BMC Genomics最新文献

{"title":"BDH1 identified by transcriptome has a negative effect on lipid metabolism in mammary epithelial cells of dairy goats.","authors":"Mengke Ni, Saige Zang, Yihan Wang, Xiaochen Qin, Min Tian, Tiantian Xiong, Chong Chen, Yue Zhang, Jun Luo, Cong Li","doi":"10.1186/s12864-025-11245-1","DOIUrl":"10.1186/s12864-025-11245-1","url":null,"abstract":"<p><strong>Background: </strong>The 3-hydroxybutyrate dehydrogenase 1 (BDH1) mainly participates in the regulation of milk fat synthesis and ketone body synthesis in mammary epithelial cells. In our previous study, BDH1 was identified as a key candidate gene regulating lipid metabolism in mammary glands of dairy goats by RNA-seq. This study aimed to investigate the effect of BDH1 on lipid metabolism in mammary epithelial cells of dairy goats (GMECs).</p><p><strong>Results: </strong>The results suggest that BDH1 plays a significant role in reducing triacylglycerol content and lipid droplet accumulation in GMECs (p < 0.05). Overexpression of BDH1 significantly decreased the expression of lipid metabolism-related genes (SREBF1 and GPAM) and reduced the levels of C14:0 and C17:1, while increasing FABP3 expression and C10:0 concentration (p < 0.05). Interference with BDH1 significantly increased the expression of SREBF1 and GPAM and the concentration of C14:0, C15:1, and C20:1, but significantly decreased FABP3 and C18:0 (p < 0.05). Treatment of GMECs with β-hydroxybutyric acid (R-BHBA) significantly decreased the expression of FASN, ACACA, LPL, SREBF1, FABP3, ACSL1, GPAM, DGAT1, and triacylglycerol content, while significantly increasing the expression of BDH1 (p < 0.05). Interference with BDH1 rescued the reduction of cellular TAG content and the expression of FASN, LPL, SREBF1, ACSL1, and GPAM in BHBA-treated GMECs.</p><p><strong>Conclusion: </strong>In conclusion, BDH1 negatively regulates lipid metabolism in mammary glands of dairy goats. Furthermore, it may mitigate the inhibitory effect of R-BHBA on lipid metabolism in GMECs.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"66"},"PeriodicalIF":3.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights from the single-cell level: lineage trajectory and somatic-germline interactions during spermatogenesis in dwarf surfclam Mulinia lateralis.","authors":"Yajuan Li, Huilan Wei, Xiaoting Dai, Lijing Zhang, Liangjie Liu, Xiaomei Chen, Tian Liu, Ya Shu, Yaxin Yang, Shi Wang, Zhenmin Bao, Lingling Zhang","doi":"10.1186/s12864-025-11266-w","DOIUrl":"10.1186/s12864-025-11266-w","url":null,"abstract":"<p><strong>Background: </strong>Spermatogenesis is a complex process of cellular differentiation that commences with the division of spermatogonia stem cells, ultimately resulting in the production of functional spermatozoa. However, a substantial gap remains in our understanding of the molecular mechanisms and key driver genes that underpin this process, particularly in invertebrates. The dwarf surfclam (Mulinia lateralis) is considered an optimal bivalve model due to its relatively short generation time and ease of breeding in laboratory settings.</p><p><strong>Results: </strong>In this study, over 4,600 testicular cells from various samples were employed to identify single-cell heterogeneity on a more comprehensive scale. The four germ cell populations (spermatogonia, primary spermatocytes, secondary spermatocytes, and round spermatids/spermatozoa) and three somatic populations (follicle cell, hemocyte, and nerve cell) were characterized. The four types of germ cells exhibited disparate cell cycle statuses and an uninterrupted developmental trajectory, progressing from spermatogonia to spermatids/spermatozoa. Pseudotime analysis indicates that gene expression, translation, ATP metabolic process, and microtubule-based process are involved in the transition of germ cell types. Weighted gene coexpression network analysis (WGCNA) identified four modules corresponding to the four types of germ cells, as well as key transcription factors (e.g., MYC, SREBF1, SOXH) that may play a critical role in these cell types. Furthermore, our findings revealed that there is extensive bidirectional communication between the somatic cells and the germline cells, including the FGF and TGF-β signaling pathways, as well as other ligand-receptor pairs, such as NTN1-NEO1 and PLG-PLGRKT.</p><p><strong>Conclusions: </strong>This study provides a comprehensive single-cell transcriptome landscape of the gonad, which will contribute to the understanding of germ cell fate transition during spermatogenesis, and the development of germ cell manipulation technologies in mollusks.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"69"},"PeriodicalIF":3.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 resistance to pyrethroids with possible involvement of non-coding ribonucleic acids in Anopheles funestus, the major malaria vector in western Kenya.","authors":"Isaiah Debrah, Daibin Zhong, Maxwell G Machani, Godfrey Nattoh, Kevin O Ochwedo, Collins M Morang'a, Ming-Chieh Lee, Linda E Amoah, Andrew K Githeko, Yaw A Afrane, Guiyun Yan","doi":"10.1186/s12864-025-11260-2","DOIUrl":"10.1186/s12864-025-11260-2","url":null,"abstract":"<p><strong>Background: </strong>The resurgence of Anopheles funestus, a dominant vector of human malaria in western Kenya was partly attributed to insecticide resistance. However, evidence on the molecular basis of pyrethroid resistance in western Kenya is limited. Here, we reported metabolic resistance mechanisms and demonstrated that multiple non-coding Ribonucleic Acids (ncRNAs) could play a potential role in An. funestus resistance to pyrethroid in western Kenya. Anopheles funestus mosquitoes were sampled using aspiration methods in Bungoma, Teso, Siaya, Port Victoria and Kombewa in western Kenya. The F1 progenies were exposed to deltamethrin (0.05%), permethrin (0.75%), DDT (4%) and pirimiphos-methyl (0.25%) following WHO test guidelines. A synergist assay using piperonyl butoxide (PBO) (4%) was conducted to determine cytochrome P450s' role in pyrethroid resistance. RNA-seq was conducted on a combined pool of specimens that were resistant and unexposed, and the results were compared with those of the FANG susceptible reference strain. This approach aimed to uncover the molecular mechanisms underlying the observed phenotypic pyrethroid resistance.</p><p><strong>Results: </strong>Pyrethroid resistance was observed in all sites with an average mortality rate (MR) of 57.6%. Port Victoria had the highest level of pyrethroid resistance to permethrin (MR = 53%) and deltamethrin (MR = 11%. Teso had the lowest level of resistance to permethrin (MR = 70%) and deltamethrin (MR = 87%). Resistance to DDT was observed only in Kombewa (MR = 89%) and Port Victoria (MR = 85%). A full susceptibility to P-methyl (0.25%) was observed in all sites. PBO synergist assay revealed high susceptibility (> 98%) to pyrethroids in all the sites except for Port Victoria (MR = 96%). Whole transcriptomic analysis showed that most gene families associated with pyrethroid resistance comprised non-coding RNAs (67%), followed by immunity proteins (10%), cytochrome P450s (6%), cuticular proteins (5%), olfactory proteins (4%), glutathione S-transferases (3%), UDP-glycosyltransferases (2%), ATP-binding cassettes (2%) and carboxylesterases (1%).</p><p><strong>Conclusion: </strong>This study unveils the molecular basis of insecticide resistance in An. funestus in western Kenya, highlighting for the first time the potential role of non-coding RNAs alongside metabolic detoxification in pyrethroid resistance. Targeting non-coding RNAs for intervention development could help in insecticide resistance management.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"64"},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-ancestry genome-wide association analyses: a comparison of meta- and mega-analyses in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.","authors":"Alan Kuang, Marie-France Hivert, M Geoffrey Hayes, William L Lowe, Denise M Scholtens","doi":"10.1186/s12864-025-11229-1","DOIUrl":"10.1186/s12864-025-11229-1","url":null,"abstract":"<p><strong>Background: </strong>There is increasing need for effective incorporation of high-dimensional genetics data from individuals with varied ancestry in genome-wide association (GWAS) analyses. Classically, multi-ancestry GWAS analyses are performed using statistical meta-analysis to combine results conducted within homogeneous ancestry groups. The emergence of cosmopolitan reference panels makes collective preprocessing of GWAS data possible, but impact on downstream GWAS results in a mega-analysis framework merits investigation. We utilized GWAS data from the multi-national Hyperglycemia and Adverse Pregnancy Outcome Study to investigate differences in GWAS findings using a homogeneous ancestry meta-analysis versus a heterogeneous ancestry mega-analysis pipeline. Maternal fasting and 1-hr glucose and metabolomics measured during a 2-hr 75-gram oral glucose tolerance test during early third trimester pregnancy were evaluated as phenotypes.</p><p><strong>Results: </strong>For the homogeneous ancestry meta-analysis pipeline, variant data were prepared by identifying sets of individuals with similar ancestry and imputing to ancestry-specific reference panels. GWAS was conducted within each ancestry group and results were combined using random-effects meta-analysis. For the heterogeneous ancestry mega-analysis pipeline, data for all individuals were collectively imputed to the Trans-Omics for Precision Medicine (TOPMed) cosmopolitan reference panel, and GWAS was conducted using a unified mega-analysis. The meta-analysis pipeline identified genome-wide significant associations for 15 variants in a region close to GCK on chromosome 7 with maternal fasting glucose and no significant findings for 1-hr glucose. Associations in this same region were identified using the mega-analysis pipeline, along with a well-documented association at MTNR1B on chromosome 11 with both fasting and 1-hr maternal glucose. For metabolomics analyses, the number of significant findings in the heterogeneous ancestry mega-analysis far exceeded those from the homogeneous ancestry meta-analysis and confirmed many previously documented associations, but genomic inflation factors were much more variable.</p><p><strong>Conclusions: </strong>For multi-ancestry GWAS, heterogeneous ancestry mega-analysis generates a rich set of variants for analysis using a cosmopolitan reference panel and results in vastly more significant, biologically credible and previously documented associations than a homogeneous ancestry meta-analysis approach. Genomic inflation factors do indicate that findings from the mega-analysis pipeline may merit cautious interpretation and further follow-up.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"65"},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The accumulation of harmful genes within the ROH hotspot regions of the Tibetan sheep genome does not lead to genetic load.","authors":"Lixia Sun, Chao Yuan, Tingting Guo, Yaqin Bai, Zengkui Lu, Jianbin Liu","doi":"10.1186/s12864-025-11207-7","DOIUrl":"10.1186/s12864-025-11207-7","url":null,"abstract":"<p><strong>Background: </strong>Prolonged natural selection and artificial breeding have contributed to increased uniformity within the Tibetan sheep population, resulting in a reduction in genetic diversity and the establishment of selective signatures in the genome. This process has led to a loss of heterozygosity in specific genomic regions and the formation of Runs of Homozygosity (ROH). Current research on ROH predominantly focuses on inbreeding and the signals of selection; however, there is a paucity of investigation into the genetic load and selective pressures associated with ROH, both within these regions and beyond. On one hand, genes located situated ROH hotspot regions exhibit a degree of conservation in their genomic segments; on the other hand, these regions may also serve as critical loci for identifying signals of selection.</p><p><strong>Results: </strong>High-throughput re-sequencing technology was utilized to investigate the ROH hotspot regions across 11 Tibetan sheep populations, resulting in the identification of ten conserved genes (ARHGEF16, Tom1l2, PRDM16, PEMT, SREBF1, Rasd1, Nt5m, MED9, FLCN, RAI1) that are associated with lipid metabolism, lactation, and development. These genes exhibited highly conserved within the ROH hotspot regions across all Tibetan sheep populations. Employing the integrated haplotype score (iHS) method, we screened for selective sites within frequently observed ROH hotspot regions to elucidate genomic differences among Tibetan sheep populations. A comprehensive analysis was conducted, involving Rnhom, dN/dS ratios, missense/synonymous ratios, and loss-of-function (LOF)/synonymous ratios, to investigate the accumulation of deleterious genes and the associated genetic load both within and outside ROH hotspot regions. The results revealed a higher accumulation of deleterious genes and a reduced genetic load within the ROH regions.</p><p><strong>Conclusions: </strong>This study provides a comprehensive and precise genomic analysis and interpretation of Tibetan sheep, offering theoretical basis for genetic breeding and evolution in Tibetan sheep.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"60"},"PeriodicalIF":3.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide microsatellite characterization and their marker development and transferability in Broussonetia Species.","authors":"Xiaowen Jia, Hanyu Li, Ying Han, Lu Wang, Chanjuan Lai, Xi Liu, Pan Li, Zupei Lei, Yonghua Zhang","doi":"10.1186/s12864-025-11238-0","DOIUrl":"10.1186/s12864-025-11238-0","url":null,"abstract":"<p><strong>Background: </strong>Broussonetia papyrifera, B. monoica, and B. kaempferi belong to the genus Broussonetia (Moraceae). These three species hold significant economic and research values. However, few molecular markers have been effectively utilized for resource development and molecular genetic breeding of these species. Sequencing of their genomes allowed us to develop genomic markers (e.g. simple sequence repeats (SSRs)) and construct a high-density physical map.</p><p><strong>Results: </strong>A total of 369,557, 332,627, and 276,245 SSRs were identified in 13 high-quality assembled pseudochromosomes and their unassembled scaffolds for B. papyrifera, B. monoica, and B. kaempferi, respectively. Among the identified genomic SSRs across the three species, short repeat sequences were more abundant, while long repeat sequences constituted a smaller proportion. Additionally, the predominant repeat motifs in the SSRs of the three Broussonetia species were composed of 'A' and 'T' repeats. Using B. papyrifera genome as a reference, 4,419 common SSRs were identified among these three species, while 2,048 SSRs were specific to B. kaempferi, and 4,285 SSRs were specific to B. monoica. Distribution analysis indicated a notable similarity in the distribution patterns of SSRs across the pseudochromosomes of these three species. Furthermore, of the identified SSRs, 28%, 31%, and 24% were mapped to genes in B. papyrifera, B. kaempferi, and B. monoica, respectively. Genic-mapped SSRs may regulate biological processes by influencing gene activity and protein function. To verify SSRs polymorphism, we selected 30 ones from 10,752 potentially polymorphic SSRs loci for PCR amplification among these three species, all of which were successfully amplified and exhibited polymorphism across these three species.</p><p><strong>Conclusions: </strong>These findings are helpful for further research on the origin, evolution, and migration of Broussonetia species and also laid the foundation for the precise identification, systematic evaluation, and efficient utilization of the germplasm resources of Broussonetia species.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"61"},"PeriodicalIF":3.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics and metabolomics analyses of mechanism underlying bovine sperm cryoinjury.","authors":"Renzheng Zhang, Xiuyuan Wang, Ruili Liu, Yanfang Mei, Xiuping Miao, Jiaxu Ma, Lei Zou, Qiuyue Zhao, Xuejin Bai, Yajuan Dong","doi":"10.1186/s12864-025-11258-w","DOIUrl":"10.1186/s12864-025-11258-w","url":null,"abstract":"<p><strong>Background: </strong>The cryoinjury of semen during cryopreservation reduces sperm motility, constraining the application of artificial insemination (AI) in bovine reproduction. Some fertility markers, related to sperm motility before and after freezing have been identified. However, little is known about the biological mechanism through which freezing reduces sperm motility. This study investigated the selective effects of cryoinjury on high-motility sperm (HMS) and low-motility sperm (LMS) in frozen-thawed from the perspectives of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP levels. The molecular mechanism of decreased sperm motility caused by cryoinjury was explored through a joint analysis of 4D-label free quantitative proteomics and non-targeted metabolomics.</p><p><strong>Results: </strong>The results indicate that low levels of ROS and high degrees of MMP and ATP play a critical role in the survival of HMS during the freezing process. The sperm samples from the frozen-thawed HMS and LMS were analysed for proteomics and metabolomics, 2,465 proteins and 4,135 metabolites were detected in bovine sperm samples. In contrast to LMS, HMS have 106 proteins and 106 metabolites with high abundance expression, and 79 proteins and 223 metabolites with low abundance expression. Proteomics and metabolomics data exhibit that highly expressed antioxidant enzymes and metabolites in HMS can maintain sperm motility by regulating the ROS produced during freezing to prevent sperm from oxidative stress and apoptosis. Furthermore, the KEGG analysis of differential proteins and metabolites during the freezing process implies that the significant enrichment of glycolysis and cAMP in HMS can guarantee energy supply.</p><p><strong>Conclusions: </strong>The results provided that during the process of bovine sperm freezing, highly expressed antioxidant enzymes can regulate the reactive oxygen species levels to avoid oxidative stress and the glycolysis signalling pathway ensures ATP production can sustain frozen-thawed sperm motility.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"63"},"PeriodicalIF":3.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenome-wide association study of objectively measured physical activity in peripheral blood leukocytes.","authors":"Nicolas Fragoso-Bargas, Nancy S Mcbride, Sindre Lee-Ødegård, Deborah A Lawlor, Paul D Yousefi, Gunn-Helen Moen, Julia O Opsahl, Anne Karen Jenum, Paul W Franks, Rashmi B Prasad, Elisabeth Qvigstad, Kåre I Birkeland, Kåre R Richardsen, Christine Sommer","doi":"10.1186/s12864-025-11262-0","DOIUrl":"10.1186/s12864-025-11262-0","url":null,"abstract":"<p><strong>Background: </strong>Few studies have explored the association between DNA methylation and physical activity. The aim of this study was to evaluate the association of objectively measured hours of sedentary behavior (SB) and moderate physical activity (MPA) with DNA methylation. We further aimed to explore the association between SB or MPA related CpG sites and cardiometabolic traits, gene expression, and genetic variation.</p><p><strong>Results: </strong>For discovery, we performed cross sectional analyses in pregnant women from the Epigenetics in pregnancy (EPIPREG) sample with both DNA methylation (Illumina MethylationEPIC BeadChip) and objectively measured physical activity data (SenseWear™ Pro 3 armband) (European = 244, South Asian = 109). For EWAS of SB and MPA, two main models were designed: model (1) a linear mixed model adjusted for age, smoking, blood cell composition, including ancestry as random intercept, and model (2) which was additionally adjusted for the total number of steps per day. In model 1, we did not identify any CpG sites associated with neither SB nor MPA. In model 2, SB was positively associated (false discovery rate, FDR < 0.05) with two CpG sites within the VSX1 gene. Both CpG sites were positively associated with BMI and were associated with several genetic variants in cis. MPA was associated with 122 significant CpG sites at FDR < 0.05 (model 2). We further analyzed the ten most statistically significant MPA related CpG sites and found that they presented opposite associations with sedentary behavior and BMI. We were not able to replicate the SB and MPA-related CpG sites in the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC had available objectively measured physical activity data from Actigraph (without steps/day available) and leucocyte DNA methylation data collected during adolescence (n = 408, European).</p><p><strong>Conclusion: </strong>This study suggests associations of objectively measured SB and MPA with maternal DNA methylation in peripheral blood leukocytes, that needs to be confirmed in larger samples of similar study design.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"62"},"PeriodicalIF":3.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational analysis of congenital heart disease associated SNPs: unveiling their impact on the gene regulatory system.","authors":"Shikha Vashisht, Costantino Parisi, Cecilia L Winata","doi":"10.1186/s12864-025-11232-6","DOIUrl":"10.1186/s12864-025-11232-6","url":null,"abstract":"<p><p>Congenital heart disease (CHD) is a prevalent condition characterized by defective heart development, causing premature death and stillbirths among infants. Genome-wide association studies (GWASs) have provided insights into the role of genetic variants in CHD pathogenesis through the identification of a comprehensive set of single-nucleotide polymorphisms (SNPs). Notably, 90-95% of these variants reside in the noncoding genome, complicating the understanding of their underlying mechanisms. Here, we developed a systematic computational pipeline for the identification and analysis of CHD-associated SNPs spanning both coding and noncoding regions of the genome. Initially, we curated a thorough dataset of SNPs from GWAS-catalog and ClinVar database and filtered them based on CHD-related traits. Subsequently, these CHD-SNPs were annotated and categorized into noncoding and coding regions based on their location. To study the functional implications of noncoding CHD-SNPs, we cross-validated them with enhancer-specific histone modification marks from developing human heart across 9 Carnegie stages and identified potential cardiac enhancers. This approach led to the identification of 2,056 CHD-associated putative enhancers (CHD-enhancers), 38.9% of them overlapping with known enhancers catalogued in human enhancer disease database. We identified heart-related transcription factor binding sites within these CHD-enhancers, offering insights into the impact of SNPs on TF binding. Conservation analysis further revealed that many of these CHD-enhancers were highly conserved across vertebrates, suggesting their evolutionary significance. Utilizing heart-specific expression quantitative trait loci data, we further identified a subset of 63 CHD-SNPs with regulatory potential distributed across various cardiac tissues. Concurrently, coding CHD-SNPs were represented as a protein interaction network and its subsequent binding energy analysis focused on a pair of proteins within this network, pinpointed a deleterious coding CHD-SNP, rs770030288, located in C2 domain of MYBPC3 protein. Overall, our findings demonstrate that SNPs have the potential to disrupt gene regulatory systems, either by affecting enhancer sequences or modulating protein-protein interactions, which can lead to abnormal developmental processes contributing to CHD pathogenesis.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"55"},"PeriodicalIF":3.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major F plasmid clusters are linked with ColV and pUTI89-like marker genes in bloodstream isolates of Escherichia coli.","authors":"Cameron J Reid, Max L Cummins, Steven P Djordjevic","doi":"10.1186/s12864-025-11226-4","DOIUrl":"10.1186/s12864-025-11226-4","url":null,"abstract":"<p><strong>Background: </strong>F plasmids are abundant in E. coli, carrying a variety of genetic cargo involved in fitness, pathogenicity, and antimicrobial resistance. ColV and pUTI89-like plasmids have drawn attention for their potential roles in various forms of extra-intestinal pathogenicity. However, the rates of their carriage and the overall diversity of F plasmids in E. coli bloodstream infections (BSI E. coli) remain unknown.</p><p><strong>Methods: </strong>We performed a t-SNE-based cluster analysis of predicted F plasmids from a collection of 4711 BSI E. coli draft genomes to describe their diversity and abundance. We also screened them for markers of ColV and pUTI89-like plasmids, F plasmid replicon sequence types (RST) and E. coli sequence types (ST) to understand how genetic features were related to plasmid clusters.</p><p><strong>Results: </strong>Predicted F plasmids in BSI E. coli draft genomes were embedded within five major clusters based on a model of complete F plasmid sequences. Nearly half of the clustered sequences belonged to two major clusters, which were associated with ColV and pUTI89-like marker genes, respectively. Genomes from the ColV cluster featured F2:A-:B1 and F24:A-B1 RSTs in association with ST95, ST58 and ST88, whilst the pUTI89-like cluster was mostly F29:A-:B10 linked to ST73, ST69, ST95 and ST131. Plasmids associated with different lineages of ST131 formed additional major clusters, whilst F51:A-:B10 plasmids in ST73 were also common.</p><p><strong>Conclusions: </strong>ColV and pUTI89-like plasmid markers are predominant in BSI E. coli that carry F plasmids. These markers are associated with distinct clusters of plasmids across diverse sequence types of E. coli. We hypothesise that their abundance in BSI E. coli is partially driven by carriage of backbone genes previously shown to contribute to virulence in models of bloodstream infection. Their carriage by pandemic E. coli STs suggests clonal expansion also plays a role in their success in BSI. Ecological pathways via which these plasmids evolve, and spread are likely to be distinct as other studies show ColV is strongly associated with poultry and food animal production, whereas pUTI89-like plasmids appear to be mostly human-restricted.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"57"},"PeriodicalIF":3.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}