BMC Genomics最新文献

{"title":"Maternal and offspring genome-wide association study of C-reactive protein reveals limited polygenic association with gestational diabetes mellitus.","authors":"Yu Zhang, Amy Moore, Kelli K Ryckman, Qi Yan, Rafael F Guerrero, Ming Li, Robert M Silver, Juhua Luo, Lynn M Yee, Uma M Reddy, Maisa N Feghali, Judith Chung, David M Haas, Kok Lim Kua, Nianjun Liu","doi":"10.1186/s12864-026-12878-6","DOIUrl":"10.1186/s12864-026-12878-6","url":null,"abstract":"<p><strong>Background: </strong>C-reactive protein (CRP) is a well-established biomarker of systemic inflammation. In pregnancy, several studies show association of elevated CRP with gestational diabetes mellitus (GDM). However, the genetic contributions of CRP levels during early pregnancy and their potential association with GDM remain largely understudied. The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) provides a unique opportunity to investigate these questions due to its rich design, including early pregnancy biospecimens, genome-wide genotype data, and detailed clinical outcomes across multiple ancestry groups.</p><p><strong>Results: </strong>We performed genome-wide association studies (GWAS) of first-trimester CRP levels using maternal (n = 4,326) and offspring (n = 2,140) genotypes from the nuMoM2b cohort. In the European-ancestry maternal sub-cohort of nuMoM2b, three genome-wide significant loci (CRP, LEPR, and HNF1A) were associated with early pregnancy CRP levels, consistent with findings from previous GWAS in non-pregnant populations. Analysis of the full multi-ancestry maternal cohort identified two additional loci (ENSG00000257703 and APOC1) associated with CRP levels. No genome-wide significant associations were detected in the offspring GWAS of CRP levels. Linkage disequilibrium score regression did not detect a significant genetic correlation between CRP and GDM using the nuMoM2b CRP GWAS. In contrast, a significant correlation was observed when using an external large population-based CRP GWAS, suggesting that genetic overlap between CRP and GDM may vary across study contexts. However, Polygenic risk scores for CRP derived from either GWAS source were not significantly associated with GDM risk in the nuMoM2b cohort.</p><p><strong>Conclusions: </strong>These findings provide insights into the genetic architecture of CRP levels during early pregnancy and illustrate the potential value of pregnancy-specific genomic studies for improving understanding of inflammatory processes relevant to maternal-fetal health. They also highlight the need for larger pregnancy cohorts to better understand the relationship between inflammation and metabolic complications during pregnancy.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"27 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036301","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":"Genetic structure analysis of Glycyrrhiza species and identification of SNP-loci associated with secondary metabolites in G. glabra.","authors":"Ali Moghadam, Akbar Karami, Beate Kellert, Reza Haghi, Hassan Esmaeili, Axel Himmelbach, Lars-Gernot Otto","doi":"10.1186/s12864-026-13361-y","DOIUrl":"10.1186/s12864-026-13361-y","url":null,"abstract":"<p><strong>Background: </strong>Glycyrrhiza spp. are medicinal legumes that produce a wide array of pharmacologically active secondary metabolites. This study generated a genomic resource by genotyping-by-sequencing 175 Glycyrrhiza accessions and populations to (1) characterize their genetic structure and assess population relationships, and (2) perform an association mapping for three medically important traits within G. glabra.</p><p><strong>Results: </strong>We identified 38,393 high-quality single-nucleotide polymorphisms (SNPs). Genetic structure analysis revealed that G. glabra is mostly distinct from the other species, and identified one group of 66 plants from 33 Iranian G. glabra origins with moderate genetic differentiation. The association mapping identified in total 20 highly significant SNPs for three traits: 15 for glabridin in the cork layer of the root, of which 3 were also associated with glabridin in the fleshy texture of the root, and 5 for liquiritigenin in the cork layer of the root. Glabridin and liquiritigenin are described to be involved in biotic and abiotic stress responses. Candidate genes include: (1) MYB6 - a transcription factor that activates flavonoid-biosynthetic genes. (2) OCTOPUS-like - a regulator of primary root protophloem differentiation and root architecture. (3) WRKY transcription factors - modulators of phenylpropanoid, alkaloid and terpene pathways. (4) Aminodeoxychorismate synthase.</p><p><strong>Conclusions: </strong>Our study provided a comprehensive understanding of the genetic diversity of Glycyrrhiza spp. We identified genetic markers associated with important metabolites of the root, i.e. the flavonoids glabridin and liquiritigenin. These findings will facilitate the exploitation of genetic resources and inform future breeding programs, ultimately contributing to the development of improved Glycyrrhiza spp. varieties with enhanced medicinal properties.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"27 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001305","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":"Comparative chloroplast genomics of Ajania sericea and sympatric Asteraceae species identifies shared candidate molecular features associated with alpine adaptation.","authors":"Hongting Yang, Siyu Wu, Qian He, Haoxi Xin, Wenmiao Li, Xi Chen","doi":"10.1186/s12864-026-13312-7","DOIUrl":"10.1186/s12864-026-13312-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ajania sericea is endemic to the Dali region of Yunnan and is currently the southernmost known member of the genus Ajania worldwide. It co-occurs with Aster brachytrichus, Anaphalis pannosa, and Leontopodium dedekensii in alpine habitats of northwestern Yunnan, where plants are exposed to strong ultraviolet radiation, low temperatures, strong winds, and drought. To explore whether sympatric Asteraceae species from different lineages share chloroplast genomic features associated with alpine response, we sequenced, assembled, and compared the chloroplast genomes of these four species.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;All four chloroplast genomes exhibited the typical quadripartite structure, with the highest GC content in the IR regions (42.99%-43.07%). A total of 142-145 gene copies were annotated. Ana. pannosa and L. dedekensii lacked ycf15, and Ana. pannosa further lacked trnT-GGU. Codon usage bias was generally weak, with preferred codons mainly ending in A/T, while neutrality and ENC-plot analyses suggested that factors other than mutational pressure, potentially including natural selection, may also contribute. Five hypervariable regions (petN, trnY-GUA, pafI-trnS-GGA, ndhC-trnV-UAC, and rpl32) were identified as potential candidate DNA barcode regions for Asteraceae. Phylogenetic analyses based on maximum likelihood and Bayesian inference yielded consistent topologies, and Aj. sericea was most closely related to Aj. nematoloba. Ka/Ks analysis indicated that most chloroplast protein-coding genes were under purifying selection, whereas only a few genes, including rpl14, rpl33, and rps2, showed relatively elevated Ka/Ks values or candidate selection signals. Integrated analyses of sequence variation, selection signals, and functional annotation suggested that rpl14, rpl33, petN, ndhC, and ndhF were mainly associated with chloroplast translation, photosynthetic electron transport, and redox regulation. In addition, the chloroplast genomes of three Aj. sericea samples collected at different elevations were highly similar, with no clear elevation-associated plastome differentiation detected.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study showed that the chloroplast genomes of four sympatric Asteraceae species were highly conserved in overall structure, but still exhibited certain differences in gene loss, IR boundary variation, repeat sequence composition, and local hypervariable regions. These features provide useful references for interspecific differentiation studies and the development of potential molecular markers in Asteraceae. No clear elevation-associated plastome differentiation was detected among the three Aj. sericea samples within the elevational range examined in this study. Overall, the candidate genes identified in this study, including rpl14, rpl33, petN, ndhC, and ndhF, suggest potentially shared molecular response features among sympatric Asteraceae species in alpine environments and provide new ch","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"27 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223251","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":"Enhancing detection of polygenic adaptation: a comparative study of machine learning and statistical approaches using simulated evolve-and-resequence data.","authors":"Cosima Caliendo, Susanne Gerber, Markus Pfenninger","doi":"10.1186/s12864-026-13163-2","DOIUrl":"10.1186/s12864-026-13163-2","url":null,"abstract":"<p><strong>Background: </strong>Detecting signals of polygenic adaptation remains a significant challenge in population genomics, as traditional methods often struggle to identify the associated subtle, multi-locus allele-frequency shifts. Here, we introduced and tested several novel approaches combining machine learning techniques with traditional statistical tests to detect polygenic adaptation patterns in time-series of allele frequency changes from whole genome data. We implemented a Naive Bayesian Classifier (NBC) and One-Class Support Vector Machines (OCSVM), and compared their performance against the classical Fisher's Exact Test (FET). Furthermore, we combined machine learning and statistical models (OCSVM-FET and NBC-FET), resulting in 5 competing approaches. The framework is mainly designed and validated for evolve-and-resequence (EaR) experimental designs, where defined selection pressures and temporal sampling are feasible, but might be applicable for certain natural experiments as well.</p><p><strong>Results: </strong>Using a simulated dataset based on empirical C. riparius Pool-Seq data, we evaluated methods across evolutionary scenarios varying in generation, selection strength, and number of loci under selection. Our results demonstrate that the combined OCSVM-FET approach consistently outperformed competing methods, achieving the lowest false positive rate, highest area under the curve, and high accuracy. The performance peak aligned with what we term the 'late dynamic phase' of adaptation - the period after initial selection has occurred but before fixation - highlighting the method's sensitivity to ongoing selective processes.</p><p><strong>Conclusions: </strong>Furthermore, we emphasize the critical role of parameter tuning, balancing biological assumptions with methodological rigor. While broader applicability remains an important direction for future work, the present benchmarking is intentionally scoped to EaR experimental contexts.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"27 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905066","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":"Correction: Differential roles of coding and non-coding transcripts in obesity: insights from RNA-seq analysis of Macaca fascicularis hepatocytes.","authors":"Yu Liu, Ziting Wang, Linna Liu, Ya Tan, Wenling Zheng, Pengfei Zhang, Andrew P Hutchins, Leonard Lipovich, Weizhong Wang","doi":"10.1186/s12864-026-13170-3","DOIUrl":"10.1186/s12864-026-13170-3","url":null,"abstract":"","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"27 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886126","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":"Transcriptomic analysis of eggs, rediae and cercariae reveal stage-specific adaptations in the rumen fluke Calicophoron daubneyi.","authors":"Leah R Knöpfle, Raúl O Cosentino, Markus R Schmidt, Verena K Elbert, Sandra Haug, Frank Weber, Antonio Vazquez Perera, T Nicolai Siegel, Markus Meissner","doi":"10.1186/s12864-026-13271-z","DOIUrl":"10.1186/s12864-026-13271-z","url":null,"abstract":"<p><p>Rumen flukes, particularly the trematode Calicophoron daubneyi, are emerging parasites of livestock in Europe, yet transcriptomic insights into their environmental and intermediate host stages remain limited. Here, we present a comprehensive transcriptomic analysis of eggs at three distinct developmental stages (freshly excreted, early developmental and eye-spot stages), as well as rediae and cercariae, of C. daubneyi. High-quality RNA-sequencing (RNA-seq) datasets revealed both shared and stage-specific transcriptional profiles with each developmental stage exhibiting its own distinct expression pattern. Subsequent GO-Term enrichment analyses revealed that fully embryonated eggs in eye-spot-stage especially upregulated genes related to cilia assembly, movement and motility, reflecting preparation for miracidial hatching and host-seeking behavior. Rediae showed enhanced transcription of genes involved in diverse metabolic and biosynthetic processes, supporting rapid asexual proliferation within the snail intermediate host. Cercariae exhibited predominant upregulation of genes associated with signal transduction and energy metabolism, indicating the adaptation to its changing environmental conditions. These findings provide the first transcriptomic insights into the biology of C. daubneyi outside the definitive host, reveal molecular mechanisms underlying development, transmission and adaptation to a changing environment and identify stage-specific genes as potential targets for interventions aimed at disrupting the parasites life cycle and controlling rumen flukes in the future.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"27 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879014","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":"From field to genome: non-lethal, on-site nanopore-only assembly of the endangered Grenada Frog (Pristimantis euphronides).","authors":"Katharina Kopp, Shelley Lownds, Billie Harrison, Heiner Kuhl, Sophie Moittié","doi":"10.1186/s12864-026-13291-9","DOIUrl":"10.1186/s12864-026-13291-9","url":null,"abstract":"<p><strong>Background: </strong>The genus Pristimantis is among the most species-rich vertebrate genera, with more than 600 described species, yet no whole-genome assembly was available for any member of the genus or for the families Strabomantidae or Craugastoridae prior to this work. The Grenada Frog (Pristimantis euphronides) is a critically endangered direct-developing anuran endemic to montane rainforest on Grenada in the Lesser Antilles. Reference genomes are foundational tools for the conservation of endangered species, but their production typically depends on destructive sampling, large institutional infrastructure, or the shipment of biomaterials abroad.</p><p><strong>Results: </strong>We present a 1.75 Gb scaffold-level reference genome of P. euphronides assembled from a single wild female sampled non-lethally by toe clip, blood swab, and buccal swab. All wet-laboratory steps, including Oxford Nanopore Technologies (ONT) MinION sequencing, were performed in-country on portable equipment, and downstream analyses ran on laptop-class hardware and a remote server accessed from Grenada. The Flye-Medaka assembly, scaffolded with RagTag against Eleutherodactylus coqui, comprised 13 pseudochromosomes with a scaffold N50 of 117.8 Mb, achieved 91.4% tetrapod BUSCO completeness, and supported 28,071 annotated protein-coding genes. Cross-species synteny analysis against three additional Hyloidea genomes computationally predicted an underlying karyotype of n = 16, consistent with prior cytogenetic counts, indicating that the reference-guided pseudochromosomes do not correspond to the true haploid chromosome number. Coverage analysis identified candidate Z-linked regions on two scaffolds and a set of unplaced contigs with sequence features consistent with the heterochromatic W chromosome described from C-banding, providing a first-pass framework for sex chromosome analyses in Pristimantis.</p><p><strong>Conclusions: </strong>This whole-genome assembly provides a reference for phylogenomic and conservation genomic studies in a hyperdiverse direct-developing frog clade in which previous comparative work had relied on few marker genes. In the absence of chromatin conformation capture methods such as Hi-C, which were not compatible with non-lethal field sampling, reference-guided scaffolding against the closest available chromosome-scale Hyloidea genome, approximately 52 million years divergent, provided a workable alternative. The non-lethal, in-country, ONT-only workflow demonstrates that scaffold-level reference genomes for repeat-rich vertebrates of conservation concern can be produced without destructive sampling or outsourcing to external sequencing or bioinformatics services.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"27 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079546","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":"Digestive tract morphology and metallocarboxypeptidase M14 gene family divergence associated with trophic niche differentiation in Odontodactylus japonicus, Lysiosquilla sulcirostris and Oratosquilla oratoria.","authors":"Fangrui Lou, Jiantong Zhang, Xiaowen Duan, Qi Huang","doi":"10.1186/s12864-026-13292-8","DOIUrl":"10.1186/s12864-026-13292-8","url":null,"abstract":"<p><strong>Background: </strong>Stomatopods may have evolved divergent trophic niches during adaptive radiation, yet the morphological and molecular bases underlying this diversification remain poorly understood. Here, we integrated multi-level microscopic observations with full-length (FL) transcriptome data to compare digestive-tract morphology and metallocarboxypeptidase M14 (MCP M14) characteristics among Odontodactylus japonicus, Lysiosquilla sulcirostris and Oratosquilla oratoria. The FL transcriptome of L. sulcirostris was newly generated in this study, whereas those of O. japonicus and O. oratoria were obtained from previously published datasets.</p><p><strong>Results: </strong>Pronounced interspecific differences were observed in digestive morphology. O. oratoria exhibited the highest density of cardiac-stomach setae and the narrowest gland-filter pores, whereas L. sulcirostris had the thickest cardiac-stomach wall and chitin layer and the most developed pyloric muscular layer. In contrast, O. japonicus showed the greatest hindgut villus height and hepatopancreas index. Using the newly generated FL transcriptome of L. sulcirostris and previously published datasets for O. japonicus and O. oratoria, we identified 45 MCP M14 sequences in O. japonicus, 26 in L. sulcirostris and 15 in O. oratoria. MCP M14 sequences from O. japonicus and L. sulcirostris were assigned to the M14A, M14B and M14D subfamilies, whereas only M14A sequences were detected in O. oratoria. Conserved-motif and sequence analyses indicated overall structural conservation but substantial variation in subfamily composition and canonical catalytic residues. Integrative analysis further revealed distinct morphological-molecular profiles, with O. japonicus showing greater hindgut villus development and a broader detected MCP M14 repertoire, L. sulcirostris displaying greater specialization in mechanical food processing, and O. oratoria exhibiting more pronounced filtration-related traits.</p><p><strong>Conclusion: </strong>These findings indicate that digestive adaptation among the three stomatopods is associated with distinct combinations of digestive morphology and MCP M14 characteristics rather than uniform changes across the digestive system. Such contrasting morphological-molecular configurations provide an integrated basis for understanding trophic niche differentiation in stomatopods.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"27 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134994","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":"scGPA: an LLM-assisted workflow for directional virtual gene perturbation analysis from single-cell transcriptomes.","authors":"Haijun Tang, Hening Li, Qinghao Zhao, Xiang Zhou, Lei Peng, Yangjie Cai, Rongzhen Lin, Yufeng Li, Yiyi Yuan, Wenyu Feng, Yun Liu, Zezheng Liu, Qingchu Li","doi":"10.1186/s12864-026-13270-0","DOIUrl":"10.1186/s12864-026-13270-0","url":null,"abstract":"<p><strong>Background: </strong>Existing virtual perturbation methods can often infer directional changes by comparing predicted post-perturbation expression profiles with control cells. However, workflows that directly return direction-specific downstream candidate genes together with confidence scores, evidence support and interpretable summaries remain limited. We developed scGPA, an LLM-assisted workflow system for directional single-cell virtual gene perturbation analysis.</p><p><strong>Methods: </strong>scGPA starts from raw single-cell RNA sequencing data and performs quality control, normalization, dimensionality reduction, clustering and cell-group selection. It then constructs cell-group-specific wild-type regulatory networks using repeated subsampling, principal component regression (PCR)/Ridge-based network inference and CP tensor denoising. Based on these networks, scGPA simulates dose-aware virtual knockdown of the target gene and applies signed perturbation propagation to estimate the magnitude and direction of downstream transcriptional responses. LLM assistance is used for marker-based cell-type annotation, evidence-guided candidate prioritization and user-facing biological summarization.</p><p><strong>Results: </strong>We benchmarked scGPA across five public Perturb-seq datasets and compared its performance with GEARS, scGPT and a random baseline. The overall correct prediction rate of scGPA was 23.0%, exceeding those of GEARS (20.7%), scGPT (15.1%) and the random baseline (13.6%). These results indicate that scGPA achieved a higher correct prediction rate than the two comparator models and the random baseline. We subsequently evaluated scGPA using a public osteosarcoma single-cell dataset and performed qRT-PCR validation in 143B osteosarcoma cells. Among genes with significant experimental changes, scGPA achieved a directional concordance of 76.9%. When all tested downstream genes were counted, 37.0% were directionally correct, 51.9% showed no significant change and 11.1% changed in the opposite direction.</p><p><strong>Conclusions: </strong>scGPA provides a practical workflow system for predicting and prioritizing direction-specific downstream transcriptional responses after target-gene perturbation. By integrating single-cell regulatory network inference, signed virtual perturbation and LLM-assisted interpretation, scGPA supports target-gene function inference and downstream mechanistic investigation from single-cell transcriptomic data.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"27 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987984","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":"Integrating deep learning and pangenomics to recover missing heritability from wild structural variations.","authors":"Yiquan Wang, Minnuo Cai, Yahui Ma, Aurélien Tellier, Kai Wei","doi":"10.1186/s12864-026-13274-w","DOIUrl":"10.1186/s12864-026-13274-w","url":null,"abstract":"<p><p>Crop domestication has induced a severe genetic bottleneck that reduces the adaptive diversity present in modern cultivars. Standard intra-population genomic prediction models reliant on linear reference genomes and SNPs fail to capture the full spectrum of phenotypic variance hidden in wild relatives. Realizing this potential requires broadening the predictive paradigm from selection within narrow breeding populations toward evolutionary-scale inference across the entire wild-to-cultivated continuum. This missing heritability is largely sequestered within complex structural variations such as presence-absence and copy number variants. These variations drive environmental adaptations but remain obscured by reference bias. To recover these unmapped structural variations the field is evolving from linear coordinates to high-dimensional genomic data representations. We review this transition by contrasting explicit graph topologies that map reticulate evolution with implicit encodings like K-mers that capture sequence composition independent of alignment. Processing these complex and high-dimensional features necessitates advanced computational tools. We synthesize emerging deep learning frameworks and highlight how Graph Neural Networks resolve inheritance paths in topological data while Transformer-based foundation models extract functional syntax from sequence context. These architectures effectively integrate structural variations to resolve non-additive effects such as epistasis missed by traditional models. Computing these hidden structural variations facilitates the precise utilization of wild germplasm. We demonstrate how AI-driven strategies enable zero-shot prediction for uncharacterized wild alleles and optimize genotype-by-environment interactions. Ultimately these approaches pave the way for accelerated de novo domestication of climate-resilient crops.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"27 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787776","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}