Cell Reports Methods最新文献

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A gray box framework that optimizes a white box logical model using a black box optimizer for simulating cellular responses to perturbations. 灰盒框架,利用黑盒优化器优化白盒逻辑模型,模拟细胞对扰动的反应。
IF 3.8
Cell Reports Methods Pub Date : 2024-05-20 Epub Date: 2024-05-13 DOI: 10.1016/j.crmeth.2024.100773
Yunseong Kim, Younghyun Han, Corbin Hopper, Jonghoon Lee, Jae Il Joo, Jeong-Ryeol Gong, Chun-Kyung Lee, Seong-Hoon Jang, Junsoo Kang, Taeyoung Kim, Kwang-Hyun Cho
{"title":"A gray box framework that optimizes a white box logical model using a black box optimizer for simulating cellular responses to perturbations.","authors":"Yunseong Kim, Younghyun Han, Corbin Hopper, Jonghoon Lee, Jae Il Joo, Jeong-Ryeol Gong, Chun-Kyung Lee, Seong-Hoon Jang, Junsoo Kang, Taeyoung Kim, Kwang-Hyun Cho","doi":"10.1016/j.crmeth.2024.100773","DOIUrl":"10.1016/j.crmeth.2024.100773","url":null,"abstract":"<p><p>Predicting cellular responses to perturbations requires interpretable insights into molecular regulatory dynamics to perform reliable cell fate control, despite the confounding non-linearity of the underlying interactions. There is a growing interest in developing machine learning-based perturbation response prediction models to handle the non-linearity of perturbation data, but their interpretation in terms of molecular regulatory dynamics remains a challenge. Alternatively, for meaningful biological interpretation, logical network models such as Boolean networks are widely used in systems biology to represent intracellular molecular regulation. However, determining the appropriate regulatory logic of large-scale networks remains an obstacle due to the high-dimensional and discontinuous search space. To tackle these challenges, we present a scalable derivative-free optimizer trained by meta-reinforcement learning for Boolean network models. The logical network model optimized by the trained optimizer successfully predicts anti-cancer drug responses of cancer cell lines, while simultaneously providing insight into their underlying molecular regulatory mechanisms.</p>","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"100773"},"PeriodicalIF":3.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923518","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
Precision nanoscale patterning of TLR ligands for improved cancer immunotherapy. 对 TLR 配体进行精确的纳米级图案化,以改进癌症免疫疗法。
IF 3.8
Cell Reports Methods Pub Date : 2024-05-20 DOI: 10.1016/j.crmeth.2024.100782
Chung Yi Tseng, Farshad Murtada, Leo Y T Chou
{"title":"Precision nanoscale patterning of TLR ligands for improved cancer immunotherapy.","authors":"Chung Yi Tseng, Farshad Murtada, Leo Y T Chou","doi":"10.1016/j.crmeth.2024.100782","DOIUrl":"10.1016/j.crmeth.2024.100782","url":null,"abstract":"<p><p>In a recent issue of Nature Nanotechnology, Zeng et al. report that arraying immuno-stimulatory CpG molecules with specific nanoscale spacing on DNA origami nanoparticles enhanced Th1-polarized immune responses. These results highlight spatial presentation of adjuvants as a design strategy to optimize cancer vaccine efficacy, safety, and tolerability.</p>","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":"4 5","pages":"100782"},"PeriodicalIF":3.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076974","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
A computational tool suite to facilitate single-cell lineage tracing analyses. 促进单细胞系谱追踪分析的计算工具套件。
IF 3.8
Cell Reports Methods Pub Date : 2024-05-20 Epub Date: 2024-05-13 DOI: 10.1016/j.crmeth.2024.100780
Joshua J Waterfall, Adil Midoun, Leïla Perié
{"title":"A computational tool suite to facilitate single-cell lineage tracing analyses.","authors":"Joshua J Waterfall, Adil Midoun, Leïla Perié","doi":"10.1016/j.crmeth.2024.100780","DOIUrl":"10.1016/j.crmeth.2024.100780","url":null,"abstract":"<p><p>Tracking the lineage relationships of cell populations is of increasing interest in diverse biological contexts. In this issue of Cell Reports Methods, Holze et al. present a suite of computational tools to facilitate such analyses and encourage their broader application.</p>","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"100780"},"PeriodicalIF":3.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923516","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
Effective cryopreservation of human brain tissue and neural organoids. 有效冷冻保存人类脑组织和神经器官组织。
IF 3.8
Cell Reports Methods Pub Date : 2024-05-20 Epub Date: 2024-05-13 DOI: 10.1016/j.crmeth.2024.100777
Weiwei Xue, Huijuan Li, Jinhong Xu, Xiao Yu, Linlin Liu, Huihui Liu, Rui Zhao, Zhicheng Shao
{"title":"Effective cryopreservation of human brain tissue and neural organoids.","authors":"Weiwei Xue, Huijuan Li, Jinhong Xu, Xiao Yu, Linlin Liu, Huihui Liu, Rui Zhao, Zhicheng Shao","doi":"10.1016/j.crmeth.2024.100777","DOIUrl":"10.1016/j.crmeth.2024.100777","url":null,"abstract":"<p><p>Human brain tissue models and organoids are vital for studying and modeling human neurological disease. However, the high cost of long-term cultured organoids inhibits their wide-ranging application. It is therefore urgent to develop methods for the cryopreservation of brain tissue and organoids. Here, we establish a method using methylcellulose, ethylene glycol, DMSO, and Y27632 (termed MEDY) for the cryopreservation of cortical organoids without disrupting the neural cytoarchitecture or functional activity. MEDY can be applied to multiple brain-region-specific organoids, including the dorsal/ventral forebrain, spinal cord, optic vesicle brain, and epilepsy patient-derived brain organoids. Additionally, MEDY enables the cryopreservation of human brain tissue samples, and pathological features are retained after thawing. Transcriptomic analysis shows that MEDY can protect synaptic function and inhibit the endoplasmic reticulum-mediated apoptosis pathway. MEDY will enable the large-scale and reliable storage of diverse neural organoids and living brain tissue and will facilitate wide-ranging research, medical applications, and drug screening.</p>","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"100777"},"PeriodicalIF":3.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923523","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
Interactions-based classification of a single microbial sample. 基于相互作用的单一微生物样本分类。
IF 3.8
Cell Reports Methods Pub Date : 2024-05-20 Epub Date: 2024-05-13 DOI: 10.1016/j.crmeth.2024.100775
Yogev Yonatan, Shaya Kahn, Amir Bashan
{"title":"Interactions-based classification of a single microbial sample.","authors":"Yogev Yonatan, Shaya Kahn, Amir Bashan","doi":"10.1016/j.crmeth.2024.100775","DOIUrl":"10.1016/j.crmeth.2024.100775","url":null,"abstract":"<p><p>To address the limitation of overlooking crucial ecological interactions due to relying on single time point samples, we developed a computational approach that analyzes individual samples based on the interspecific microbial relationships. We verify, using both numerical simulations as well as real and shuffled microbial profiles from the human oral cavity, that the method can classify single samples based on their interspecific interactions. By analyzing the gut microbiome of people with autistic spectrum disorder, we found that our interaction-based method can improve the classification of individual subjects based on a single microbial sample. These results demonstrate that the underlying ecological interactions can be practically utilized to facilitate microbiome-based diagnosis and precision medicine.</p>","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"100775"},"PeriodicalIF":3.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923524","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
A platform for rapid patient-derived cutaneous neurofibroma organoid establishment and screening. 快速建立和筛选源自患者的皮肤神经纤维瘤类器官的平台。
IF 3.8
Cell Reports Methods Pub Date : 2024-05-20 Epub Date: 2024-05-13 DOI: 10.1016/j.crmeth.2024.100772
Huyen Thi Lam Nguyen, Emily Kohl, Jessica Bade, Stefan E Eng, Anela Tosevska, Ahmad Al Shihabi, Peyton J Tebon, Jenny J Hong, Sarah Dry, Paul C Boutros, Andre Panossian, Sara J C Gosline, Alice Soragni
{"title":"A platform for rapid patient-derived cutaneous neurofibroma organoid establishment and screening.","authors":"Huyen Thi Lam Nguyen, Emily Kohl, Jessica Bade, Stefan E Eng, Anela Tosevska, Ahmad Al Shihabi, Peyton J Tebon, Jenny J Hong, Sarah Dry, Paul C Boutros, Andre Panossian, Sara J C Gosline, Alice Soragni","doi":"10.1016/j.crmeth.2024.100772","DOIUrl":"10.1016/j.crmeth.2024.100772","url":null,"abstract":"<p><p>Localized cutaneous neurofibromas (cNFs) are benign tumors that arise in the dermis of patients affected by neurofibromatosis type 1 syndrome. cNFs are benign lesions: they do not undergo malignant transformation or metastasize. Nevertheless, they can cover a significant proportion of the body, with some individuals developing hundreds to thousands of lesions. cNFs can cause pain, itching, and disfigurement resulting in substantial socio-emotional repercussions. Currently, surgery and laser desiccation are the sole treatment options but may result in scarring and potential regrowth from incomplete removal. To identify effective systemic therapies, we introduce an approach to establish and screen cNF organoids. We optimized conditions to support the ex vivo growth of genomically diverse cNFs. Patient-derived cNF organoids closely recapitulate cellular and molecular features of parental tumors as measured by immunohistopathology, methylation, RNA sequencing, and flow cytometry. Our cNF organoid platform enables rapid screening of hundreds of compounds in a patient- and tumor-specific manner.</p>","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"100772"},"PeriodicalIF":3.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923519","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
Modeling alcohol-associated liver disease in humans using adipose stromal or stem cell-derived organoids. 利用脂肪基质或干细胞衍生的器官组织模拟人类酒精相关性肝病。
IF 3.8
Cell Reports Methods Pub Date : 2024-05-20 Epub Date: 2024-05-14 DOI: 10.1016/j.crmeth.2024.100778
Guoyun Bi, Xuan Zhang, Weihong Li, Xin Lu, Xu He, Yaqiong Li, Rixing Bai, Haiyan Zhang
{"title":"Modeling alcohol-associated liver disease in humans using adipose stromal or stem cell-derived organoids.","authors":"Guoyun Bi, Xuan Zhang, Weihong Li, Xin Lu, Xu He, Yaqiong Li, Rixing Bai, Haiyan Zhang","doi":"10.1016/j.crmeth.2024.100778","DOIUrl":"10.1016/j.crmeth.2024.100778","url":null,"abstract":"<p><p>Alcohol-associated liver disease (ALD) is a prevalent liver disease, yet research is hampered by the lack of suitable and reliable human ALD models. Herein, we generated human adipose stromal/stem cell (hASC)-derived hepatocellular organoids (hAHOs) and hASC-derived liver organoids (hALOs) in a three-dimensional system using hASC-derived hepatocyte-like cells and endodermal progenitor cells, respectively. The hAHOs were composed of major hepatocytes and cholangiocytes. The hALOs contained hepatocytes and nonparenchymal cells and possessed a more mature liver function than hAHOs. Upon ethanol treatment, both steatosis and inflammation were present in hAHOs and hALOs. The incubation of hALOs with ethanol resulted in increases in the levels of oxidative stress, the endoplasmic reticulum protein thioredoxin domain-containing protein 5 (TXNDC5), the alcohol-metabolizing enzymes ADH1B and ALDH1B1, and extracellular matrix accumulation, similar to those of liver tissues from patients with ALD. These results present a useful approach for understanding the pathogenesis of ALD in humans, thus facilitating the discovery of effective treatments.</p>","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"100778"},"PeriodicalIF":3.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946140","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
Systematic analysis of proteome turnover in an organoid model of pancreatic cancer by dSILO. 利用 dSILO 系统分析胰腺癌类器官模型中蛋白质组的周转。
IF 3.8
Cell Reports Methods Pub Date : 2024-05-20 Epub Date: 2024-04-26 DOI: 10.1016/j.crmeth.2024.100760
Alison B Ross, Darvesh Gorhe, Jenny Kim Kim, Stefanie Hodapp, Lela DeVine, Karina M Chan, Iok In Christine Chio, Marko Jovanovic, Marina Ayres Pereira
{"title":"Systematic analysis of proteome turnover in an organoid model of pancreatic cancer by dSILO.","authors":"Alison B Ross, Darvesh Gorhe, Jenny Kim Kim, Stefanie Hodapp, Lela DeVine, Karina M Chan, Iok In Christine Chio, Marko Jovanovic, Marina Ayres Pereira","doi":"10.1016/j.crmeth.2024.100760","DOIUrl":"10.1016/j.crmeth.2024.100760","url":null,"abstract":"<p><p>The role of protein turnover in pancreatic ductal adenocarcinoma (PDA) metastasis has not been previously investigated. We introduce dynamic stable-isotope labeling of organoids (dSILO): a dynamic SILAC derivative that combines a pulse of isotopically labeled amino acids with isobaric tandem mass-tag (TMT) labeling to measure proteome-wide protein turnover rates in organoids. We applied it to a PDA model and discovered that metastatic organoids exhibit an accelerated global proteome turnover compared to primary tumor organoids. Globally, most turnover changes are not reflected at the level of protein abundance. Interestingly, the group of proteins that show the highest turnover increase in metastatic PDA compared to tumor is involved in mitochondrial respiration. This indicates that metastatic PDA may adopt alternative respiratory chain functionality that is controlled by the rate at which proteins are turned over. Collectively, our analysis of proteome turnover in PDA organoids offers insights into the mechanisms underlying PDA metastasis.</p>","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"100760"},"PeriodicalIF":3.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874809","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
Optimizing the conversion of phosphoenolpyruvate to lactate by enzymatic channeling with mixed nanoparticle display. 通过混合纳米粒子显示的酶通道优化磷酸烯醇丙酮酸到乳酸的转化。
IF 3.8
Cell Reports Methods Pub Date : 2024-05-20 Epub Date: 2024-05-06 DOI: 10.1016/j.crmeth.2024.100764
Shelby L Hooe, Christopher M Green, Kimihiro Susumu, Michael H Stewart, Joyce C Breger, Igor L Medintz
{"title":"Optimizing the conversion of phosphoenolpyruvate to lactate by enzymatic channeling with mixed nanoparticle display.","authors":"Shelby L Hooe, Christopher M Green, Kimihiro Susumu, Michael H Stewart, Joyce C Breger, Igor L Medintz","doi":"10.1016/j.crmeth.2024.100764","DOIUrl":"10.1016/j.crmeth.2024.100764","url":null,"abstract":"<p><p>Co-assembling enzymes with nanoparticles (NPs) into nanoclusters allows them to access channeling, a highly efficient form of multienzyme catalysis. Using pyruvate kinase (PykA) and lactate dehydrogenase (LDH) to convert phosphoenolpyruvic acid to lactic acid with semiconductor quantum dots (QDs) confirms how enzyme cluster formation dictates the rate of coupled catalytic flux (k<sub>flux</sub>) across a series of differentially sized/shaped QDs and 2D nanoplatelets (NPLs). Enzyme kinetics and coupled flux were used to demonstrate that by mixing different NP systems into clusters, a >10× improvement in k<sub>flux</sub> is observed relative to free enzymes, which is also ≥2× greater than enhancement on individual NPs. Cluster formation was characterized with gel electrophoresis and transmission electron microscopy (TEM) imaging. The generalizability of this mixed-NP approach to improving flux is confirmed by application to a seven-enzyme system. This represents a powerful approach for accessing channeling with almost any choice of enzymes constituting a multienzyme cascade.</p>","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"100764"},"PeriodicalIF":3.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877466","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
Analyzing the functional effects of DNA variants with gene editing. 通过基因编辑分析 DNA 变异的功能效应。
IF 3.8
Cell Reports Methods Pub Date : 2024-05-20 Epub Date: 2024-05-13 DOI: 10.1016/j.crmeth.2024.100776
Sarah Cooper, Sofia Obolenski, Andrew J Waters, Andrew R Bassett, Matthew A Coelho
{"title":"Analyzing the functional effects of DNA variants with gene editing.","authors":"Sarah Cooper, Sofia Obolenski, Andrew J Waters, Andrew R Bassett, Matthew A Coelho","doi":"10.1016/j.crmeth.2024.100776","DOIUrl":"10.1016/j.crmeth.2024.100776","url":null,"abstract":"<p><p>Continual advancements in genomics have led to an ever-widening disparity between the rate of discovery of genetic variants and our current understanding of their functions and potential roles in disease. Systematic methods for phenotyping DNA variants are required to effectively translate genomics data into improved outcomes for patients with genetic diseases. To make the biggest impact, these approaches must be scalable and accurate, faithfully reflect disease biology, and define complex disease mechanisms. We compare current methods to analyze the function of variants in their endogenous DNA context using genome editing strategies, such as saturation genome editing, base editing and prime editing. We discuss how these technologies can be linked to high-content readouts to gain deep mechanistic insights into variant effects. Finally, we highlight key challenges that need to be addressed to bridge the genotype to phenotype gap, and ultimately improve the diagnosis and treatment of genetic diseases.</p>","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":" ","pages":"100776"},"PeriodicalIF":3.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923521","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
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