Cell Reports Methods最新文献_第8页

Precise estimation of in-depth relatedness in biobank-scale datasets using deepKin. 使用deepKin精确估计生物库规模数据集的深度相关性。

IF 4.3

Cell Reports Methods Pub Date : 2025-06-16 Epub Date: 2025-05-27 DOI: 10.1016/j.crmeth.2025.101053

Qi-Xin Zhang, Dovini Jayasinghe, Zhe Zhang, Sang Hong Lee, Hai-Ming Xu, Guo-Bo Chen

{"title":"Precise estimation of in-depth relatedness in biobank-scale datasets using deepKin.","authors":"Qi-Xin Zhang, Dovini Jayasinghe, Zhe Zhang, Sang Hong Lee, Hai-Ming Xu, Guo-Bo Chen","doi":"10.1016/j.crmeth.2025.101053","DOIUrl":"10.1016/j.crmeth.2025.101053","url":null,"abstract":"Accurate relatedness estimation is essential in biobank-scale genetic studies. We present deepKin, a method-of-moments framework that accounts for sampling variance to enable statistical inference and classification of relatedness. Unlike traditional methods using fixed thresholds, deepKin computes data-specific significance thresholds, determines the minimum effective number of markers, and estimates the statistical power to detect distant relatives. Through simulations, we demonstrate that deepKin accurately infers both unrelated pairs and relatives by leveraging sampling variance. In the UK Biobank (UKB), analysis of the 3K Oxford subset showed that SNP sets with a larger effective number of markers provided greater power for detecting distant relatives. In the White British subset, deepKin identified over 212,000 significant relative pairs, categorized into six degrees, and revealed their geographic patterns across 19 UKB assessment centers through within-cohort and cross-cohort relatedness estimation. An R package (deepKin) is available at GitHub.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101053"},"PeriodicalIF":4.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Encapsulation of protein/DNA complexes into unilamellar liposomes via annexin-mediated membrane recruitment and sonication. 通过膜联蛋白介导的膜募集和超声将蛋白质/DNA复合物封装到单层脂质体中。

IF 4.3

Cell Reports Methods Pub Date : 2025-06-16 Epub Date: 2025-06-09 DOI: 10.1016/j.crmeth.2025.101073

Michael Burger, Finn Brigger, Valeria Mantella, Jean-Christophe Leroux

引用次数: 0

An AAV capsid proposed as microglia-targeting directs genetic expression in forebrain excitatory neurons. 一种AAV衣壳被提出作为小胶质细胞靶向指导前脑兴奋性神经元的基因表达。

IF 4.5

Cell Reports Methods Pub Date : 2025-06-16 Epub Date: 2025-05-21 DOI: 10.1016/j.crmeth.2025.101054

Wenhao Cao, Zhiqun Tan, Bereket T Berackey, Jason K Nguyen, Sara R Brown, Shiyang Du, Bin Lin, Qiao Ye, Magdalene Seiler, Todd C Holmes, Xiangmin Xu

引用次数: 0

Quiescent horizontal basal stem cells act as a niche for olfactory neurogenesis in a mouse 3D organoid model. 静止水平基底干细胞在小鼠三维类器官模型中作为嗅觉神经发生的生态位。

IF 4.3

Cell Reports Methods Pub Date : 2025-06-16 Epub Date: 2025-05-28 DOI: 10.1016/j.crmeth.2025.101055

Juliana Gutschow Gameiro, Constantin A Hintschich, Agnès Dekeyser, Valérie Hox, James E Schwob, Eric H Holbrook, Marco Aurélio Fornazieri, Brian Lin

{"title":"Quiescent horizontal basal stem cells act as a niche for olfactory neurogenesis in a mouse 3D organoid model.","authors":"Juliana Gutschow Gameiro, Constantin A Hintschich, Agnès Dekeyser, Valérie Hox, James E Schwob, Eric H Holbrook, Marco Aurélio Fornazieri, Brian Lin","doi":"10.1016/j.crmeth.2025.101055","DOIUrl":"10.1016/j.crmeth.2025.101055","url":null,"abstract":"The olfactory epithelium contains two basal stem cell populations that facilitate the usually life-long ability for neuronal regeneration that is required for maintaining our sense of smell. Horizontal basal cells (HBCs) are generally quiescent and only become active after direct injury to the epithelium that eliminates more than just the olfactory sensory neurons (OSNs). Globose basal cells (GBCs) lie apical to HBCs and are solely responsible for the generation of olfactory neurons in the undamaged epithelium. Understanding how these two neurogenic stem cell populations are regulated as OSNs are replenished is hampered by a lack of robust culture models. Here, we report the development of a 3D mouse organoid model that recapitulates the neurogenic cascade, forming immature OSNs while maintaining both HBCs and GBCs in culture. We use this model to demonstrate that, despite their relative quiescence, HBCs form a critical niche for the emergence and composition of the organoid.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101055"},"PeriodicalIF":4.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mountable miniature microphones to identify and assign mouse ultrasonic vocalizations. 安装微型麦克风，以识别和分配鼠标超声波发声。

IF 4.3

Cell Reports Methods Pub Date : 2025-06-16 DOI: 10.1016/j.crmeth.2025.101081

Elena N Waidmann, Victor H Y Yang, Erica Luo, William C Doyle, Erich D Jarvis

引用次数: 0

Three-dimensional assessments are necessary to determine the true, spatially resolved composition of tissues. 三维评估是必要的，以确定组织的真实，空间分辨组成。

IF 4.3

Cell Reports Methods Pub Date : 2025-06-16 Epub Date: 2025-06-09 DOI: 10.1016/j.crmeth.2025.101075

André Forjaz, Eduarda Vaz, Valentina Matos Romero, Saurabh Joshi, Vasco Queiroga, Alicia M Braxton, Ann C Jiang, Kohei Fujikura, Toby Cornish, Seung-Mo Hong, Ralph H Hruban, Pei-Hsun Wu, Laura D Wood, Ashley L Kiemen, Denis Wirtz

{"title":"Three-dimensional assessments are necessary to determine the true, spatially resolved composition of tissues.","authors":"André Forjaz, Eduarda Vaz, Valentina Matos Romero, Saurabh Joshi, Vasco Queiroga, Alicia M Braxton, Ann C Jiang, Kohei Fujikura, Toby Cornish, Seung-Mo Hong, Ralph H Hruban, Pei-Hsun Wu, Laura D Wood, Ashley L Kiemen, Denis Wirtz","doi":"10.1016/j.crmeth.2025.101075","DOIUrl":"10.1016/j.crmeth.2025.101075","url":null,"abstract":"Methods for spatially resolved cellular profiling of tissue sections enable in-depth study of inter- and intra-sample heterogeneity but often profile small regions, requiring evaluation of many samples to compensate for limited assessment. Recent advances in three-dimensional (3D) tissue mapping offer deeper insights; however, attempts to quantify the information gained in transitioning to 3D remains limited. Here, to compare inter- and intra-sample tissue heterogeneity, we analyze >100 pancreas samples as cores, whole-slide images (WSIs), and cm3-sized 3D samples. We show that tens of WSIs and hundreds of tissue microarrays are needed to approximate the compositional tissue heterogeneity of tumors. Additionally, spatial correlations of pancreatic structures decay significantly within microns, demonstrating that isolated two-dimensional (2D) sections poorly represent their surroundings. Through 3D simulations, we determined the number of slides necessary to accurately measure tumor burden. These results quantify the power of 3D mapping and establish sampling methods for biological studies prioritizing composition or incidence.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101075"},"PeriodicalIF":4.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Harmonizing TUNEL with multiplexed iterative immunofluorescence enriches spatial contextualization of cell death. TUNEL与多路迭代免疫荧光的协调丰富了细胞死亡的空间语境化。

IF 4.3

Cell Reports Methods Pub Date : 2025-05-19 Epub Date: 2025-05-12 DOI: 10.1016/j.crmeth.2025.101047

Marc S Sherman, Thomas McMahon-Skates, Lindsey S Gaston, Sonya W Katzen, Joseph A Majzoub, Wolfram Goessling

{"title":"Harmonizing TUNEL with multiplexed iterative immunofluorescence enriches spatial contextualization of cell death.","authors":"Marc S Sherman, Thomas McMahon-Skates, Lindsey S Gaston, Sonya W Katzen, Joseph A Majzoub, Wolfram Goessling","doi":"10.1016/j.crmeth.2025.101047","DOIUrl":"10.1016/j.crmeth.2025.101047","url":null,"abstract":"Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) is an essential tool for detecting cell death in tissues, but its compatibility with spatial proteomic methods is unknown. We evaluated variations of the TUNEL protocol for compatibility with multiple iterative labeling by antibody neodeposition (MILAN) in acetaminophen-induced hepatocyte necrosis and dexamethasone-induced adrenocortical apoptosis. Using a commercial Click-iT-based assay as a standard, TUNEL signal could be reliably produced independent of the antigen retrieval method, with tissue-specific minor differences in signal to noise. In contrast, proteinase K treatment consistently reduced or even abrogated protein antigenicity, while pressure cooker treatment enhanced protein antigenicity for the targets tested. Antibody-based TUNEL with pressure cooker retrieval could be flexibly integrated into a MILAN staining series, and first-round TUNEL was also compatible with a second spatial proteomic method, cyclic immunofluorescence (CycIF). We anticipate that this harmonization of TUNEL with spatial proteomics will enhance the spatial contextualization of cell death in complex tissues.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101047"},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding how genetically encoded tags and crowding agents affect phase separation by heterochromatin protein HP1α. 了解基因编码标签和拥挤因子如何影响异染色质蛋白HP1α的相分离。

IF 4.3

Cell Reports Methods Pub Date : 2025-05-19 Epub Date: 2025-04-21 DOI: 10.1016/j.crmeth.2025.101029

Ziling Kate Zhou, Kibeom Hong, Bo Huang, Geeta J Narlikar

{"title":"Understanding how genetically encoded tags and crowding agents affect phase separation by heterochromatin protein HP1α.","authors":"Ziling Kate Zhou, Kibeom Hong, Bo Huang, Geeta J Narlikar","doi":"10.1016/j.crmeth.2025.101029","DOIUrl":"10.1016/j.crmeth.2025.101029","url":null,"abstract":"The heterochromatin protein HP1α (heterochromatin protein 1 alpha) phase separates in vitro and displays properties compatible with phase separation in cells. Phase separation of HP1α in cells is typically studied using genetically encoded fluorescent tags such as green fluorescent protein (GFP). Whether such tags affect the intrinsic phase separation properties of HP1α is understudied. We assessed how tag size and linker length affect phase separation by HP1α in vitro. GFP tags inhibited phase separation by HP1α. In contrast, an UnaG tag with a 16 amino acid glycine-glycine-serine (GGS) linker minimally perturbed HP1α phase separation in vitro and could be used to visualize HP1α dynamics in cells. We further investigated the effects of a commonly used crowding agent, polyethylene glycol (PEG). PEG induced phase separation of proteins with no propensity to phase separate under physiological buffer conditions and dampened the effects of HP1α mutations. Therefore, phase separation of biological macromolecules with PEG-containing crowding agents should be interpreted with caution.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101029"},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fluorescence microscopy through scattering media with robust matrix factorization. 荧光显微镜通过散射介质与鲁棒矩阵分解。

IF 4.3

Cell Reports Methods Pub Date : 2025-05-19 Epub Date: 2025-04-28 DOI: 10.1016/j.crmeth.2025.101031

Zijun Gao, Zhi Ling, Wenhao Liu, Keyi Han, Hongmanlin Zhang, Xuanwen Hua, Edward A Botchwey, Shu Jia

{"title":"Fluorescence microscopy through scattering media with robust matrix factorization.","authors":"Zijun Gao, Zhi Ling, Wenhao Liu, Keyi Han, Hongmanlin Zhang, Xuanwen Hua, Edward A Botchwey, Shu Jia","doi":"10.1016/j.crmeth.2025.101031","DOIUrl":"10.1016/j.crmeth.2025.101031","url":null,"abstract":"Biological tissues, as natural scattering media, inherently disrupt structural information, presenting significant challenges for optical imaging. Complex light propagation through tissue severely degrades image quality, limiting conventional fluorescence imaging techniques to superficial depths. Extracting meaningful information from random speckle patterns is, therefore, critical for deeper tissue imaging. In this study, we present RNP (robust non-negative principal matrix factorization), an approach that enables fluorescence microscopy under diverse scattering conditions. By integrating robust feature extraction with non-negativity constraints, RNP effectively addresses challenges posed by non-sparse signals and background interference in scattering tissue environments. The framework operates on a standard epi-fluorescence platform, eliminating the need for complex instrumentation or precise alignment. The results from imaging scattered cells and tissues demonstrate substantial improvements in robustness, field of view, depth of field, and image clarity. We anticipate that RNP will become a valuable tool for overcoming scattering challenges in fluorescence microscopy and driving advancements in biomedical research.","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"101031"},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generation of T cell responses against broad KRAS hotspot neoantigens for cell therapy or TCR discovery. 产生针对广泛的KRAS热点新抗原的T细胞应答，用于细胞治疗或TCR的发现。

IF 4.3

Cell Reports Methods Pub Date : 2025-05-19 Epub Date: 2025-05-12 DOI: 10.1016/j.crmeth.2025.101049

Brandon P Conn, Jared L Dietze, Christian J Yee, Margaret M Hallisey, Irais Ortiz-Caraveo, Marit M van Buuren, Richard B Gaynor, Kendra C Foley, Jaewon Choi, Vikram R Juneja

引用次数: 0