BMC BiologyPub Date : 2025-08-01DOI: 10.1186/s12915-025-02351-3
Jungeun Kim, Asta Blazyte, Jae-Pil Choi, Changjae Kim, Fedor Sharko, Sungwon Jeon, Eun-Mi Kim, Hawsun Sohn, Jong Hee Lee, Hyun Woo Kim, Mi Hyun Yoo, Kyunglee Lee, Artem Nedoluzhko, Jong Bhak
{"title":"Dokdo sea lion Zalophus japonicus genome reveals its evolutionary trajectory before extinction.","authors":"Jungeun Kim, Asta Blazyte, Jae-Pil Choi, Changjae Kim, Fedor Sharko, Sungwon Jeon, Eun-Mi Kim, Hawsun Sohn, Jong Hee Lee, Hyun Woo Kim, Mi Hyun Yoo, Kyunglee Lee, Artem Nedoluzhko, Jong Bhak","doi":"10.1186/s12915-025-02351-3","DOIUrl":"10.1186/s12915-025-02351-3","url":null,"abstract":"<p><strong>Background: </strong>The Dokdo sea lion (Zalophus japonicus), commonly referred to as Gangchi in Korea and the Japanese sea lion internationally, was endemic to the Northwest Pacific before its extinction in the 1950s. However, its origins, speciation, and genetic diversity remain poorly understood.</p><p><strong>Results: </strong>To address this, we sequenced DNA from 16 Z. japonicus bone fragments, obtained from Dokdo and Ulleungdo islands in Korea. Our genome-wide SNP analyses reveal Z. japonicus as the earliest diverged species within its genus, redefining its evolutionary relationship with the California (Z. californianus) and Galapagos (Z. wollebaeki) sea lions. Our research further elucidates the phylogeny of Z. japonicus, shedding light on the complexity of the genetic isolation process within its genus that was prompted by the geographic isolation of the three populations of Zalophus ancestral stock. Conversely, the genetic signature of the Dokdo sea lion genome can be modeled as an evolutionary pathway involving gene flow from Otariidae species with shared range. In addition, we discovered that the population decline of Z. japonicus started already over 100,000 years ago; however, Z. japonicus genome maintained a relatively high heterozygosity despite nearing extinction.</p><p><strong>Conclusions: </strong>Our genome-scale analysis sheds light on the phylogeny of Z. japonicus, the evolutionary pathways underlying its speciation, and its genetic diversity before extinction. Broadly, we elucidate Zalophus gene flow complexity and genetic diversities among extant species. Furthermore, this study offers retrospective genomic insights into the extinction process of a carnivorous marine mammal, information that could aid conservation efforts for extant Otariidae species.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"234"},"PeriodicalIF":4.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC BiologyPub Date : 2025-07-31DOI: 10.1186/s12915-025-02347-z
Lezheng Yu, Yuxin Luo, Shiqi Wu, Siyi Chen, Li Xue, Runyu Jing, Jiesi Luo
{"title":"Multimodal deep learning for allergenic proteins prediction.","authors":"Lezheng Yu, Yuxin Luo, Shiqi Wu, Siyi Chen, Li Xue, Runyu Jing, Jiesi Luo","doi":"10.1186/s12915-025-02347-z","DOIUrl":"10.1186/s12915-025-02347-z","url":null,"abstract":"<p><strong>Background: </strong>Accurate prediction of allergens is essential for identifying the sources of allergic reactions and preventing future exposure to harmful triggers; however, the limited performance of current prediction tools hinders their practical applications.</p><p><strong>Results: </strong>Here, we present Multimodal-AlgPro, a unified framework based on a multimodal deep learning algorithm designed to predict allergens by integrating multiple dimensions, including physicochemical properties, amino acid sequences, and evolutionary information. An exhaustive search strategy for model combinations has also been introduced to ensure robust allergen prediction by thoroughly exploring every possible modality configuration to determine the most effective framework architecture. Additionally, identifying explainable sequence motifs and molecular descriptors from these models that facilitate epitope discovery is of interest. Because it leverages diverse heterogeneous features and our improved multimodal data fusion, Multimodal-AlgPro outperformed several existing methods, demonstrating its potential to significantly advance the accuracy of allergen prediction.</p><p><strong>Conclusions: </strong>Overall, Multimodal-AlgPro is a valuable tool for deciphering the mechanisms of allergic responses and offers novel insights on epitope design, with applications in both public health and industrial sectors.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"232"},"PeriodicalIF":4.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC BiologyPub Date : 2025-07-31DOI: 10.1186/s12915-025-02345-1
Jana Koch, Alessandra Ruggia, Carina Beha, Irina Wipf, Damir Zhakparov, Patrick Westermann, Svenja Schmelzer, Anja Heider, Klemens Fröhlich, Katja Baerenfaller
{"title":"Uncovering protein prenylation in Th1 cells: novel prenylation sites and insights into statin and farnesyltransferase inhibition.","authors":"Jana Koch, Alessandra Ruggia, Carina Beha, Irina Wipf, Damir Zhakparov, Patrick Westermann, Svenja Schmelzer, Anja Heider, Klemens Fröhlich, Katja Baerenfaller","doi":"10.1186/s12915-025-02345-1","DOIUrl":"10.1186/s12915-025-02345-1","url":null,"abstract":"<p><strong>Background: </strong>T helper 1 (Th1) cell activation is an essential process for immune responses and is tightly regulated, including the prenylation of proteins critical for T cell function. Prenylation facilitates membrane association and protein function and, according to current consensus, is confined to C-terminal prenylation motifs. However, the full extent of the prenylated proteome, a broader understanding of prenylation sites, and the effects of inhibiting prenylation or blocking isoprenoid synthesis using statins remain incompletely understood. To address these gaps, we aimed to comprehensively identify and characterise protein prenylation in Th1 cells.</p><p><strong>Results: </strong>Using a click chemistry-based enrichment approach followed by mass spectrometry in primary in vitro-differentiated Th1 cells, we identified both known and novel prenylated proteins, some of which exhibited differential prenylation during Th1 cell activation, highlighting the dynamic nature of the Th1 prenylome. Characterisation of these proteins revealed isoform-specific prenylation, novel C-terminal prenylation motifs, and a structural motif associated with internal prenylation. Furthermore, statin treatment influenced the Th1 prenylome, altering protein prenylation in a prenyltransferase-dependent manner, underscoring distinct enzymatic specificities and potential off-target effects.</p><p><strong>Conclusions: </strong>Our findings confirm that prenylation plays a key role in Th1 cell function, with more proteins undergoing prenylation than previously known, some of which exhibit activation-dependent changes. The identification of non-canonical prenylation events challenges current views on prenylation, expanding the repertoire of modification sites. Together, our molecular insights into protein prenylation in Th1 cells and the effects of prenyltransferase inhibition and statin treatment have important implications for therapeutic strategies targeting immune regulation.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"233"},"PeriodicalIF":4.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NR1I3 modulates Wnt signaling to promote anterior-posterior axis patterning.","authors":"Yujia Sun, Ning Ding, Shuqi Li, Yuan Zhang, Yunfei Qin, Zhitai Hao, Shoutao Zhang, Qingnan Tian","doi":"10.1186/s12915-025-02346-0","DOIUrl":"10.1186/s12915-025-02346-0","url":null,"abstract":"<p><strong>Background: </strong>Regeneration of missing structures and tissue turnover during homeostasis require positional information to instruct the reestablishment of body axes and to specify new cells to replace aged tissues. Planarians present an ideal model for positional information studies, as they can regenerate any missing parts and replace aged cells during tissue turnover. Position control genes (PCGs) characterized by constitutive and regional expression in planarians have been identified to instruct regeneration and tissue turnover. However, it is not entirely understood how these genes coordinate in maintaining proper tissue structures.</p><p><strong>Results: </strong>Here we report that NR1I3, a nuclear receptor family transcription factor, functions in the establishment and maintenance of the anteroposterior (AP) axis in planarians. NR1I3 RNA interference (RNAi) during regeneration caused ectopic head formation in the posterior blastema, correlated with symmetric notum expression at wounds. Loss of NR1I3 function in intact planarians resulted in ectopic anterior eye formation and the absence or reduction of posterior PCG expression. Notably, the phenotype of two-headed planarians after NR1I3 RNAi can be suppressed by APC, axins, and notum, which are components of the Wnt signaling.</p><p><strong>Conclusions: </strong>Our data reveal that NR1I3 in planarians acts as an upstream regulator of Wnt signaling, mediating AP patterning through regulating the activation of notum.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"231"},"PeriodicalIF":4.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CanCellCap: robust cancer cell capture across tissue types on single-cell RNA-seq data by multi-domain learning.","authors":"Jiaxing Bai, Yichun Gao, Feng Zhou, Yushuang He, Chen Lin, Xiaobing Huang, Ying Wang","doi":"10.1186/s12915-025-02337-1","DOIUrl":"10.1186/s12915-025-02337-1","url":null,"abstract":"<p><strong>Background: </strong>The advent of single-cell RNA sequencing (scRNA-seq) has provided unprecedented insights into cancer cellular diversity, enabling a comprehensive understanding of cancer at the single-cell level. However, identifying cancer cells remains challenging due to gene expression variability caused by tumor or tissue heterogeneity, which negatively impacts generalization and robustness.</p><p><strong>Results: </strong>We propose CanCellCap, a multi-domain learning framework, to identify cancer cells in scRNA-seq data suitable for all tissues, cancers, and sequencing platforms. Integrating domain adversarial learning and Mixture of Experts, CanCellCap is able to simultaneously extract common and specific patterns in gene expression profiles across different tissues for cancer or normal cells. Moreover, the masking-reconstruction strategy enables CanCellCap to cope with scRNA-seq data from different sequencing platforms. CanCellCap achieves 0.977 average accuracy in cancer cell identification across 13 tissue types, 23 cancer types, and 7 sequencing platforms. It outperforms five state-of-the-art methods on 33 benchmark datasets. Notably, CanCellCap maintains high performance on unseen cancer types, tissue types, and even across species, highlighting its effectiveness in challenging scenarios. It also excels in spatial transcriptomics by accurately identifying cancer spots. Furthermore, CanCellCap demonstrates strong computational efficiency, completing inference on 100,000 cells in a few minutes. In addition, interpretability analyses reveal critical biomarkers and pathways, offering valuable biological insights.</p><p><strong>Conclusions: </strong>CanCellCap provides a robust and accurate framework for identifying cancer cells across diverse platforms, tissue types, and cancer types. Its strong generalization to unseen cancers, tissues, and even species, combined with its adaptability to spatial transcriptomics data, underscores its versatility for both research and clinical applications.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"230"},"PeriodicalIF":4.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting the complement-mTOR-autophagy axis: the role of apolipoprotein E in depression.","authors":"Yong Li, Chengyuan Xu, Jing Liu, Mengru Guo, Jia Wang, Xianbing Bai, Yujie Cheng, Xinyue Luan, Huailong Pei, Chenlei Zhang, Huan Liu, Ming Chen, Binliang Tang","doi":"10.1186/s12915-025-02301-z","DOIUrl":"10.1186/s12915-025-02301-z","url":null,"abstract":"<p><strong>Background: </strong>Depression is a highly prevalent and debilitating psychiatric disorder, and while Apolipoprotein E (ApoE), a critical regulator of lipid transport and neuronal function, has been implicated in regulating depressive behaviors, the underlying mechanisms remain insufficiently understood.</p><p><strong>Results: </strong>In this study, we explored the role of ApoE in depression using complementary animal models. We observed significantly reduced ApoE levels in the hippocampus of both chronic social defeat stress (CSDS) and lipopolysaccharide (LPS)-induced depression models, with ApoE knockout (ApoE<sup>-/-</sup>) mice exhibiting exacerbated depressive-like behaviors. Hippocampal ApoE overexpression effectively reversed these behavioral deficits, demonstrating ApoE's essential role in modulating depressive-like behaviors. Mechanistically, ApoE knockout triggered microglial hyperactivation and complement C3 elevation, leading to sustained mTOR pathway activation and subsequent impairment of autophagy. The critical role of this pathway was validated through pharmacological intervention, where treatment with the mTOR inhibitor rapamycin restored autophagy, reduced neuroinflammation, and alleviated depressive behaviors.</p><p><strong>Conclusions: </strong>These findings demonstrate that ApoE regulates depressive behaviors by modulating the complement-mTOR-autophagy axis, identifying multiple potential therapeutic targets for clinical intervention in depression.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"228"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC BiologyPub Date : 2025-07-28DOI: 10.1186/s12915-025-02334-4
Moritz Baur, Nora K E Schulz, Lilo Greune, Zoe M Länger, Jürgen Eirich, Iris Finkemeier, Robert Peuß, Petra Dersch, Joachim Kurtz
{"title":"Immune priming in the insect gut: a dynamic response revealed by ultrastructural and transcriptomic changes.","authors":"Moritz Baur, Nora K E Schulz, Lilo Greune, Zoe M Länger, Jürgen Eirich, Iris Finkemeier, Robert Peuß, Petra Dersch, Joachim Kurtz","doi":"10.1186/s12915-025-02334-4","DOIUrl":"10.1186/s12915-025-02334-4","url":null,"abstract":"<p><strong>Background: </strong>Research on forms of memory in innate immune systems has recently gained momentum with the study of trained immunity in vertebrates and immune priming in invertebrates. Immune priming is an evolutionary ancient process that confers protection against previously encountered pathogens. However, despite the existence of immune priming across many invertebrate taxa, evolution and mechanisms of immune priming are still not well understood. Moreover, it is unclear how natural pathogens might elicit immune priming in their hosts.</p><p><strong>Results: </strong>Here we combine RNA sequencing with transmission electron microscopy to investigate the dynamic processes during priming in the gut of a well-established model for oral immune priming, consisting of the host Tribolium castaneum and its natural pathogen Bacillus thuringiensis tenebrionis (Btt). We show that priming with specific, pathogen-derived virulence-relevant factors induces gut damage in T. castaneum larvae, triggering an early physiological stress response and upregulation of a distinct set of immune genes. This response diminishes over time yet enables the gut to upregulate genes known to interfere with Btt virulence when later exposed to infectious Btt spores.</p><p><strong>Conclusions: </strong>Our findings demonstrate that pathogen-derived factors inducing gut damage and stress responses prime gut tissue to provide more efficient protection against infection. These insights deepen our understanding of the mechanisms driving innate immune memory, which likely evolved as an adaptive response to natural pathogens.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"227"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DTI-RME: a robust and multi-kernel ensemble approach for drug-target interaction prediction.","authors":"Yuqing Qian, Xin Zhang, Yizheng Wang, Quan Zou, Chen Cao, Yijie Ding, Xiaoyi Guo","doi":"10.1186/s12915-025-02340-6","DOIUrl":"10.1186/s12915-025-02340-6","url":null,"abstract":"<p><strong>Background: </strong>Drug-target interaction (DTI) refers to the specific mechanisms by which drug molecules interact with biological targets within a biological system. Computational methods are widely employed for DTI prediction, as they are time-efficient and resource-saving compared to experimental approaches. Although numerous DTI prediction methods have achieved promising results, accurately modeling DTIs remains challenging due to three key issues: noisy interaction labels, ineffective multi-view fusion, and incomplete structural modeling.</p><p><strong>Results: </strong>We propose a novel method termed DTI-RME. The DTI-RME introduces an innovative <math> <mrow><msub><mi>L</mi> <mn>2</mn></msub> <mo>-</mo> <mi>C</mi></mrow> </math> loss function that combines the benefits of <math><msub><mi>L</mi> <mn>2</mn></msub> </math> loss to reduce prediction errors and the robustness of C-loss in handling outliers. This method fuses multiple views through multi-kernel learning that assigns weights to different kernels. DTI-RME uses ensemble learning to assume and learn multiple structures, including the drug-target pair, drug, target, and low-rank structures.</p><p><strong>Conclusions: </strong>We evaluated DTI-RME on five real-world DTI datasets and conducted experiments focusing on three key scenarios. In all experiments, DTI-RME demonstrated superior performance compared to existing methods. Furthermore, the case study confirmed DTI-RME's ability to identify novel drug-target interactions accurately, with 17 of the top 50 predicted interactions being validated.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"225"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC BiologyPub Date : 2025-07-28DOI: 10.1186/s12915-025-02325-5
Elodie Couderc, Anna B Crist, Josquin Daron, Hugo Varet, Femke A H van Hout, Pascal Miesen, Umberto Palatini, Stéphanie Dabo, Thomas Vial, Louis Lambrechts, Sarah H Merkling
{"title":"Aedes aegypti VLG-1 challenges the assumed antiviral nature of Vago genes.","authors":"Elodie Couderc, Anna B Crist, Josquin Daron, Hugo Varet, Femke A H van Hout, Pascal Miesen, Umberto Palatini, Stéphanie Dabo, Thomas Vial, Louis Lambrechts, Sarah H Merkling","doi":"10.1186/s12915-025-02325-5","DOIUrl":"10.1186/s12915-025-02325-5","url":null,"abstract":"<p><strong>Background: </strong>Arthropod-borne viruses (arboviruses) such as dengue virus (DENV) and Zika virus (ZIKV) pose a significant threat to global health. Novel approaches to control the spread of arboviruses focus on harnessing the antiviral immune system of their primary vector, the Aedes aegypti mosquito. In arthropods, genes of the Vago family are often presented as analogs of mammalian cytokines with potential antiviral functions, but the role of Vago genes upon virus infection in Ae. aegypti is largely unknown.</p><p><strong>Results: </strong>We conducted a phylogenetic analysis of the Vago gene family in Diptera, which led us to focus on a Vago-like gene that we named VLG-1. Using CRISPR/Cas9-mediated gene editing, we generated a VLG-1 mutant line of Ae. aegypti, which revealed a broad impact of VLG-1 on the mosquito transcriptome, affecting several biological processes potentially related to viral replication, including the oxidative stress response. Surprisingly, experimental viral challenge of the VLG-1 mutant line indicated a modest proviral role for this gene during DENV and ZIKV infections in vivo. In the absence of VLG-1, virus dissemination throughout the mosquito's body was slightly impaired, albeit not altering virus transmission rates.</p><p><strong>Conclusions: </strong>Our results challenge the conventional understanding of Vago-like genes as antiviral factors and underscore the need for further in vivo research to elucidate the molecular mechanisms underlying mosquito-arbovirus interactions.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"223"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMC BiologyPub Date : 2025-07-28DOI: 10.1186/s12915-025-02328-2
Md Nafis Ul Alam, Cristian Román-Palacios, Dario Copetti, Rod A Wing
{"title":"Universal orthologs infer deep phylogenies and improve genome quality assessments.","authors":"Md Nafis Ul Alam, Cristian Román-Palacios, Dario Copetti, Rod A Wing","doi":"10.1186/s12915-025-02328-2","DOIUrl":"10.1186/s12915-025-02328-2","url":null,"abstract":"<p><strong>Background: </strong>Universal single-copy orthologs are the most conserved components of genomes. Although they are routinely used for studying evolutionary histories and assessing new assemblies, current methods do not incorporate information from available genomic data.</p><p><strong>Results: </strong>Here, we first determine the influence of evolutionary history on universal gene content and find that across 11,098 genomes of plants, fungi, and animals comprising 2606 taxonomic groups, 215 groups significantly vary from their respective lineages in terms of BUSCO (Benchmarking Universal Single Copy Orthologs) completeness. Additionally, 169 groups display an elevated complement of duplicated orthologs, likely from ancestral whole genome duplication events. Secondly, we investigate the extent of taxonomic congruence in broad BUSCO-derived phylogenies. For 275 suitable families out of 543 tested, sites evolving at higher rates produce at most 23.84% more taxonomically concordant, and at least 46.15% less terminally variable phylogenies compared to lower-rate sites. We find that BUSCO concatenated and coalescent trees have comparable accuracy and conclude that higher rate sites from concatenated alignments produce the most congruent and least variable phylogenies. Finally, we show that undetected, yet pervasive BUSCO gene loss events lead to misrepresentations of assembly quality. To overcome this, we filter a Curated set of BUSCOs (CUSCOs) that provide up to 6.99% fewer false positives compared to the standard search and introduce novel methods for comparing assemblies using gene synteny.</p><p><strong>Conclusions: </strong>Overall, we highlight the importance of considering evolutionary histories during assembly evaluations and release the phyca software toolkit that reconstructs consistent phylogenies and offers more precise assembly assessments.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"224"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}