{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:51:45Z","timestamp":1793145105034,"version":"4.5.0"},"reference-count":38,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2021YFD1600401"],"award-info":[{"award-number":["2021YFD1600401"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Core Technology Research and Development in Shaanxi Province Agriculture","award":["2026NYGG010"],"award-info":[{"award-number":["2026NYGG010"]}]},{"name":"Key Core Technology Research and Development in Shaanxi Province Agriculture","award":["2025NYGG010"],"award-info":[{"award-number":["2025NYGG010"]}]},{"name":"Undergraduate Innovation Fund of Northwest A&F University, China","award":["XN 2026025148"],"award-info":[{"award-number":["XN 2026025148"]}]},{"award":["XN 2026025148"],"award-info":[{"award-number":["XN 2026025148"]}],"id":[{"id":"https:\/\/ror.org\/0051rme32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Buchwaldoboletus xylophilus is a rare saprotrophic edible mushroom in the Boletaceae and is the second bolete species to have been successfully cultivated artificially, yet its developmental molecular regulation remains unexplored. We integrated RNA-seq transcriptomics and untargeted LC-MS\/MS metabolomics across five developmental stages (A\u2013E), applying differential expression, alternative splicing, ceRNA network construction, WGCNA, machine learning, consensus clustering, and O2PLS joint modelling. Transcriptomic analysis revealed that the mycelium-to-primordium transition (stage A to C) showed the most drastic reprogramming, with 2233 differentially expressed genes, while metabolomic comparison between stage A and E revealed overwhelmingly upregulated metabolites (184 up vs. 10 down), indicating asymmetric regulation between the two omics layers. Notably, mutually exclusive exon splicing events exhibited high functional significance, and all top ceRNA hubs were lncRNAs. Unsupervised consensus clustering validated the molecular distinctness of the sampled stages. Metabolite enrichment highlighted antioxidant functions and ABC transporter pathways, and O2PLS integrative modelling confirmed a strong shared developmental signal between transcriptome and metabolome. This study provides the first multidimensional molecular atlas for B. xylophilus, revealing a non-linear developmental programme, transcriptome\u2013metabolome decoupling, and a central role of antioxidant defence throughout development. Our findings offer mechanistic clues regarding the evolutionary transition from ectomycorrhizal to saprotrophic lifestyles in the Boletaceae and establish a multi-omics foundation for the molecular breeding of this emerging edible and medicinal mushroom.<\/jats:p>","DOI":"10.3390\/biology15161343","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:20:03Z","timestamp":1786324803000},"page":"1343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated Multi-Omics Reveals the Developmental Programs and Metabolic Regulation of the Rare Edible Fungus Buchwaldoboletus xylophilus"],"prefix":"10.3390","volume":"15","author":[{"given":"Yuying","family":"Liu","sequence":"first","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"},{"name":"Center of Edible Fungi, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Jia","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Yangling Zhijun Fungi Biotechnology Engineering Co., Ltd., Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"},{"name":"Center of Edible Fungi, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiao","family":"Song","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"},{"name":"Center of Edible Fungi, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"},{"name":"Center of Edible Fungi, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Wan","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Shaanxi Agriculture and Forestry Technology University, Yangling, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoyin","family":"Shen","sequence":"additional","affiliation":[{"name":"Yangling Zhijun Fungi Biotechnology Engineering Co., Ltd., Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglei","family":"Li","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"},{"name":"Center of Edible Fungi, Northwest A&F University, Yangling, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1418-873X","authenticated-orcid":false,"given":"Jianzhao","family":"Qi","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Xianyang 712100, China"},{"name":"Center of Edible Fungi, Northwest A&F University, Yangling, Xianyang 712100, China"},{"name":"Yangling Zhijun Fungi Biotechnology Engineering Co., Ltd., Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s13225-016-0375-8","article-title":"One hundred noteworthy boletes from China","volume":"81","author":"Wu","year":"2016","journal-title":"Fungal Divers."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109348","DOI":"10.1016\/j.fbio.2026.109348","article-title":"Multi-omics integrated analysis provides insights into developmental mechanisms, metabolic variations and key component biosynthesis in the rare medicinal fungus Gerronema lapidescens","volume":"82","author":"Jia","year":"2026","journal-title":"Food Biosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1111\/nph.17858","article-title":"Evolutionary innovations through gain and loss of genes in the ectomycorrhizal Boletales","volume":"233","author":"Wu","year":"2022","journal-title":"New Phytol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3897\/mycokeys.124.165901","article-title":"The subfamily Chalciporoideae (Boletaceae, Boletales) in China","volume":"124","author":"Zhang","year":"2025","journal-title":"MycoKeys"},{"key":"ref_5","first-page":"1","article-title":"A preliminary survey of the genus Buchwaldoboletus (Boletaceae: Boletales)","volume":"40","author":"Both","year":"2011","journal-title":"Bull. Buffalo Soc. Nat. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"137","DOI":"10.11646\/phytotaxa.520.2.2","article-title":"Buchwaldoboletus xylophilus and Phlebopus portentosus, two non-ectomycorrhizal boletes from tropical China","volume":"520","author":"Xie","year":"2021","journal-title":"Phytotaxa"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"W435","DOI":"10.1093\/nar\/gkl200","article-title":"AUGUSTUS: Ab initio prediction of alternative transcripts","volume":"34","author":"Stanke","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_8","unstructured":"Andrews, S. (2010). FastQC: A Quality Control Tool for High Throughput Sequence Data, Babraham Bioinformatics, Babraham Institute."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_11","unstructured":"Team, R.C. (2024). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E5593","DOI":"10.1073\/pnas.1419161111","article-title":"rMATS: Robust and flexible detection of differential alternative splicing from replicate RNA-Seq data","volume":"111","author":"Shen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","first-page":"1803","article-title":"REDItools: High-throughput RNA editing detection made easy","volume":"31","author":"Picardi","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"W49","DOI":"10.1093\/nar\/gky316","article-title":"psRNATarget: A plant small RNA target analysis server (2017 release)","volume":"46","author":"Dai","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_16","first-page":"1","article-title":"The igraph software package for complex network research","volume":"1695","author":"Csardi","year":"2006","journal-title":"Comput. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building predictive models in R using the caret package","volume":"28","author":"Kuhn","year":"2008","journal-title":"J. Stat. Softw."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Chen, T., and Guestrin, C. (2016). XGBoost: A scalable tree boosting system. Proceedings of the KDD \u201816: 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, San Francisco, CA, USA, 13\u201317 August 2016, Association for Computing Machinery.","DOI":"10.1145\/2939672.2939785"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1093\/bioinformatics\/btq170","article-title":"ConsensusClusterPlus: A class discovery tool with confidence assessments and item tracking","volume":"26","author":"Wilkerson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"D309","DOI":"10.1093\/nar\/gky1085","article-title":"eggNOG 5.0: A hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00104","DOI":"10.1128\/mmbr.00104-22","article-title":"The role of chromatin and transcriptional control in the formation of sexual fruiting bodies in fungi","volume":"86","author":"Nowrousian","year":"2022","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6179","DOI":"10.1007\/s00253-023-12726-7","article-title":"Transcription factors: Switches for regulating growth and development in macrofungi","volume":"107","author":"Sun","year":"2023","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). Ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/nbt.2377","article-title":"A cross-platform toolkit for mass spectrometry and proteomics","volume":"30","author":"Chambers","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","article-title":"Proposed minimum reporting standards for chemical analysis: Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI)","volume":"3","author":"Sumner","year":"2007","journal-title":"Metabolomics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/nbt.3597","article-title":"Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking","volume":"34","author":"Wang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/jms.1777","article-title":"MassBank: A public repository for sharing mass spectral data for life sciences","volume":"45","author":"Horai","year":"2010","journal-title":"J. Mass Spectrom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D608","DOI":"10.1093\/nar\/gkx1089","article-title":"HMDB 4.0: The human metabolome database for 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/nmeth.2551","article-title":"LipidBlast in silico tandem mass spectrometry database for lipid identification","volume":"10","author":"Kind","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11306-016-1030-9","article-title":"Non-targeted UHPLC-MS metabolomic data processing methods: A comparative investigation of normalisation, missing value imputation, transformation and scaling","volume":"12","author":"Engel","year":"2016","journal-title":"Metabolomics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1021\/acs.jproteome.5b00354","article-title":"Analysis of the human adult urinary metabolome variations with age, body mass index, and gender by implementing a comprehensive workflow for univariate and OPLS statistical analyses","volume":"14","author":"Roux","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: Integrating viruses and cellular organisms","volume":"49","author":"Kanehisa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"el Bouhaddani, S., Uh, H.-W., Jonges, G., Hayward, C., and Houwing-Duistermaat, J.J. (2018). Integrating omics datasets with the OmicsPLS package. BMC Bioinform., 19.","DOI":"10.1186\/s12859-018-2371-3"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/cem.695","article-title":"Orthogonal projections to latent structures (O-PLS)","volume":"16","author":"Trygg","year":"2002","journal-title":"J. Chemom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v061.i06","article-title":"NbClust: An R Package for Determining the Relevant Number of Clusters in a Data Set","volume":"61","author":"Charrad","year":"2014","journal-title":"J. Stat. Softw."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s002530000396","article-title":"Fruiting body production in basidiomycetes","volume":"54","author":"Liu","year":"2000","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kang, Z., Yuan, X., Zhang, C., Wang, Y., Li, L., and Zheng, Y. (2025). Genomic and multi-omics analysis of Phlebopus portentosus secondary metabolism under different cultivation conditions. J. Fungi, 11.","DOI":"10.3390\/jof11040323"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/16\/1343\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:40:28Z","timestamp":1786326028000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/16\/1343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,8]]},"references-count":38,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["biology15161343"],"URL":"https:\/\/doi.org\/10.3390\/biology15161343","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,8]]}}}