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Human Cell Aging Transcriptome Atlas (HCATA): a single-cell atlas of age-associated transcriptomic alterations across human tissues. 人类细胞衰老转录组图谱(HCATA):人类组织中与年龄相关的转录组改变的单细胞图谱。
IF 5.1 1区 生物学
Communications Biology Pub Date : 2025-10-09 DOI: 10.1038/s42003-025-08845-8
Josh Bartz, Xiao Ma, Lei Zhang, Xiao Dong
{"title":"Human Cell Aging Transcriptome Atlas (HCATA): a single-cell atlas of age-associated transcriptomic alterations across human tissues.","authors":"Josh Bartz, Xiao Ma, Lei Zhang, Xiao Dong","doi":"10.1038/s42003-025-08845-8","DOIUrl":"https://doi.org/10.1038/s42003-025-08845-8","url":null,"abstract":"<p><p>Biological aging is associated with progressively more severe genetic and epigenetic alterations. While these changes are expected to affect the transcriptional profile of cells, the magnitude of that effect is unknown as the aging transcriptome is still poorly understood. Understanding the aging transcriptional landscape will give us greater insight into how cells are affected by and/or respond to the aging process. To facilitate the large-scale exploration of the aging transcriptome, we report the development of the Human Cell Aging Transcriptome Atlas (HCATA). HCATA, contains single-cell RNA-sequencing datasets from 76 publications totaling 92 million cells and 3,475 tissue-level samples across more than 50 tissue types with ages ranging from 0 to 103 years. HCATA includes a genome browser that allows users to interactively explore age-related differential expression, as well as functions to explore related pathways at the tissue and cell-type level. HCATA is publicly accessible at http://hcata-xiaodonglab.org:3304 .</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1450"},"PeriodicalIF":5.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257671","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}
引用次数: 0
Associations between fMRI signal amplitude, hemispheric asymmetry, and task performance. 功能磁共振成像信号振幅、半球不对称和任务表现之间的关系。
IF 5.1 1区 生物学
Communications Biology Pub Date : 2025-10-08 DOI: 10.1038/s42003-025-08843-w
Dardo Tomasi, Nora D Volkow
{"title":"Associations between fMRI signal amplitude, hemispheric asymmetry, and task performance.","authors":"Dardo Tomasi, Nora D Volkow","doi":"10.1038/s42003-025-08843-w","DOIUrl":"https://doi.org/10.1038/s42003-025-08843-w","url":null,"abstract":"<p><p>Interhemispheric asymmetry is a core feature of human brain organization, yet its functional relevance across cognitive tasks remains incompletely understood. Using data from 989 healthy adults, we examined patterns of functional asymmetry and their relationship to bilateral fMRI signal amplitude and task performance across seven tasks: motor, language, social cognition, relational processing, working memory, gambling, and emotion. An fMRI-derived asymmetry index was computed across 17 task epochs and mapped onto the cortical surface. Here we show that both fMRI signal amplitude and asymmetry were positively associated with task accuracy across multiple networks and tasks epochs. These associations were strongest in language, frontoparietal, and dorsal attention networks during high-demand tasks, such as story comprehension, relational processing, and working memory. Partial least squares regression revealed that amplitude was a more robust predictor of task accuracy than asymmetry. These findings suggest that greater neural activation drives stronger hemispheric differentiation and supports cognitive performance.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1439"},"PeriodicalIF":5.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250155","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}
引用次数: 0
Molecular mediators of cold adaptation in mammalian cells. 哺乳动物细胞冷适应的分子介质。
IF 5.1 1区 生物学
Communications Biology Pub Date : 2025-10-08 DOI: 10.1038/s42003-025-08838-7
Paulami Dey, Heera Lal, Pushpita Saha, Arvind Ramanathan
{"title":"Molecular mediators of cold adaptation in mammalian cells.","authors":"Paulami Dey, Heera Lal, Pushpita Saha, Arvind Ramanathan","doi":"10.1038/s42003-025-08838-7","DOIUrl":"https://doi.org/10.1038/s42003-025-08838-7","url":null,"abstract":"<p><p>Hypothermia is defined as a drop in temperature below the homeostatic range of cells and tissues. This elicits a response in mammalian cells geared towards cellular and metabolic adaptation. Hibernating mammals provide natural models of cold tolerance and adaptation. Mammalian cells across species share signaling mechanisms for adaptation to hypothermic stimuli. Key molecular mediators of hypothermic signaling, including: (i) cold-sensing ion channels such as TRPM8 and TRPA1, which link temperature changes to calcium signaling and thermoregulatory responses; (ii) β-adrenergic signaling and uncoupling protein 1 (UCP1)-mediated non-shivering thermogenesis in brown adipose tissue; (iii) cold-induced epigenetic modifications such as histone acetylation, DNA methylation, and enhancer activation that imprint transcriptional memory of cold exposure; and (iv) RNA-binding proteins CIRBP and RBM3, which are rapidly induced during mild-to-moderate hypothermia and confer neuroprotection, enhance differentiation, and modulate metabolism. Together, these findings outline a molecular framework by which mammalian cells sense, respond, and adapt to cold, with implications for neuroprotection, metabolic health, and therapeutic hypothermia.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1441"},"PeriodicalIF":5.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250115","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}
引用次数: 0
Caspofungin binding to iron compromises its antifungal efficacy against Candida albicans. caspofunin结合铁损害其抗真菌效果对白色念珠菌。
IF 5.1 1区 生物学
Communications Biology Pub Date : 2025-10-08 DOI: 10.1038/s42003-025-08834-x
Andreia Pedras, Cláudia Malta-Luís, Luís M P Lima, Dalila Mil-Homens, Catarina Amaral, Américo G Duarte, Wilson Antunes, Ana Gaspar-Cordeiro, Ricardo O Louro, Pedro Lamosa, Cláudio M Soares, Diana Lousa, Catarina Pimentel
{"title":"Caspofungin binding to iron compromises its antifungal efficacy against Candida albicans.","authors":"Andreia Pedras, Cláudia Malta-Luís, Luís M P Lima, Dalila Mil-Homens, Catarina Amaral, Américo G Duarte, Wilson Antunes, Ana Gaspar-Cordeiro, Ricardo O Louro, Pedro Lamosa, Cláudio M Soares, Diana Lousa, Catarina Pimentel","doi":"10.1038/s42003-025-08834-x","DOIUrl":"https://doi.org/10.1038/s42003-025-08834-x","url":null,"abstract":"<p><p>Echinocandins, which inhibit the synthesis of β-1,3-D-glucans, essential components of the fungal cell wall, are frontline drugs for invasive fungal infections (IFIs) caused by Candida spp. Recent in vitro studies have suggested that iron overload may reduce the efficacy of the echinocandin caspofungin against Candida albicans by altering its cell wall composition. Here, we show that iron loading conditions which do not interfere with the cell wall composition are still capable of recapitulating the caspofungin-resistant phenotype induced by iron. Spectroscopic analyses provided evidence that caspofungin binds to iron through its ethylenediamine moiety and two amide groups. Consistent with the in vitro activity of β-1,3-D-glucan synthase, the target of caspofungin, molecular dynamics simulations revealed that iron binding induces conformational changes in caspofungin, which may reduce its ability to inhibit the enzyme. Importantly, the in vivo antifungal efficacy of caspofungin was compromised in a Galleria mellonella model of IFI caused by C. albicans simulating a context of iron overload. This effect may extend beyond C. albicans infections, as the antagonism between iron and caspofungin was also observed in other medically important fungi causing IFIs.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1438"},"PeriodicalIF":5.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250158","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}
引用次数: 0
Carbon metabolism shapes FtsZ levels and cell division in the cyanobacterium Anabaena PCC 7120. 碳代谢影响蓝藻Anabaena PCC 7120的FtsZ水平和细胞分裂。
IF 5.1 1区 生物学
Communications Biology Pub Date : 2025-10-08 DOI: 10.1038/s42003-025-08849-4
Wen-Shuo Ran, Xiaoli Zeng, Cheng-Cai Zhang
{"title":"Carbon metabolism shapes FtsZ levels and cell division in the cyanobacterium Anabaena PCC 7120.","authors":"Wen-Shuo Ran, Xiaoli Zeng, Cheng-Cai Zhang","doi":"10.1038/s42003-025-08849-4","DOIUrl":"https://doi.org/10.1038/s42003-025-08849-4","url":null,"abstract":"<p><p>Cyanobacteria, as photoautotrophs, play key ecological roles and are widely used in synthetic biology research. While metabolism profoundly influences cellular processes like cell division, the regulatory mechanisms linking these activities remain poorly understood in cyanobacteria. Here, we perturb the tricarboxylic acid (TCA) pathway by introducing an extra CO2 fixation module in the model cyanobacterium Anabaena sp. PCC 7120. This modification alters the levels of the cell division protein FtsZ, impairing cell division under varying light conditions. We found that 2-oxoglutarate, an intermediate of the TCA pathway known as a metabolic signal, regulates ftsZ expression via the transcription factor NtcA. Furthermore, metabolic status modulates cell division in a NtcA-dependent manner, directly integrating metabolic control and cell division. Our findings uncover a coordination mechanism between metabolism and cell division in cyanobacteria, providing mechanistic insights for synthetic biology engineering and understanding of metabolic regulation.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1440"},"PeriodicalIF":5.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250182","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}
引用次数: 0
Evaluating the temporal order of motor and auditory systems in speech production using intracranial EEG. 颅内脑电图评价语音产生过程中运动和听觉系统的时间顺序。
IF 5.1 1区 生物学
Communications Biology Pub Date : 2025-10-08 DOI: 10.1038/s42003-025-08847-6
Siqi Li, Zihua Chen, Xikang Luo, Jing Wang, Pengfei Teng, Guoming Luan, Qian Wang, Xing Tian
{"title":"Evaluating the temporal order of motor and auditory systems in speech production using intracranial EEG.","authors":"Siqi Li, Zihua Chen, Xikang Luo, Jing Wang, Pengfei Teng, Guoming Luan, Qian Wang, Xing Tian","doi":"10.1038/s42003-025-08847-6","DOIUrl":"https://doi.org/10.1038/s42003-025-08847-6","url":null,"abstract":"<p><p>Theories propose that speech production can be approximated as a temporal reversal of speech perception. For example, phonological code is assumed to precede phonetic encoding in the motor system during speech production. However, empirical neural evidence directly testing the temporal order hypothesis remains scarce, mostly because of motor artifacts in non-invasive electrophysiology recordings and the requirements of both temporal and spatial precision. In this study, we investigated the neural dynamics of speech production using stereotactic electroencephalography (sEEG). In both onset latency analysis and representational similarity analysis (RSA), activation in the auditory region of the posterior superior temporal gyrus (pSTG) was observed before articulation, suggesting the availability of auditory phonological code before production. Surprisingly, the activation in the motor region of the inferior frontal gyrus (IFG) preceded that of pSTG, suggesting that the phonological code in the auditory domain may not necessarily be activated before the encoding in the motor domain during speech production.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1442"},"PeriodicalIF":5.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250185","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}
引用次数: 0
Optogenetic induction of subcellular Ca2+ events in megakaryocytes and platelets using a highly Ca2+-conductive channelrhodopsin. 利用高Ca2+导电通道视紫质在巨核细胞和血小板中诱导亚细胞Ca2+事件。
IF 5.1 1区 生物学
Communications Biology Pub Date : 2025-10-07 DOI: 10.1038/s42003-025-08924-w
Yujing Zhang, Jing Yu-Strzelczyk, Dmitri Sisario, Rebecca Holzapfel, Zoltan Nagy, Congfeng Xu, Chengxing Shen, Georg Nagel, Shiqiang Gao, Markus Bender
{"title":"Optogenetic induction of subcellular Ca<sup>2+</sup> events in megakaryocytes and platelets using a highly Ca<sup>2+</sup>-conductive channelrhodopsin.","authors":"Yujing Zhang, Jing Yu-Strzelczyk, Dmitri Sisario, Rebecca Holzapfel, Zoltan Nagy, Congfeng Xu, Chengxing Shen, Georg Nagel, Shiqiang Gao, Markus Bender","doi":"10.1038/s42003-025-08924-w","DOIUrl":"10.1038/s42003-025-08924-w","url":null,"abstract":"<p><p>Calcium signaling is crucial across various cell types, but its spatiotemporal dynamics remain difficult to study due to limited methods. Optogenetics, with its high precision, can address this challenge. In this study, we introduced the channelrhodopsin variant ChR2 XXM2.0, which exhibits high light sensitivity and enhanced Ca<sup>2+</sup> conductance in Xenopus oocytes, into bone marrow-derived megakaryocytes through viral transduction, aiming to clarify the poorly understood role of Ca<sup>2+</sup> dynamics in these cells. ChR2 XXM2.0 expression was confirmed in megakaryocyte membranes, and its functionality validated through whole-cell patch-clamp and calcium imaging. Localized activation of ChR2 XXM2.0 at the cell periphery induced cell polarization, dependent on localized calcium influx, myosin IIA, and integrin αIIbβ3-fibrinogen interaction. Furthermore, we generated a transgenic mouse line with Pf4-Cre-dependent expression of ChR2 XXM2.0, enabling optogenetic manipulation of anucleate blood platelets via light-triggered calcium signaling. Illumination induced phosphatidylserine and P-selectin exposure in spread platelets. Our results highlight the importance of asymmetric subcellular calcium events in megakaryocyte polarity and demonstrate the feasibility of manipulating platelet function using optogenetics. Taken together, our study introduces the ChR2 XXM2.0 construct and its corresponding Cre-dependent transgenic mouse line as powerful tools for manipulating subcellular Ca<sup>2+</sup> signaling, with potential applications for different cell types.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1433"},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243866","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}
引用次数: 0
Hippocampal CaMKII-α β-hydroxybutyrylation induces memory deficits in mice with type 1 diabetes mellitus. 海马CaMKII-α β-羟基丁基化诱导1型糖尿病小鼠记忆缺陷
IF 5.1 1区 生物学
Communications Biology Pub Date : 2025-10-07 DOI: 10.1038/s42003-025-08832-z
Hongchun Li, Rong Chen, Hongbo Wang, Jingwei Tian, Yinglan Zhao, Xiaobo Cen
{"title":"Hippocampal CaMKII-α β-hydroxybutyrylation induces memory deficits in mice with type 1 diabetes mellitus.","authors":"Hongchun Li, Rong Chen, Hongbo Wang, Jingwei Tian, Yinglan Zhao, Xiaobo Cen","doi":"10.1038/s42003-025-08832-z","DOIUrl":"10.1038/s42003-025-08832-z","url":null,"abstract":"<p><p>Memory loss is a manifestation of type 1 diabetes mellitus (T1DM)-induced brain damage resulting from hyperglycemia. However, the mechanism underlying T1DM-induced memory deficit remains largely unknown. In diabetes, ketogenesis occurs upon insulin deficiency, and β-hydroxybutyrate (β-OHB) is synthesized and plays a dominant role in diabetic ketoacidosis. In the present study, we investigate the effect of β-OHB-mediated lysine β-hydroxybutyrylation (kbhb) of hippocampal calcium/calmodulin-dependent kinase II-α (CaMKII-α) on memory deficits in male T1DM mice. We find that streptozotocin (STZ) induced a significant increase in the concentration of hippocampal β-OHB in T1DM mice. High β-OHB levels promote CaMKII-α kbhb at the K42 and K267 residues and further inhibit CaMKII activity. The suppression of CaMKII-α kbhb in the hippocampus via the inhibition of P300, a kbhb transferase, reverse the decrease in CaMKII activity and alleviate memory deficits in T1DM mice. Molecular dynamics (MD) simulations further reveale that the enhanced flexibility caused by CaMKII-α kbhb on the critical, conserved residue K42, which alters its side chain, in the catalytic ATP-binding site of this enzyme may be one of the factors responsible for the observed reduction enzymatic activity. Collectively, our results show that a high β-OHB concentration dysregulates hippocampal CaMKII-α kbhb, which may contribute to memory deficits in T1DM mice.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1435"},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243948","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}
引用次数: 0
OncoMark: a high-throughput neural multi-task learning framework for comprehensive cancer hallmark quantification. OncoMark:一个用于综合癌症特征量化的高通量神经多任务学习框架。
IF 5.1 1区 生物学
Communications Biology Pub Date : 2025-10-07 DOI: 10.1038/s42003-025-08727-z
Shreyansh Priyadarshi, Camellia Mazumder, Bhavesh Neekhra, Sayan Biswas, Debojyoti Chowdhury, Debayan Gupta, Shubhasis Haldar
{"title":"OncoMark: a high-throughput neural multi-task learning framework for comprehensive cancer hallmark quantification.","authors":"Shreyansh Priyadarshi, Camellia Mazumder, Bhavesh Neekhra, Sayan Biswas, Debojyoti Chowdhury, Debayan Gupta, Shubhasis Haldar","doi":"10.1038/s42003-025-08727-z","DOIUrl":"10.1038/s42003-025-08727-z","url":null,"abstract":"<p><p>Quantifying the biological processes that drive cancer progression remains a key challenge in oncology. Although the hallmarks of cancer provide a foundational framework for understanding tumor behavior, existing diagnostic tools rarely measure these hallmarks directly. Here we present a neural multi-task learning-based framework that estimates hallmark activity using gene expression data from tumor biopsies. The model was trained on transcriptomic profiles from 941 tumors spanning 14 tissue types and tested on five independent datasets. It predicts the activity of ten cancer hallmarks simultaneously and with high accuracy. Additional validation on large-scale datasets including normal and cancer samples confirmed its sensitivity and specificity. Predicted hallmark activity was associated with clinical staging, suggesting biological relevance. A web-based tool was developed to facilitate integration into research and clinical workflows. This approach enables efficient analysis of transcriptomic data to inform understanding of tumor biology and support individualized treatment strategies.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1434"},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243896","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}
引用次数: 0
Genotyping short tandem repeats across copy number alterations, aneuploidies, and polyploid organisms. 基因分型短串联重复在拷贝数改变,非整倍体和多倍体生物。
IF 5.1 1区 生物学
Communications Biology Pub Date : 2025-10-07 DOI: 10.1038/s42003-025-08837-8
Max A Verbiest, Elena Grassi, Andrea Bertotti, Maria Anisimova
{"title":"Genotyping short tandem repeats across copy number alterations, aneuploidies, and polyploid organisms.","authors":"Max A Verbiest, Elena Grassi, Andrea Bertotti, Maria Anisimova","doi":"10.1038/s42003-025-08837-8","DOIUrl":"10.1038/s42003-025-08837-8","url":null,"abstract":"<p><p>Short tandem repeats (STRs) are a rich source of genetic variation, but are difficult to genotype. While specialized repeat variant callers exist, they typically assume a euploid human genome. This means recent findings regarding phenotypic effects of STR variants in human health and disease cannot be readily extended to polyploid organisms or cancer, which is characterised by copy number alterations (CNAs). Here we present ConSTRain, a novel STR variant caller that explicitly accounts for the copy number of loci in its genotyping approach. We benchmark ConSTRain using a euploid human 100X whole genome sequencing sample where it calls STR allele lengths for over 1.7 × 10<sup>6</sup> loci in under 20 minutes with an accuracy of 98.28%. Subsequently, we show that ConSTRain resolves complex STR genotypes in an artificial trisomy 21 sample and a polyploid Dwarf Cavendish banana harbouring a large duplication. Finally, we analyse a microsatellite instable colorectal cancer tumoroid, where ConSTRain tackles CNAs and whole-genome duplications. ConSTRain is the first STR variant caller that allows for the investigation of repeats affected by CNAs, aneuploidies, and polyploid genomes. This unlocks the investigation of STRs across a wide range of contexts and organisms where they previously could not be easily studied.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1437"},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243907","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}
引用次数: 0
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