BMC BiologyPub Date : 2026-05-26DOI: 10.1186/s12915-026-02639-y
Romana Vargová, Vladislava Majnušová, Marek Eliáš
{"title":"Comprehensive analysis of small GTPases in Microsporidia reveals new extremes in eukaryotic cell biology.","authors":"Romana Vargová, Vladislava Majnušová, Marek Eliáš","doi":"10.1186/s12915-026-02639-y","DOIUrl":"10.1186/s12915-026-02639-y","url":null,"abstract":"<p><strong>Background: </strong>Microsporidia are a fungi-related rapidly evolving lineage of obligate intracellular parasites with poorly known cell biology. Cellular processes in eukaryotes heavily rely on a group of proteins known as the Ras GTPase superfamily, so a comprehensive analysis of these proteins in Microsporidia is expected to provide fundamental insights into the microsporidian cell biology. Adopting a complex bioinformatic approach to cope with the high divergence of microsporidian genes, we reconstructed the evolutionary history of the Ras superfamily of GTPases in Microsporidia and their closest relatives.</p><p><strong>Results: </strong>Our results demonstrate that gene loss along the whole microsporidian phylogeny has been a vastly dominating factor shaping the Ras superfamily gene complements in extant Microsporidia. This trend has most massively affected Hepatospora eriocheir with a mere 12 Ras superfamily genes, the smallest number recorded so far for an autonomously reproducing eukaryote. Also notable is the loss of the virtually ubiquitous Rab GTPase Rab5 and its dedicated regulators in two different microsporidian lineages, or the Rho family GTPases of most Microsporidia having lost C-terminal prenylation. Most unexpectedly, two different microsporidian species lack detectable orthologs of the beta subunit of the signal recognition particle (SRP) receptor, a loss unknown from any other eukaryote. Strikingly, the loss of SRβ is apparently compensated for by the SRP receptor alpha subunit of these species uniquely possessing a predicted transmembrane domain, potentially anchoring the protein in the ER membrane.</p><p><strong>Conclusions: </strong>Our findings thus define new extremes in the impact of reductive evolution on core processes of the eukaryotic cell.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013788","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 : 2026-05-23DOI: 10.1186/s12915-026-02621-8
Mireia Mestre, Alicia Prior, Camila Marín-Arias, Daniel R Rodríguez-Solís, Rafael Laso-Pérez, Emilio Alarcón, Valeska Vásquez-Lepio, Humberto E González, Ramiro Logares, Jesse McNichol, Jed Fuhrman, Camila Fernandez, Mark J Hopwood, Juan Höfer
{"title":"Microbial fingerprinting of marine water masses in an Antarctic and hydrographically complex area.","authors":"Mireia Mestre, Alicia Prior, Camila Marín-Arias, Daniel R Rodríguez-Solís, Rafael Laso-Pérez, Emilio Alarcón, Valeska Vásquez-Lepio, Humberto E González, Ramiro Logares, Jesse McNichol, Jed Fuhrman, Camila Fernandez, Mark J Hopwood, Juan Höfer","doi":"10.1186/s12915-026-02621-8","DOIUrl":"10.1186/s12915-026-02621-8","url":null,"abstract":"<p><strong>Background: </strong>Microorganisms are ubiquitous in marine ecosystems, yet the influence of water masses on their distribution remains underexplored, particularly in extreme environments such as Antarctica. This study examines microbial communities in the Gerlache-Bismarck Strait, a region with complex hydrography. We analyzed both prokaryotic and eukaryotic diversity alongside multiple oceanographic and biogeochemical variables. Water samples were collected from 1 to 400 m depth across three size fractions: pico- (0.2-3 µm), nano- (3-20 µm), and microparticles (20-200 µm).</p><p><strong>Results: </strong>Our results indicate that water mass composition is a primary driver of microbial community assembly. Surface water masses included Antarctic Surface Waters (AASW), Glacially Modified Waters (GMW), and Transitional Zonal Waters influenced by the Bellingshausen Sea (TBW), whereas intermediate and deep layers comprised Transitional Zonal Waters influenced by the Weddell Sea (TWW) and Circumpolar Deep Waters (CDW). This study provides direct evidence of close links between microorganisms and water masses, showing that marine microbial communities are shaped not only by local conditions but also by water masses circulation. We use the concept of \"microbial fingerprinting of water masses\" establishing microbial communities as ecological indicators and providing framework applicable to other marine systems.</p><p><strong>Conclusions: </strong>Microbial fingerprints provided insight into the role of the water masses in biogeochemistry and food webs of this area (e.g., the ammonia-oxidizing archaea Nitrosopumilaceae in the CDW, and the phototroph Chrysochromulina simplex in the GMW). This information is useful to predict how future changes in ocean circulation and microbial distribution may alter ecosystem services in this critical region.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004831","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 : 2026-05-22DOI: 10.1186/s12915-026-02641-4
Gabor S Szilagyi, Attila Gulyas, Zsolt Vassy, Peter Csermely, Bank G Fenyves
{"title":"Signed motif analysis of the Caenorhabditis elegans neuronal network reveals positive feedforward and negative feedback loops.","authors":"Gabor S Szilagyi, Attila Gulyas, Zsolt Vassy, Peter Csermely, Bank G Fenyves","doi":"10.1186/s12915-026-02641-4","DOIUrl":"10.1186/s12915-026-02641-4","url":null,"abstract":"<p><strong>Background: </strong>Nervous systems are complex biological networks with largely unknown structural and functional characteristics. Motif analysis is a robust tool that can reveal the unique aspects of connectivity in a complex network. An ideal candidate for motif analysis is the connectome of the nematode Caenorhabditis elegans, which is the first fully reconstructed nervous system.</p><p><strong>Results: </strong>We performed, for the first time, edge polarity-based signed motif analysis on the C. elegans connectome using recent data on the connection signs of this network and a novel structure-preserving randomization method. We identified 56 significantly over- and 1 underrepresented three-node signed motifs and revealed that certain motifs (e.g., positive feedforward, negative feedback, disinhibitory feedback, and incoherent feedforward loops) are overabundant in the C. elegans connectome. We further distinguished nodes by their corresponding neuron modalities (e.g., sensory vs. motor neurons), and found that each significant feedforward and feedback loop has a characteristic neuronal layout.</p><p><strong>Conclusions: </strong>Our findings demonstrate the importance and potential of signed motif analysis in understanding biological networks. The motif enumeration tool and definition system we developed can be used to analyze signed motifs in other complex networks.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986843","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 : 2026-05-21DOI: 10.1186/s12915-026-02634-3
Yang Li, Yadong Liu, Xian Chen, Weize Kong, Yadong Wang, Tao Jiang
{"title":"cyberDMR: accurate and robust identification of differentially methylated regions from WGS-derived methylomes.","authors":"Yang Li, Yadong Liu, Xian Chen, Weize Kong, Yadong Wang, Tao Jiang","doi":"10.1186/s12915-026-02634-3","DOIUrl":"10.1186/s12915-026-02634-3","url":null,"abstract":"<p><strong>Background: </strong>Differentially methylated regions (DMRs) are essential regulatory features for characterizing epigenetic variation, understanding population-level differences, and interpreting haplotype-specific methylation patterns. However, existing DMR detection methods often show unstable performance under biologically challenging scenarios such as sparse CpG regions, low sequencing depth, small sample sizes, extreme region lengths, and subtle methylation differences. These limitations highlight the need for a more robust and versatile approach capable of achieving accurate and consistent DMR detection across diverse genomic contexts. To address these challenges, we developed cyberDMR, a robust and noise-resilient DMR detection framework that integrates coverage-adaptive smoothing, seed-growing clustering, and weighted beta regression to achieve stable performance under whole-genome sequencing (WGS) and varying sequencing conditions.</p><p><strong>Results: </strong>cyberDMR consistently achieved the highest F1-scores on real WGBS prostate cancer datasets, outperforming other strong-performing methods by 2-18%. This advantage was further supported by extensive simulations spanning diverse genomic and experimental scenarios, in which cyberDMR maintained stable and leading performance, achieving a mean F1-score of 99.7% (± 0.3%) and consistently outperforming competing methods across diverse simulated settings. When applied to long-read methylation datasets, cyberDMR enabled the identification of 107 biologically meaningful methylation regions, including 15 gene-associated regions influenced by cis-acting methylation quantitative trait loci (meQTLs) and 2 corresponding putative novel imprinting candidates, ZNF714 and NINJ2.</p><p><strong>Conclusions: </strong>cyberDMR provides a robust and accurate framework for genome-wide DMR detection, capturing consistent inter-group methylation differences while preserving intra-group consistency across diverse sequencing conditions.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986850","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 : 2026-05-21DOI: 10.1186/s12915-026-02643-2
Mariana Roza de Abreu, Emilie Cardona, Camille Lagarde, Leo Milhade, Goro Yoshizaki, Violette Thermes, Julien Bobe
{"title":"Circulating microRNAs reveal egg-brain crosstalk and a brain-predominant microRNA linked to the onset of the next reproductive cycle in iteroparous salmonids.","authors":"Mariana Roza de Abreu, Emilie Cardona, Camille Lagarde, Leo Milhade, Goro Yoshizaki, Violette Thermes, Julien Bobe","doi":"10.1186/s12915-026-02643-2","DOIUrl":"10.1186/s12915-026-02643-2","url":null,"abstract":"<p><strong>Background: </strong>Mechanisms regulating the transition between two consecutive reproductive cycles are complex and remain poorly understood, mostly because they involve a dialog between the ovary and the central nervous system that is difficult to disentangle.</p><p><strong>Results: </strong>In rainbow trout (Oncorhynchus mykiss), an iteroparous species spawning every year, removal of the eggs from the body cavity was used as a switch to trigger the onset of the next reproductive cycle. Changes in circulating miRNAs (c-miRNAs) levels in blood plasma and ovarian fluid were then monitored over time. Upon removal of the eggs from the body cavity, we observed the dramatic downregulation of the blood plasma levels of a single c-miRNA (miR-139-5p) that is predominantly expressed in the brain. In contrast, very distinct c-miRNAs profiles were observed in blood plasma when eggs are retained in the body cavity. Among plasma c-miRNAs showing dynamic changes with egg retention, miR-135c is strongly expressed in the brain and pituitary, while miR-457a is predominant in the post-ovulatory ovary. In addition, egg retention in the body cavity triggers a dramatic drop in ovarian fluid levels of miR-202-5p, a miRNA known to regulate egg production in fish.</p><p><strong>Conclusions: </strong>Our observations reveal that the transition between two successive reproductive cycles involves a crosstalk between the eggs and the central system and that a single miRNA, miR-139, predominantly expressed in the brain, is associated with the onset of the next reproductive cycle. We identified possible miR-139-5p functional targets in rainbow trout and other iteroparous species that have been lost in semelparous salmonids. Our results offer new research perspectives to better understand the mechanisms triggering the next reproductive cycle in iteroparous fish species, including post-transcriptional regulations by miR-139 in the brain.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986865","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":"Isolation and characterization of LH5, a novel rodent Embecovirus from Rattus tanezumi with respiratory tropism in a mouse model.","authors":"Qian Li, Keyao Xia, Yutong Hou, Xiang Le, Yayu Fan, Yushan Kui, Lulu Deng, Binghui Wang, Xueshan Xia","doi":"10.1186/s12915-026-02638-z","DOIUrl":"10.1186/s12915-026-02638-z","url":null,"abstract":"<p><strong>Background: </strong>Coronaviruses (CoVs) have contributed substantially to recent global public health crises (e.g., SARS, SARS-CoV-2, and MERS-CoV). Wild animals are the primary natural reservoirs of CoVs prior to human transmission.</p><p><strong>Results: </strong>In this study, we report the isolation and characterization of a novel β-CoV strain, designated Murine-CoV-LH5, from Rattus tanezumi in Dehong Prefecture, Yunnan Province. This represents, to our knowledge, the first reported isolation of a coronavirus from this specific rodent species. Genomic analysis confirmed its classification within the subgenus Embecovirus. Notably, the genome encodes a furin cleavage site in the spike protein, a feature uncommon among known rodent Embecovirus, whose functional significance warrants further investigation. Molecular docking analysis predicted strong binding affinities between the LH5 spike protein and human host factors TMPRSS2 and ACE2, suggesting a potential interaction that requires experimental validation. The virus was isolated using intracerebral inoculation in neonatal mice. In this mouse model, immunohistochemistry and indirect immunofluorescence revealed viral tropism for bronchial and alveolar epithelial cells in the lungs, as well as cortical neurons in the brain. Furthermore, the establishment of a mouse-adapted LH5 strain provides a valuable in vivo model system for studying Embecovirus pathogenesis and for antiviral drug screening, particularly in research settings where handling high-containment pathogens is constrained.</p><p><strong>Conclusions: </strong>This study provides the initial characterization of LH5, including its genomic features and tropism in a laboratory mouse model. These findings contribute to the understanding of rodent CoV diversity and evolution, demonstrate the utility of LH5 as a tractable research model, and highlight the importance of continued surveillance of wildlife CoVs for assessing zoonotic potential.</p><p><strong>Importance: </strong>Our study contributes to the understanding of CoV diversity in wildlife by reporting the isolation and initial characterization of a novel β-CoV (LH5) from Rattus tanezumi. While rodents are known reservoirs for various CoVs, the successful isolation of a replicative strain from this specific host provides a crucial in vivo model for research. This is particularly significant as LH5 demonstrates clear pulmonary tropism in a standard laboratory mouse model, offering a tractable and accessible system to study Embecovirus pathogenesis and host interactions in the respiratory tract, which can be leveraged for antiviral screening. Furthermore, the identification of genomic features in LH5, such as a furin cleavage site uncommon in rodent Embecovirus and predicted human receptor-binding potential, highlights the need for experimental studies to assess its zoonotic risk. Our findings emphasize that continuous surveillance of CoVs in rodent populations is essential","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986857","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 : 2026-05-20DOI: 10.1186/s12915-026-02640-5
Elena Bellavere, Francesc Mesquita-Joanes, Donato Romano, Giampaolo Rossetti
{"title":"Evidence of visual learning and wavelength differential responses in three podocopids (Crustacea: Ostracoda).","authors":"Elena Bellavere, Francesc Mesquita-Joanes, Donato Romano, Giampaolo Rossetti","doi":"10.1186/s12915-026-02640-5","DOIUrl":"10.1186/s12915-026-02640-5","url":null,"abstract":"<p><strong>Background: </strong>Ostracods are small bivalved crustaceans that inhabit a wide range of aquatic environments, from fully marine to brackish and freshwater systems. All non-marine species belong to the order Podocopida. The sensory biology and behavioral capacities of ostracods remain poorly understood, even though these traits play pivotal roles in habitat exploration, food searching, mate recognition, and predator avoidance. In particular, studies addressing vision and learning ability are still scarce. Although visual structures in ostracods are often reduced or simplified, they exhibit considerable variation across taxa. In this study, we investigated the photoreceptive capabilities of three podocopid species, Vizcainocypria viator, Loxoconcha elliptica, and Xestoleberis nitida, representing different families. Using miniaturized, three-chamber lab-on-a-chip arenas, we examined both innate and experience-dependent light-guided behaviors, testing whether differential wavelength sensitivity and learned associations are present, if these traits are species-specific, and which locomotory responses are associated with them.</p><p><strong>Results: </strong>Our results provide evidence for a simple form of long-term associative memory in ostracods, together with species-specific responses to conditioning type, light wavelength, and possibly light intensity. These responses were not restricted to spatial preferences among arena chambers, but also affected locomotory behavior.</p><p><strong>Conclusions: </strong>These findings highlight ostracods as valuable model organisms for studying fundamental biological processes such as sensory integration, behavioral plasticity, and learning. More broadly, this research advances our understanding of sensory evolution in crustaceans and sheds new light on the behavioral complexity of small aquatic invertebrates.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980658","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 : 2026-05-19DOI: 10.1186/s12915-026-02632-5
Marcela Uliano-Silva, Helena Beatriz da Conceição, Rafael L V Mercuri, Sylke Winkler, Gabriela D A Guardia, Eugene Myers, Shane McCarthy, Alan Tracey, Alexander Suh, Mark Blaxter, Pedro A F Galante, Camila J Mazzoni
{"title":"Elevated retrocopy burden and sloth-specific expansions illuminate mammalian genome evolution.","authors":"Marcela Uliano-Silva, Helena Beatriz da Conceição, Rafael L V Mercuri, Sylke Winkler, Gabriela D A Guardia, Eugene Myers, Shane McCarthy, Alan Tracey, Alexander Suh, Mark Blaxter, Pedro A F Galante, Camila J Mazzoni","doi":"10.1186/s12915-026-02632-5","DOIUrl":"10.1186/s12915-026-02632-5","url":null,"abstract":"<p><strong>Background: </strong>Xenarthrans, comprising sloths, anteaters, and armadillos, represent one of the most morphologically and physiologically specialized mammalian clades, yet the genomic basis of their adaptations remains poorly understood. Here, we present chromosome-level genomes for the two-toed sloth (Choloepus didactylus) and the southern anteater (Tamandua tetradactyla) and investigate how retrotransposon-mediated gene duplications (retrocopies) have shaped genome evolution in these and other species in Xenarthra.</p><p><strong>Results: </strong>Comparative analyses revealed that the xenarthran genomes analyzed here harbour the highest number of retrocopies reported among mammals, with lineage-specific insertion dynamics. Anteater and armadillo genomes contain older LINE1 repertoires and species-specific older retrocopy insertions. In contrast, sloths retain both an abundance of young LINE1s and thousands of young retrocopies, alongside a large shared set that originated from an evolutionary burst of retroduplication in the branch leading to their last common ancestor (~ 30 Mya). In C. didactylus, 49% of retrocopies were found to be expressed in five tissues, compared with 27% in Dasypus novemcinctus in three tissues. Evolutionary analyses identified 38 retrocopies with strong hallmarks of domestication in C. didactylus. Many of these retrocopies derive from parental genes involved in mitochondrial and metabolic processes, suggesting a potential genomic contribution to the physiological specializations of sloths.</p><p><strong>Conclusions: </strong>Altogether, our findings identify retrotransposition as a major contributor to the genomic architecture of the xenarthrans presented here and highlight retrocopy origination as a mechanism for generating lineage-specific novelty and, possibly, distinctive biological specializations.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13251070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970555","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 : 2026-05-19DOI: 10.1186/s12915-026-02636-1
Shihu Jiao, Chunyan Ao, Quan Zou, Huan Yang
{"title":"KmalPred: a deep learning framework for lysine malonylation site prediction using protein language model representations.","authors":"Shihu Jiao, Chunyan Ao, Quan Zou, Huan Yang","doi":"10.1186/s12915-026-02636-1","DOIUrl":"10.1186/s12915-026-02636-1","url":null,"abstract":"<p><strong>Background: </strong>Lysine malonylation (Kmal) is a reversible post-translational modification involved in metabolic regulation and other essential biological processes across diverse species. Accurate identification of Kmal sites is important for understanding their biological functions, but experimental approaches such as mass spectrometry remain labor-intensive and time-consuming. Existing computational predictors often rely on local sequence windows and therefore may fail to fully capture long-range contextual information within proteins.</p><p><strong>Results: </strong>We present KmalPred, a deep learning framework for Kmal site prediction that combines ProtT5-derived residue representations with a bidirectional long short-term memory network. Unlike conventional segment-first pipelines, KmalPred first encodes the full-length protein sequence and then extracts lysine-centered windows from the resulting residue-level embeddings. This sequence-first design preserves global sequence context and avoids redundant computation over highly overlapping windows. On the independent test set, KmalPred achieved an accuracy of 0.78 and a Matthews correlation coefficient of 0.56, outperforming previously reported predictors evaluated on the same benchmark. Comparative analyses showed that the sequence-first strategy consistently performed better than the conventional segment-first strategy and that ProtT5 provided more informative representations than several other widely used protein language models. The framework also maintained stable performance under class-imbalance settings.</p><p><strong>Conclusions: </strong>KmalPred provides an effective and robust approach for large-scale screening of candidate Kmal sites. More broadly, the results highlight the value of full-sequence protein language model representations for residue-level post-translational modification prediction and suggest that this framework can be readily extended to other post-translational modification site prediction tasks.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970607","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":"Microbial enterotype is linked to episodic and working memories via brain function in the parietal and occipital cortices.","authors":"Yu Shi, Zhonghao Rao, Chenglong Liu, Min She, Yongqiang Yu, Jiajia Zhu","doi":"10.1186/s12915-026-02635-2","DOIUrl":"10.1186/s12915-026-02635-2","url":null,"abstract":"<p><strong>Background: </strong>Classification of human gut microbiome into distinct enterotypes based on gut microbial community composition has provided an attractive framework for population stratification. While empirical evidence indicates that microbial enterotype is related to brain function and memory, the neural processes underlying this interaction remain to be further characterized.</p><p><strong>Results: </strong>In 510 healthy young adults, we used 16S rDNA amplicon sequencing to perform enterotyping, acquired resting-state functional MRI data to calculate brain functional measures, and assessed both episodic and working memories. Inter-enterotype differences in brain functional measures were examined, followed by performance of correlation and mediation analyses to disentangle the potential associations between enterotype, brain function, and memory. We found significant differences in multiple brain functional measures in the parietal and occipital cortices across Bacteroides, Prevotella, and Ruminococcaceae enterotypes. Moreover, these differential brain functional measures were correlated with both episodic and working memories, and further mediated the relationship between enterotype and memory.</p><p><strong>Conclusions: </strong>Our findings not only establish brain function as the mediating factor between enterotype and memory, but also hold translational potential for informing novel treatment for cognitive dysfunction via targeting the microbiota-gut-brain axis.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970667","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}