rates from 0% to 100%. Compared to known parents, PA accuracy reached 100% across all SNP subsets and inbreeding rates. However, assignment confidence as measured by the log-likelihood (LOD) score decreased significantly as the number of SNPs decreased, though inbreeding had no significant effect on LOD scores. High-confidence assignments to either male or female parents required all 192 SNPs, whereas high-confidence assignments to parent pairs were possible with 118 or 192 SNPs. The identified SNPs provide a valuable resource for developing low-density panels to implement pedigree-based selection and to manage genetic diversity, thereby supporting the development of breeding programs in BSF.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1541812"},"PeriodicalIF":2.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a novel <i>AGO2</i> variant causing LESKRES in a Chinese family with intellectual disability.","authors":"Shufa Yang, Wei Song, Yousheng Yan","doi":"10.3389/fgene.2025.1598462","DOIUrl":"10.3389/fgene.2025.1598462","url":null,"abstract":"<p><strong>Background: </strong>Lessel-Kreienkamp syndrome (LESKRES, MIM #619149), an autosomal dominant genetic disorder caused by variants in <i>AGO2</i> (MIM*606229), primarily leads to neurodevelopmental symptoms.</p><p><strong>Objective: </strong>This study aims to investigate the genetic etiology of a family with intellectual disability.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was used to initially identify the pathogenic variants responsible for the intellectual disability in the family, and Sanger sequencing was employed for confirmation. Complete family information was collected, and Sanger sequencing was performed to confirm the co-segregation of the variant with the intellectual disability, thereby determining the pathogenicity of the novel variant. The pathogenicity of the novel variant was evaluated using <i>in silico</i> methods.</p><p><strong>Results: </strong>All four intellectual disability individuals carried the novel <i>AGO2</i> (NM_012154.5): c.2149T>C (p.Cys717Arg) variant, while the other individuals did not. According to ACMG guidelines, this novel variant is classified as likely pathogenic. The novel variant occurs at a conserved position in <i>AGO2</i> and is predicted to affect the 3D structure of the <i>AGO2</i> protein.</p><p><strong>Conclusion: </strong>This study identifies a novel <i>AGO2</i> variant causing LESKRES in the Chinese population for the first time. Our findings expand the variants spectrum of <i>AGO2</i> leading to LESKRES and highlight the value of WES in diagnosing genetic causes of intellectual disabilities.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1598462"},"PeriodicalIF":2.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly multiplexed molecular inversion probe panel in <i>Plasmodium falciparum</i> targeting common SNPs approximates whole-genome sequencing assessments for selection and relatedness.","authors":"Karamoko Niaré, Rebecca Crudale, Abebe A Fola, Neeva Wernsman Young, Victor Asua, Melissa D Conrad, Pierre Gashema, Anita Ghansah, Stan Hangi, Deus S Ishengoma, Jean-Baptiste Mazarati, Ayalew Jejaw Zeleke, Philip J Rosenthal, Abdoulaye A Djimdé, Jonathan J Juliano, Jeffrey A Bailey","doi":"10.3389/fgene.2025.1526049","DOIUrl":"10.3389/fgene.2025.1526049","url":null,"abstract":"<p><strong>Introduction: </strong>The use of next-generation sequencing technologies (NGS) to study parasite populations and their response and evolution to interventions is important to support malaria control and elimination efforts. While whole-genome sequencing (WGS) is optimal in terms of assessing the entire genome, it is costly for numerous samples. Targeted approaches selectively enriching for the sequence of interest are more affordable and have higher throughput but sometimes lack adequate information content for key analyses.</p><p><strong>Methods: </strong>We have developed a highly multiplexed molecular inversion probe (MIP) panel (IBC2FULL) targeting 4,264 single-nucleotide polymorphisms (SNPs) with ≥5% minor allele frequency (MAF) in Sub-Saharan African regions from publicly available <i>Plasmodium falciparum</i> WGS (n = 3,693). We optimized the panel alone and in combination with antimalarial drug resistance MIPs in laboratory <i>P. falciparum</i> strains at different parasitemias and validated it by sequencing field isolates from the Democratic Republic of Congo, Ethiopia, Ghana, Mali, Rwanda, Tanzania, and Uganda and evaluating the population structure, identity-by-descent (IBD), signals of selection, and complexity of infection (COI).</p><p><strong>Results: </strong>The new panel IBC2FULL consisted of 2,128 MIPs (containing 4,264 common SNPs) spaced by 5.1-18.4 kb across the entire genome. While these microhaplotypes were developed based on variations from Sub-Saharan African WGS data, 59.3% (2,529) of SNPs were also common in Southeast Asia. The MIPs were balanced to produce more a uniform and higher depth of coverage at low parasitemia (100 parasites/μL) along with MIPs targeting antimalarial drug resistance genes. Comparing targeted regions extracted from public WGS, we observed that IBC2FULL provided a higher resolution of the local population structure in Sub-Saharan Africa than current PCR-based targeted sequencing panels. For sequencing field samples (n = 140), IBC2FULL approximated WGS measures of relatedness, population structure, and COI. Interestingly, genome-wide analysis of extended haplotype homozygosity detected the same major peaks of selection as WGS. We also chose a subset of 305 high-performing MIPs to create a core panel (IBC2CORE) that produced high-quality data for basic population genomic analysis and accurate estimation of COI.</p><p><strong>Discussion: </strong>IBC2FULL and IBC2CORE panels have been designed to provide an improved platform for malaria genomic epidemiology and biology that can approximate WGS for many applications and is deployable for malaria molecular surveillance in resource-limited settings.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1526049"},"PeriodicalIF":2.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 splicing characterization of COL4A5 mutations and prognostic significance in a single cohort with X-linked alport syndrome.","authors":"Haomiao Li, Shengnan Zhang, Wei Zhou, Chunli Wang, Chunhua Zhu, Sanlong Zhao, Fei Zhao, Zhanjun Jia, Aihua Zhang, Bixia Zheng, Guixia Ding","doi":"10.3389/fgene.2025.1564343","DOIUrl":"10.3389/fgene.2025.1564343","url":null,"abstract":"<p><strong>Introduction: </strong>X-linked Alport syndrome (XLAS), caused by mutations in the COL4A5 gene, is an X-linked hereditary disease typically characterized by renal failure, hearing loss, and ocular abnormalities. It is a leading hereditary cause of end-stage renal disease (ESRD) worldwide. Studies on the genotype-phenotype correlation in Alport syndrome suggest that splicing mutations result in more severe clinical phenotypes than missense mutations. Determining whether COL4A5 mutations lead to aberrant mRNA splicing is critical for diagnosis and prognosis.</p><p><strong>Methods: </strong>This study retrospectively reviewed pediatric XLAS patients with COL4A5 gene mutations from a single-center cohort, summarizing and analyzing their clinical features. Minigene assay was employed to evaluate the mRNA splicing functionality of 26 single-nucleotide variants (SNVs), both intronic and exonic, identified in XLAS patients. Bioinformatics tools were used to evaluate the accuracy and sensitivity of splicing mutation prediction. Additionally, linear mixed models were applied to analyze the relationship between mutation types and prognosis in patients' estimated glomerular filtration rate (eGFR), exploring genotype-phenotype correlations.</p><p><strong>Results: </strong>In this cohort, we screened 41 XLAS pediatric patients, including 32 with confirmed XLAS and nine suspected XLAS. The cohort included 21 males (51.2%) and 20 females (48.8%), with a median age at onset of 4.42 years. Among the patients, 22 presented with both hematuria and proteinuria, while 18 exhibited hematuria alone. Notably, only one patient had isolated proteinuria. Regarding mRNA splicing, among the 26 intronic and exonic SNVs, 10 mutations (38.5%) were found to cause aberrant mRNA splicing, as demonstrated by the minigene assay. Sensitivity and specificity assessments of bioinformatics tools revealed that ESE Finder demonstrated higher sensitivity, while RNA Splicer exhibited greater specificity. Furthermore, These splicing abnormalities were closely associated with a faster decline in eGFR.</p><p><strong>Conclusion: </strong>This study demonstrates that 38.5% of SNVs in the COL4A5 gene result in aberrant mRNA splicing, which is closely linked to renal function decline in XLAS. Splicing mutations are correlated with more rapid renal progression, highlighting the importance of determining the splicing effects of SNVs during genetic screening for XLAS.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1564343"},"PeriodicalIF":2.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning driven multi-omics analysis of the genetic mechanisms behind the double-coat fleece formation in Hetian sheep.","authors":"Yanwei Zhang, Wenrong Li, Xinming Xu, Mengwan Xie, Liping Tang, Peiyu Zheng, Nannan Song, Lijuan Yu, Jiang Di","doi":"10.3389/fgene.2025.1582244","DOIUrl":"10.3389/fgene.2025.1582244","url":null,"abstract":"<p><strong>Introduction: </strong>The double-coated fleece is crucial for the adaptability and economic value of Hetian sheep, yet its underlying molecular mechanisms remain largely unexplored.</p><p><strong>Methods: </strong>We integrated genome and transcriptome data from double-coated Hetian sheep and single-coated Chinese Merino sheep. Candidate genes associated with coat fleece type and environmental adaptation were identified using combined selective sweep and differential expression analyses. Subsequent analyses included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction (PPI) network construction, and machine learning-based screening.</p><p><strong>Results: </strong>Selective sweep and differential expression analyses identified 101 and 106 candidate genes in Hetian sheep and Chinese Merino sheep, respectively. Enrichment analyses revealed these genes were primarily involved in pathways related to wool growth and energy metabolism. PPI network analysis and machine learning identified IRF2BP2 and EGFR as key functional genes associated with coat fleece type.</p><p><strong>Discussion: </strong>This study enhances understanding of the genetic mechanisms governing double-coated fleece formation in Hetian sheep. The identification of key genes (IRF2BP2, EGFR) and the methodological approach provide valuable insights for developing machine learning-driven multi-omics selection models in sheep breeding.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1582244"},"PeriodicalIF":2.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iKcr-DRC: prediction of lysine crotonylation sites in proteins based on a novel attention module and DenseNet.","authors":"Xin Wei, Siqin Hu, Jian Tu, Muhammad Akmal Remli","doi":"10.3389/fgene.2025.1574832","DOIUrl":"10.3389/fgene.2025.1574832","url":null,"abstract":"<p><strong>Introduction: </strong>Lysine crotonylation (Kcr) is a recently identified post-translational modification that predominantly occurs on lysine residues and plays a crucial role in regulating gene expression, cellular metabolism, and various biological processes. Increasing evidence has linked Kcr to the pathogenesis of major diseases such as cancer, highlighting the importance of accurately identifying Kcr sites for understanding disease mechanisms and normal cellular function.</p><p><strong>Methods: </strong>In this study, we present a novel deep learning-based computational model, named iKcr-DRC, for the accurate prediction of lysine crotonylation sites. The model leverages a densely connected convolutional network (DenseNet) as its backbone to effectively capture high-level local features from protein sequences. Additionally, we introduce an enhanced channel attention mechanism with a short-circuit connection design, endowing the network with residual properties and improved feature refinement capabilities.</p><p><strong>Results: </strong>The experimental results show that the iKcr-DRC model achieves 90.30%, 78.35%, 84.33% and 69.15% for sensitivity, specificity, accuracy, and Matthew's correlation coefficients, respectively. These results indicate a significant improvement over existing state-of-the-art Kcr prediction tools.</p><p><strong>Discussion: </strong>The proposed iKcr-DRC model provides an effective and innovative approach for predicting lysine crotonylation sites. It holds great potential for advancing applications in bioinformatics and enhancing the understanding of protein post-translational modifications. An online prediction tool based on the iKcr-DRC model is freely accessible at: http://www.lzzzlab.top/ikcr/.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1574832"},"PeriodicalIF":2.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exome sequencing and prenatal skeletal abnormalities: comprehensive review and meta-analysis and way forward.","authors":"Mengting Jiang, Bin Zhang, Jing Wang, Cui Wei, Xiuzhen Mao, Bin Yu","doi":"10.3389/fgene.2025.1502538","DOIUrl":"10.3389/fgene.2025.1502538","url":null,"abstract":"<p><strong>Objective: </strong>To assess the detection rate of exome sequencing (ES) in fetuses diagnosed as skeletal abnormalities (SKA) with normal karyotype or chromosomal microarray analysis (CMA) results.</p><p><strong>Methods: </strong>We conducted electronic searches in four databases, focusing on studies involving ES in fetuses with SKA. Additional detection rate of ES compared to karyotype/CMA was calculated, followed by a meta-analysis. Subgroup analyses explored the influence of fetal phenotype on diagnostic outcomes.</p><p><strong>Results: </strong>From 2,393 studies, 21 reports covering 476 fetuses were analyzed. Key findings include: (1) an additional detection rate of ES of 63.2% (Risk Difference (RD), 0.68 [95% CI, 0.60-0.76], p < 0.00001); (2) identification of 76 genes across 304 types of variants, with <i>FGFR3</i>, <i>COL1A1</i>, <i>COL1A2</i>, and <i>COL2A1</i> being prevalent; (3) lower detection rates in fetuses with isolated short long bones compared to non-isolated conditions, though not significantly different (p = 0.35); (4) higher detection rates in subgroups with abnormal ossification, small chest, suspected long bone fractures or angulations, and skull abnormalities.</p><p><strong>Conclusion: </strong>The meta-analysis indicates that genetic variation significantly contributes to fetal SKA, primarily due to single-gene variants. Consequently, ES should be used in the prenatal diagnosis of SKA fetuses in clinical practice.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1502538"},"PeriodicalIF":2.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}