Cell Reports Methods最新文献_第2页

Deep mapping of structural perturbations to energetics enables precise TCR design. 结构扰动到能量学的深度映射使得精确的TCR设计成为可能。

IF 5.8

Cell Reports Methods Pub Date : 2026-10-19 Epub Date: 2026-08-20 DOI: 10.1016/j.crmeth.2026.101569

Shifu Luo, Songming Zhang, Ying Shi, Junjie Li, Jiaxin Cai, Ning-Yi Shao, Yi Pan, Jinyan Li

引用次数: 0

A sensitive method for profiling cell-type-specific secretomes of rare cells from complex tissues. 分析复杂组织中稀有细胞的细胞类型特异性分泌组的灵敏方法。

IF 5.8

Cell Reports Methods Pub Date : 2026-10-19 Epub Date: 2026-08-14 DOI: 10.1016/j.crmeth.2026.101552

Gergana Shipkovenska, Xuchao Lyu, Manalee Vishnu Surve, Joao A Paulo, Edward Chen, Vanshika Panchal, Brian Lin, Steven P Gygi, Wei Wei, Jonathan Z Long, Jayaraj Rajagopal

引用次数: 0

SwitchClass distinguishes baseline- and perturbation-aligned features across intermediate molecular states. SwitchClass区分了中间分子状态的基线和微扰特征。

IF 5.8

Cell Reports Methods Pub Date : 2026-10-19 Epub Date: 2026-08-12 DOI: 10.1016/j.crmeth.2026.101547

Di Xiao, Siqu Long, Pengyi Yang

{"title":"SwitchClass distinguishes baseline- and perturbation-aligned features across intermediate molecular states.","authors":"Di Xiao, Siqu Long, Pengyi Yang","doi":"10.1016/j.crmeth.2026.101547","DOIUrl":"10.1016/j.crmeth.2026.101547","url":null,"abstract":"Biological systems often exhibit intermediate molecular states under perturbation, showing changes that align with baseline condition or perturbed state. Capturing these complex patterns is critical for understanding molecular resilience and maladaptive persistence. We introduce SwitchClass, a label-switch classification framework that distinguishes features whose intermediate-state profiles align with baseline or perturbed condition. By training a dual classifier with inverted labels, SwitchClass computes a directional importance score (δ), which quantifies each feature's alignment across biological states. Applied to colorectal cancer proteomics, SwitchClass reveals proteins that normalize after therapy and those remaining dysregulated, uncovering partial molecular recovery. In dietary perturbation and reversal phosphoproteomics, it uncovers the phosphorylation sites linked to incomplete restoration of insulin signaling. In single-cell transcriptomes from COVID-19 patients with varying severities, it identifies cell-type-specific transcripts marking resolution or persistence of inflammatory activity. Together, these analyses demonstrate SwitchClass as an interpretable framework for mapping directional molecular changes in systems with intermediate states.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101547"},"PeriodicalIF":5.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep learning-driven multiplexed mycotoxin detection via color-size encoded microbead imaging. 基于颜色大小编码微珠成像的深度学习驱动多路霉菌毒素检测。

IF 5.8

Cell Reports Methods Pub Date : 2026-10-19 Epub Date: 2026-08-14 DOI: 10.1016/j.crmeth.2026.101548

Xianfeng Lin, Lixin Kang, Jiaqi Feng, Meihua Dong, Nuo Duan, Zhouping Wang, Shijia Wu

{"title":"Deep learning-driven multiplexed mycotoxin detection via color-size encoded microbead imaging.","authors":"Xianfeng Lin, Lixin Kang, Jiaqi Feng, Meihua Dong, Nuo Duan, Zhouping Wang, Shijia Wu","doi":"10.1016/j.crmeth.2026.101548","DOIUrl":"10.1016/j.crmeth.2026.101548","url":null,"abstract":"Mycotoxins pose severe threats to food safety and public health, especially with synergistic toxicity from co-contamination. Herein, a deep learning-driven two-dimensional (2D)-encoded single microbead imaging decoding platform is developed for homogeneous analysis of four mycotoxins. The aptamer-recognition-triggered DNAzyme walker-hybridization chain reaction (Dz-HCR) cascade design enables direct fluorescent signal lighting and amplification on microbeads, avoiding complex separation and signal probe preparation. By leveraging two different-sized microbeads and two fluorophores modified at HCR hairpins, an ingenious color-size 2D-encoding strategy is established for high-throughput analysis. The YOLOv11 deep learning model enables rapid, accurate decoding and analysis of fluorescence images with multi-dimensional information, improving data processing efficiency. This platform exhibits high sensitivity (<1 pg/mL), wide linear ranges, and excellent specificity. The desirable spiked recovery (85.6%-114.0%) in maize and plant-based meat analogs and the consistency with HPLC-MS/MS confirm practical applicability. This method provides a promising strategy for high-throughput mycotoxin detection in food safety monitoring.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101548"},"PeriodicalIF":5.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Strategic enhancement of Cas9 nickase-driven gene amplification. Cas9镍酶驱动基因扩增的战略性增强。

IF 5.8

Cell Reports Methods Pub Date : 2026-10-19 Epub Date: 2026-08-06 DOI: 10.1016/j.crmeth.2026.101544

Hiroaki Takesue, Satoshi Okada, Takashi Ito

引用次数: 0

Calibrated simulations for dynamic focusing of ultrasound through the temporal window. 超声通过时间窗动态聚焦的校准模拟。

IF 5.8

Cell Reports Methods Pub Date : 2026-10-19 Epub Date: 2026-08-14 DOI: 10.1016/j.crmeth.2026.101568

Ehsan Dadgar-Kiani, Vibha Hebbale, Malachy W Newman, Grace Attalla, John L Alvarez, Suraya Dunsford, Kevin A Caulfield, Cameron H Good, Andrew D Krystal, Leo P Sugrue, Joline M Fan, Elsa Fouragnan, Charles F Caskey, Samuel Pichardo, Kim Butts Pauly, Keith R Murphy

{"title":"Calibrated simulations for dynamic focusing of ultrasound through the temporal window.","authors":"Ehsan Dadgar-Kiani, Vibha Hebbale, Malachy W Newman, Grace Attalla, John L Alvarez, Suraya Dunsford, Kevin A Caulfield, Cameron H Good, Andrew D Krystal, Leo P Sugrue, Joline M Fan, Elsa Fouragnan, Charles F Caskey, Samuel Pichardo, Kim Butts Pauly, Keith R Murphy","doi":"10.1016/j.crmeth.2026.101568","DOIUrl":"10.1016/j.crmeth.2026.101568","url":null,"abstract":"Focused ultrasound can be delivered through the temporal window to modulate heterogeneously located brain areas. Acoustic simulations allow for safety assessments when dynamically targeting brain structures, but the mismatch between simulation and measured focal pressure can vary across the steerable range due to mechanically inaccurate assumptions made about the skull and transducer. Here, we describe efficient methods for simulation-measurement calibration using axisymmetric projections and sparse sampling across a 3D steerable subspace encompassing deep brain targets across 157 subjects. To address the simulation-reality mismatch in skull transmission, we used the measured and predicted pressure values through eight human temporal window fragments to derive an optimized bone attenuation coefficient. Collectively, the calibration framework and optimized temporal window coefficients can be used broadly across studies to improve the accuracy of reporting and dependent safety assessment for personalized neuromodulation treatments.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101568"},"PeriodicalIF":5.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mesenchymal stem cell-derived liver-on-a-chip reconstitutes human liver structure and function. 间充质干细胞衍生的肝脏芯片重建了人类肝脏的结构和功能。

IF 5.8

Cell Reports Methods Pub Date : 2026-10-19 Epub Date: 2026-08-10 DOI: 10.1016/j.crmeth.2026.101545

Anastasia Brooks, Haotian Yang, Deborah S Barkauskas, Supun Ranaweera, Da Zou, Sally Goh, Qi Ruan, Kim Bridle, Darrell H G Crawford, Xin Liu, Michael S Roberts, Michael R Doran, Xiaowen Liang, Chun-Xia Zhao, Haolu Wang

{"title":"Mesenchymal stem cell-derived liver-on-a-chip reconstitutes human liver structure and function.","authors":"Anastasia Brooks, Haotian Yang, Deborah S Barkauskas, Supun Ranaweera, Da Zou, Sally Goh, Qi Ruan, Kim Bridle, Darrell H G Crawford, Xin Liu, Michael S Roberts, Michael R Doran, Xiaowen Liang, Chun-Xia Zhao, Haolu Wang","doi":"10.1016/j.crmeth.2026.101545","DOIUrl":"10.1016/j.crmeth.2026.101545","url":null,"abstract":"An in vitro model of human liver with functional integrity would advance liver research and enable personalized therapeutics. A microfluidic liver-on-a-chip can generate a functional hepatobiliary network using human liver cells and recapitulate blood circulation and bile excretion. However, many current microfluidic liver models lack a biliary component and cannot fully recapitulate the excretory function of the human liver. Here, we develop a microfluidic liver-on-a-chip incorporating functional endothelial cells, hepatocytes, and cholangiocytes derived from a single source of human mesenchymal stem cells. This stem cell-derived liver-on-a-chip reconstructs a simplified liver unit, including a sinusoid, a hepatocyte compartment, and a bile duct supported by barrier integrity and fluid flow. It reproduces integrated organ-level responses to xenobiotics, including hepatic uptake and biliary excretion, and models ischemic liver injury with therapeutic cell recruitment. This technology expands personalized organ-level modeling and holds strong potential for studying tissue development and advancing targeted therapies for liver injury.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101545"},"PeriodicalIF":5.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AAV-DJ enables efficient, function-preserving neuronal transduction for circuit interrogation in human cortical and thalamic organoids. AAV-DJ在人类皮层和丘脑类器官中实现有效的、功能保留的神经转导。

IF 5.8

Cell Reports Methods Pub Date : 2026-10-19 Epub Date: 2026-08-13 DOI: 10.1016/j.crmeth.2026.101546

Shota Adachi, Masatoshi Nishimura, Kosuke Yamaguchi, Akinori Y Sato, Ryosuke F Takeuchi, Fumitaka Osakada

{"title":"AAV-DJ enables efficient, function-preserving neuronal transduction for circuit interrogation in human cortical and thalamic organoids.","authors":"Shota Adachi, Masatoshi Nishimura, Kosuke Yamaguchi, Akinori Y Sato, Ryosuke F Takeuchi, Fumitaka Osakada","doi":"10.1016/j.crmeth.2026.101546","DOIUrl":"10.1016/j.crmeth.2026.101546","url":null,"abstract":"Neural organoids provide tractable models of human brain development, function, and disease, but adeno-associated viral vector (AAV)-based gene delivery is limited by inefficient transduction and insufficient comparative evaluation of the natural and engineered capsids. Here, we evaluated seven AAV capsids (AAV-2, -6, -9, -DJ, -2-retro, -PHP.eB, and -Cap-Mac) for transduction efficiency, cell type tropism, cytotoxicity, and functional integrity in human cortical and thalamic organoids. AAV-Cap-Mac demonstrated the highest transduction efficiency, with broad cellular tropism, but caused cytotoxicity and decreased neuronal activity. By contrast, AAV-DJ yielded efficient neuronal transduction, with preserved calcium dynamics and minimal cytotoxicity, which enabled rabies virus-based circuit tracing and all-optical physiology. Our findings reveal a capsid-dependent trade-off between transduction efficiency and functional integrity and identify AAV-DJ as an optimal serotype for robust gene delivery and physiological interrogation in organoid-based neuroscience. Combining AAV-DJ with emerging molecular and circuit-level technologies in organoids should facilitate mechanistic and translational studies of the human brain.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101546"},"PeriodicalIF":5.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Improving computational tumor ploidy estimation in complex cancer genomes through flow-cytometry-guided calibration. 通过流式细胞术引导校准改进复杂癌症基因组的计算肿瘤倍性估计。

IF 5.8

Cell Reports Methods Pub Date : 2026-10-19 Epub Date: 2026-08-31 DOI: 10.1016/j.crmeth.2026.101570

Thomas Butters, Dahmane Oukrif, Punn Tannirandorn, Ianthe Aem van Belzen, Jianan Chen, Christopher Davies, Runtian Lin, Solange De Noon, Dalil Taher, Chloe Cutler, Mark Markov, Anna Tollit, Fatine Oumlil, Christopher D Steele, Matthew Fittall, Yanping Guo, Isidro Cortés-Ciriano, Peter Van Loo, Adrienne M Flanagan, Nischalan Pillay, Maxime Tarabichi

{"title":"Improving computational tumor ploidy estimation in complex cancer genomes through flow-cytometry-guided calibration.","authors":"Thomas Butters, Dahmane Oukrif, Punn Tannirandorn, Ianthe Aem van Belzen, Jianan Chen, Christopher Davies, Runtian Lin, Solange De Noon, Dalil Taher, Chloe Cutler, Mark Markov, Anna Tollit, Fatine Oumlil, Christopher D Steele, Matthew Fittall, Yanping Guo, Isidro Cortés-Ciriano, Peter Van Loo, Adrienne M Flanagan, Nischalan Pillay, Maxime Tarabichi","doi":"10.1016/j.crmeth.2026.101570","DOIUrl":"10.1016/j.crmeth.2026.101570","url":null,"abstract":"DNA ploidy is an important predictor of tumor behavior and prognosis, and its accurate estimation is essential for robust genomic analysis in translational cancer research and diagnostics. However, the most common in silico methods for ploidy estimation using next-generation-sequencing-based copy-number aberration (CNA)-calling algorithms are often inaccurate due to inherent ambiguity in fitting ploidy solutions. This study evaluates the accuracy of state-of-the-art CNA callers using whole-genome sequencing by comparing their ploidy estimates with gold-standard ploidy measurements derived by flow cytometry (FC). We demonstrate that CNA callers are up to 38% inaccurate in cancers with complex genomes, which impacts the accurate estimation of copy number of cancer genes and could have clinical implications and impacts on inferences of tumor evolution. Critically, flow-cytometry-based calibration of CNA callers yields highly accurate ploidy estimates (ρPearson = 0.92, p < 0.001), providing a robust solution to the substantial inaccuracies that compromise clinical decision-making and evolutionary inference in complex cancers.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101570"},"PeriodicalIF":5.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Volumetric denoising enables high-throughput volume electron microscopy and efficient downstream analysis. 体积去噪可实现高通量体积电子显微镜和高效下游分析。

IF 5.8

Cell Reports Methods Pub Date : 2026-10-19 Epub Date: 2026-08-04 DOI: 10.1016/j.crmeth.2026.101543

Bohao Chen, Fangfang Wang, Haoyu Wang, Yanchao Zhang, Zhuangzhuang Zhao, Haoran Chen, Hua Han, Xi Chen, Yunfeng Hua

{"title":"Volumetric denoising enables high-throughput volume electron microscopy and efficient downstream analysis.","authors":"Bohao Chen, Fangfang Wang, Haoyu Wang, Yanchao Zhang, Zhuangzhuang Zhao, Haoran Chen, Hua Han, Xi Chen, Yunfeng Hua","doi":"10.1016/j.crmeth.2026.101543","DOIUrl":"10.1016/j.crmeth.2026.101543","url":null,"abstract":"Volume electron microscopy (VEM) enables nanometer-resolution three-dimensional (3D) visualization of biological specimens via serial sectioning and imaging. Owing to limitations of downstream analysis, VEM datasets are often acquired at slow speeds and high resolutions, thereby limiting achievable imaging throughput. By systematically searching for optimal VEM acquisition conditions, we find that sufficient spatial resolution effectively counteracts high image noise in preserving 3D structural information. To further verify that denoising is more effective in restoring volumetric datasets than axial interpolation, we compared machine learning-based methods, including a newly developed 3D context-based denoising model, through various tasks on VEM datasets acquired simultaneously. Our volumetric approach not only outperforms other baseline methods in faithful feature recovery but also facilitates robust serial block-face cutting down to 20 nm by allowing fast imaging. This work provides both an optimized acquisition strategy and volumetric denoising methods as actionable guidelines for maximizing VEM throughput.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101543"},"PeriodicalIF":5.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0