Loïc Mangnier, Antoine Bodein, Margaux Mariaz, Alban Mathieu, Marie-Pier Scott-Boyer, Neerja Vashist, Matthew S Bramble, Arnaud Droit
{"title":"A systematic benchmark of integrative strategies for microbiome-metabolome data.","authors":"Loïc Mangnier, Antoine Bodein, Margaux Mariaz, Alban Mathieu, Marie-Pier Scott-Boyer, Neerja Vashist, Matthew S Bramble, Arnaud Droit","doi":"10.1038/s42003-025-08515-9","DOIUrl":"https://doi.org/10.1038/s42003-025-08515-9","url":null,"abstract":"<p><p>The rapid advancement of high-throughput sequencing technologies has enabled the integration of various omic layers into computational frameworks. Among these, metagenomics and metabolomics are increasingly studied for their roles in complex diseases. However, no standard currently exists for jointly integrating microbiome and metabolome datasets within statistical models. We benchmarked nineteen integrative methods to disentangle the relationships between microorganisms and metabolites. These methods address key research goals, including global associations, data summarization, individual associations, and feature selection. Through realistic simulations, we identified the best-performing methods and validated them on real gut microbiome datasets, revealing complementary biological processes across the two omic layers. Practical guidelines are provided for specific scientific questions and data types. This work establishes a foundation for research standards in metagenomics-metabolomics integration and supports future methodological developments, while also providing guidance for designing optimal analytical strategies tailored to specific integration questions.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1100"},"PeriodicalIF":5.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyeonseob Lim, Soyeong Jun, Taehoon Kim, Ji Hyun Lee, Duhee Bang
{"title":"Correcting errors in PCR-derived libraries for rare allele detection by reconstructing parental and daughter strand information.","authors":"Hyeonseob Lim, Soyeong Jun, Taehoon Kim, Ji Hyun Lee, Duhee Bang","doi":"10.1038/s42003-025-08537-3","DOIUrl":"https://doi.org/10.1038/s42003-025-08537-3","url":null,"abstract":"<p><p>Molecular barcoding methods enable high-sensitivity detection of circulating tumor DNA that is rarely present in liquid biopsy samples. Many methods involve ligation of molecular barcodes to DNA prior to hybridization capture, enabling recovery of starting molecules. Development of polymerase chain reaction (PCR)-based methods could facilitate more cost- and labor- effective detection; however, tracking molecular identity can be difficult, as new barcodes overwrite old barcodes in each cycle. Here, we present a sensitive genotyping method based on a peer-to-peer network-derived identifier for error reduction in amplicon sequencing (SPIDER-seq) and enable molecular identity tracking with PCR-derived libraries using overwritten barcodes. SPIDER-seq detected mutations at frequences as low as 0.125% after only two consecutive general PCR cycles and systematically analyzed the error pattern in the peer-to-peer network. Our method could facilitate the rapid detection of mutations associated with various cancers.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1098"},"PeriodicalIF":5.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lena Gonner, Eric A Cassens, Simone König, Ivan A Berg
{"title":"Pseudomonadal itaconate degradation gene cluster encodes enzymes for methylsuccinate utilization.","authors":"Lena Gonner, Eric A Cassens, Simone König, Ivan A Berg","doi":"10.1038/s42003-025-08538-2","DOIUrl":"https://doi.org/10.1038/s42003-025-08538-2","url":null,"abstract":"<p><p>Branched-chain C<sub>5</sub>-dicarboxylic acids (e.g., citramalate, mesaconate or methylsuccinate) and their CoA-esters are important intermediates in bacterial metabolism, while itaconate is an antimicrobial agent, a potent immunomodulator and a growth substrate for many bacteria. The itaconate degradation pathway consists of three reactions catalyzed by itaconate CoA transferase, itaconyl-CoA hydratase and (S)-citramalyl-CoA lyase encoded in a cluster, which in saprophytic bacteria contains two additional genes for a putative acyl-CoA dehydrogenase and a protein of the MmgE/PrpD family. Here, we heterologously produced the corresponding proteins from Cupriavidus necator and Pseudomonas aeruginosa and showed that they catalyze the (RS)-methylsuccinyl-C4-CoA dehydrogenase and an (S)-(R)-methylsuccinate isomerase reaction, respectively. Together with itaconate CoA transferase, which is highly active with (R)-methylsuccinate but has low activity with (S)-methylsuccinate, these enzymes allow the utilization of both stereoisomers of methylsuccinate. Our bioinformatic analysis revealed that 1.6% of the sequenced prokaryotes (mainly Betaproteobacteria) possess an identified methylsuccinate isomerase. Analysis of the conserved amino acids of methylsuccinate isomerase and other MmgE/PrpD proteins suggests that they share a common catalytic mechanism via the formation of an enolate intermediate. The presence of specific methylsuccinate utilization genes in the itaconate degradation cluster, which is widespread in saprophytic bacteria, suggests the importance of methylsuccinate in the environment.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1099"},"PeriodicalIF":5.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Agxt2l-mediated glycerophospholipid metabolism in trophocytes explains Apis mellifera queen's higher oviposition over A. cerana.","authors":"Luxia Pan, Zilong Wang, Shiqing Zhong, Tianyu Xu, Weixuan Chen, Fuping Cheng, Zhijiang Zeng","doi":"10.1038/s42003-025-08526-6","DOIUrl":"https://doi.org/10.1038/s42003-025-08526-6","url":null,"abstract":"<p><p>Apis mellifera and Apis cerana are two important honey bee species widely kept and studied. But their queens differ greatly in egg-laying capacity. To determine the mechanisms of this difference, we compare gene expression, chromatin accessibility and spatial localization of differential genes in the ovaries of the two species in virgin queens and laying queens using ATAC-seq, RNA-Seq, homologous gene alignment and spatial transcriptome. The results reconfirm that the egg-laying capability of A. mellifera queens is significantly higher than that of A. cerana queens. The chromatin accessibility and nutrient cells ratio of A. mellifera queens are higher than those of A. cerana queens. Further investigations reveal that agxt2l (LOC408817) is significantly over-expressed in the ovaries of A. mellifera queens compared to A. cerana queens and is crucial for ovary development. Moreover, agxt2l can increase the phospholipid content in ovarian nutrient cells through the glycerophospholipid metabolism pathway to promote embryo formation and is regulated by brc-z1 (LOC552255). These findings suggest that the brc-z1-agxt2l signal pathway causes increased egg-laying in the queens of A. mellifera compared to the queens of A. cerana by accelerating lipid synthesis due to heightened glycerophospholipid metabolism.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1091"},"PeriodicalIF":5.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Variation and disparity within the inner ear and trigeminus of the tenrecomorpha.","authors":"R Benjamin Sulser, Ross D E MacPhee","doi":"10.1038/s42003-025-08489-8","DOIUrl":"https://doi.org/10.1038/s42003-025-08489-8","url":null,"abstract":"<p><p>Evolutionary theory predicts that sensory systems should adaptively respond to environmental selection. Different ecological niches should, in theory, then correlate with changes in sensory anatomy in lineages that have undergone extensive radiation. The afrotherian clade Tenrecomorpha, comprising of African potamogalines and Malagasy tenrecines, is of particular interest because of its variety: the clade reportedly includes fossorial, arboreal, semiaquatic, and even echolocating taxa. To investigate their sensory ecology, we provide geometric morphometric analyses of inner ear endocasts of 24 tenrec species. We expand this dataset with 9 iodine-stained specimens to study trigeminal organization. Although tenrecomorphs display cross-taxon differences in sensory structures, our analyses distinguish signals of conflicting strength and direction within the tenrec ear, with no single factor that might explain a substantial portion of observed variation when accounting for phylogeny. This contrasts with prior studies of the tenrec cranial endocast, where sensory ecotype and habitat are strongly associated with shape. Iodine-enhanced scans of the trigeminal nerve align with this, and other studies based on bony anatomy. The disparate patterns of shape evolution in Tenrecomorpha and the contrasts exhibited by the inner ear and trigeminal nerve provide a nuanced portrait of neurosensory adaptation, differing from expectations set by other mammalian groups.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1090"},"PeriodicalIF":5.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kimberly Kajihara, Donghong Yan, Gretchen L Seim, Hannah Little-Hooy, Jing Kang, Cynthia Chen, Marco De Simone, Tim Delemarre, Spyros Darmanis, Haridha Shivram, Rebecca N Bauer, Carrie M Rosenberger, Sharookh B Kapadia, Min Xu, Miguel Reyes
{"title":"Systemic cytokines drive conserved severity-associated myeloid responses across bacterial and viral infections.","authors":"Kimberly Kajihara, Donghong Yan, Gretchen L Seim, Hannah Little-Hooy, Jing Kang, Cynthia Chen, Marco De Simone, Tim Delemarre, Spyros Darmanis, Haridha Shivram, Rebecca N Bauer, Carrie M Rosenberger, Sharookh B Kapadia, Min Xu, Miguel Reyes","doi":"10.1038/s42003-025-08407-y","DOIUrl":"https://doi.org/10.1038/s42003-025-08407-y","url":null,"abstract":"<p><p>Both bacterial and viral infections can trigger an overwhelming host response, leading to immunopathology and organ dysfunction. Multiple studies have reported dysregulated myeloid cell states in patients with bacterial sepsis or severe SARS-CoV-2 infection. However, their relevance to viral infections other than COVID-19, the factors driving their induction, and their role in tissue injury remain poorly understood. Here, we performed a multi-cohort analysis of single cell and bulk transcriptomic data from 1845 patients across 25 studies. Our meta-analysis revealed a conserved severity-associated gene signature pointing to emergency myelopoiesis (EM) and increased IL1R2 expression in monocytes and neutrophils from patients with bacterial sepsis, COVID-19, and influenza. Analysis of tocilizumab-treated COVID-19 patients showed that IL-6 signaling blockade partially reduces this signature and results in a compensatory increase in G-CSF. To validate the role of these cytokines in vivo, we used a mouse model of influenza infection that recapitulates severity-associated increases in IL1R2+ monocytes and IL1R2<sup>hi</sup> neutrophils, and demonstrate that combined IL-6 and G-CSF blockade inhibits their production. Our study demonstrates the cooperative role of G-CSF and IL-6 in driving the production of severity-associated IL1R2+ myeloid cells and highlights the link between myeloid dysregulation and tissue injury during severe infection.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1096"},"PeriodicalIF":5.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The microtubule-severing enzyme spastin regulates spindle dynamics to promote chromosome segregation in Trypanosoma brucei.","authors":"Thiago Souza Onofre, Qing Zhou, Ziyin Li","doi":"10.1038/s42003-025-08505-x","DOIUrl":"https://doi.org/10.1038/s42003-025-08505-x","url":null,"abstract":"<p><p>Microtubule-severing enzymes play essential roles in diverse cellular processes, including mitosis and cytokinesis, by modulating microtubule dynamics. In the early branching Trypanosoma brucei, microtubule-severing enzymes are involved in cytokinesis and flagellum length control, but none of them have been found to regulate mitosis. Here we report the characterization of the microtubule-severing enzyme spastin in the procyclic form of T. brucei. We demonstrate that spastin severs microtubule in vitro and overexpression of spastin disrupts spindle microtubules in vivo in trypanosomes, leading to defective chromosome segregation. Knockdown of spastin impairs spindle integrity and disrupts chromosome alignment and segregation. We further show that the function of spastin requires the catalytic AAA-ATPase domain, the microtubule-binding domain, and the microtubule interacting and trafficking domain, and that the association of spastin with spindle depends on the microtubule-binding domain. Together, these results uncover important roles for spastin in chromosome segregation by regulating spindle dynamics in T. brucei.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1095"},"PeriodicalIF":5.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhen Xie, Qinghu Yang, Fei Lan, Wei Kong, Shuxuan Zhao, Jinyi Sun, Yan Yan, Zhenzhen Quan, Zhantao Bai, Hong Qing, Jian Mao, Junjun Ni
{"title":"Cathepsin B deficiency disrupts cortical development via PEG3, leading to depression-like behavior.","authors":"Zhen Xie, Qinghu Yang, Fei Lan, Wei Kong, Shuxuan Zhao, Jinyi Sun, Yan Yan, Zhenzhen Quan, Zhantao Bai, Hong Qing, Jian Mao, Junjun Ni","doi":"10.1038/s42003-025-08508-8","DOIUrl":"https://doi.org/10.1038/s42003-025-08508-8","url":null,"abstract":"<p><p>Cathepsin B (CatB), a protease in endosomal and lysosomal compartments, plays a key role in neuronal protein processing and degradation, but its function in brain development remains unclear. In this study, we found that CatB is highly expressed in the cortex of E12.5-E16.5 mice. Morphological analysis revealed significant defects in cortical development in CatB knockout (KO) mice, particularly in layer 6. In vitro experiments showed that CatB deficiency notably impaired neuronal migration and development. Behaviorally, CatB KO mice displayed prominent depressive-like behaviors, and electrophysiological recordings demonstrated significantly reduced neuronal activity in layer 6 of the medial prefrontal cortex. Mechanistically, proteomics analysis revealed that CatB KO affected neuronal migration and axonal growth, and decreased the expression of key transcription factors involved in neuronal development, particularly PEG3. Deficiency of PEG3 also significantly impaired neuronal migration and development. Our findings uncover a role for CatB in cortical development and suggest a mechanism linking CatB deficiency with depression and developmental defects through the destabilization of PEG3.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1097"},"PeriodicalIF":5.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuliia Fatieieva, Rozalina Galimullina, Sergey Isaev, Alexander Klimovich, Laurence A Lemaire, Igor Adameyko
{"title":"Melanocytes and photosensory organs share a common ancestry that illuminates the origins of the neural crest.","authors":"Yuliia Fatieieva, Rozalina Galimullina, Sergey Isaev, Alexander Klimovich, Laurence A Lemaire, Igor Adameyko","doi":"10.1038/s42003-025-08502-0","DOIUrl":"https://doi.org/10.1038/s42003-025-08502-0","url":null,"abstract":"<p><p>In vertebrates, two major cell types produce extensive pigmentation: neuroepithelium-derived retinal pigment epithelium (RPE) of the eye and neural crest-derived melanocytes. Both produce melanin, express opsins, and exhibit photosensory functions. However, the evolutionary relationship between these cells - whether pigmentation was coopted or they share a common ancestry - remains unclear. We explore these scenarios including the hypothesis of a shared origin from an ancestral pigmented photosensory structure. For this, we harness single cell transcriptomics, chromatin accessibility and spatial transcriptomics data, to connect the transcriptional programs in melanocytes, pinealocytes and RPE with that of the pigmented cells in the sensory vesicle of the tunicate Ciona. The results reveal common regulatory gene expression modules spanning beyond pigment production, including photoreception, metabolism and biosynthesis. This evidence does not favor a model where pigmentation was coopted into one of these cell types, and rather supports the homology of melanocytes and RPE. Further, phylotranscriptomics approach expose recently-evolved melanocyte-specific and RPE-specific functions, which diversified after these types split from the ancestral cell type. Overall, our results support that melanocytes and RPE evolved from ancestral pigmented photosensory structures in chordates, initiating the origin of the neural crest - a major evolutionary driver of the vertebrate lineage.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1092"},"PeriodicalIF":5.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Richard J Knecht, Christian R A McCall, Cheng-Chia Tsai, Richard A Rabideau Childers, Nanfang Yu
{"title":"Palaeocampa anthrax, an armored freshwater lobopodian with chemical defenses from the Carboniferous.","authors":"Richard J Knecht, Christian R A McCall, Cheng-Chia Tsai, Richard A Rabideau Childers, Nanfang Yu","doi":"10.1038/s42003-025-08483-0","DOIUrl":"https://doi.org/10.1038/s42003-025-08483-0","url":null,"abstract":"<p><p>Lobopodians are an evolutionary grade of panarthropods characterized by their vermiform bodies and paired, unjointed lobopodous legs. A paraphyletic group, their study is of particular significance in understanding the evolution of extant panarthropods. Found exclusively in marine deposits from the Paleozoic, the great majority of species come from Cambrian Konservat-Lagerstätten, with only a few representatives known from the Ordovician, Silurian, and Carboniferous. Here we redescribe Palaeocampa anthrax from the Carboniferous Mazon Creek (USA) and Montceau-les-Mines (France) Lagerstätten as a lobopodian. First published in 1865, nearly fifty years before the discovery of the Burgess Shale, Palaeocampa is historically the first discovered lobopod, and its presence at the slightly younger Montceau-les-Mines (Gzhelian), makes this the youngest known fossil 'xenusiid' lobopodian species. We present the case that Palaeocampa most likely inhabited a freshwater environment, contesting the view that Paleozoic lobopodians were exclusively marine. Palaeocampa bears biomineralized dorso-lateral and lateral sclerite sets with a unique architecture unseen in other lobopodian sclerites, which may have been capable of secreting defensive chemicals at their tips. Palaeocampa anthrax represents a major evolutionary step in lobopodians, both in environmental adaptations and in defensive abilities.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1080"},"PeriodicalIF":5.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}