ACS Combinatorial Science最新文献

Multi-omics with dynamic network biomarker algorithm prefigures organ-specific metastasis of lung adenocarcinoma 多组学与动态网络生物标记物算法预示肺腺癌的器官特异性转移

IF 16.6 3区化学

ACS Combinatorial Science Pub Date : 2024-11-14 DOI: 10.1038/s41467-024-53849-3

Xiaoshen Zhang, Kai Xiao, Yaokai Wen, Fengying Wu, Guanghui Gao, Luonan Chen, Caicun Zhou

{"title":"Multi-omics with dynamic network biomarker algorithm prefigures organ-specific metastasis of lung adenocarcinoma","authors":"Xiaoshen Zhang, Kai Xiao, Yaokai Wen, Fengying Wu, Guanghui Gao, Luonan Chen, Caicun Zhou","doi":"10.1038/s41467-024-53849-3","DOIUrl":"https://doi.org/10.1038/s41467-024-53849-3","url":null,"abstract":"Efficacious strategies for early detection of lung cancer metastasis are of significance for improving the survival of lung cancer patients. Here we show the marker genes and serum secretome foreshadowing the lung cancer site-specific metastasis through dynamic network biomarker (DNB) algorithm, utilizing two clinical cohorts of four major types of lung cancer distant metastases, with single-cell RNA sequencing (scRNA-seq) of primary lesions and liquid chromatography-mass spectrometry data of sera. Also, we locate the intermediate status of cancer cells, along with its gene signatures, in each metastatic state trajectory that cancer cells at this stage still have no specific organotropism. Furthermore, an integrated neural network model based on the filtered scRNA-seq data is successfully constructed and validated to predict the metastatic state trajectory of cancer cells. Overall, our study provides an insight to locate the pre-metastasis status of lung cancer and primarily examines its clinical application value, contributing to the early detection of lung cancer metastasis in a more feasible and efficacious way.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"3 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dyna-vivo-seq unveils cellular RNA dynamics during acute kidney injury via in vivo metabolic RNA labeling-based scRNA-seq 通过基于体内代谢 RNA 标记的 scRNA-seq，Dyna-vivo-seq 揭示急性肾损伤期间的细胞 RNA 动态变化

IF 16.6 3区化学

ACS Combinatorial Science Pub Date : 2024-11-14 DOI: 10.1038/s41467-024-54202-4

Kun Yin, Yiling Xu, Ye Guo, Zhong Zheng, Xinrui Lin, Meijuan Zhao, He Dong, Dianyi Liang, Zhi Zhu, Junhua Zheng, Shichao Lin, Jia Song, Chaoyong Yang

{"title":"Dyna-vivo-seq unveils cellular RNA dynamics during acute kidney injury via in vivo metabolic RNA labeling-based scRNA-seq","authors":"Kun Yin, Yiling Xu, Ye Guo, Zhong Zheng, Xinrui Lin, Meijuan Zhao, He Dong, Dianyi Liang, Zhi Zhu, Junhua Zheng, Shichao Lin, Jia Song, Chaoyong Yang","doi":"10.1038/s41467-024-54202-4","DOIUrl":"https://doi.org/10.1038/s41467-024-54202-4","url":null,"abstract":"A fundamental objective of genomics is to track variations in gene expression program. While metabolic RNA labeling-based single-cell RNA sequencing offers insights into temporal biological processes, its limited applicability only to in vitro models challenges the study of in vivo gene expression dynamics. Herein, we introduce Dyna-vivo-seq, a strategy that enables time-resolved dynamic transcription profiling in vivo at the single-cell level by examining new and old RNAs. The new RNAs can offer an additional dimension to reveal cellular heterogeneity. Leveraging new RNAs, we discern two distinct high and low metabolic labeling populations among proximal tubular (PT) cells. Furthermore, we identify 90 rapidly responding transcription factors during the acute kidney injury in female mice, highlighting that high metabolic labeling PT cells exhibit heightened susceptibility to injury. Dyna-vivo-seq provides a powerful tool for the characterization of dynamic transcriptome at the single-cell level in living organism and holds great promise for biomedical applications.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"17 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reintroduction of resistant frogs facilitates landscape-scale recovery in the presence of a lethal fungal disease 重新引入抗性青蛙有助于在出现致命真菌疾病时实现景观范围的恢复

IF 16.6 3区化学

ACS Combinatorial Science Pub Date : 2024-11-14 DOI: 10.1038/s41467-024-53608-4

Roland A. Knapp, Mark Q. Wilber, Maxwell B. Joseph, Thomas C. Smith, Robert L. Grasso

{"title":"Reintroduction of resistant frogs facilitates landscape-scale recovery in the presence of a lethal fungal disease","authors":"Roland A. Knapp, Mark Q. Wilber, Maxwell B. Joseph, Thomas C. Smith, Robert L. Grasso","doi":"10.1038/s41467-024-53608-4","DOIUrl":"https://doi.org/10.1038/s41467-024-53608-4","url":null,"abstract":"Vast alteration of the biosphere by humans is causing a sixth mass extinction, driven in part by an increase in infectious diseases. The emergence of the lethal fungal pathogen Batrachochytrium dendrobatidis (Bd) has devastated global amphibian biodiversity. Given the lack of any broadly applicable methods to reverse these impacts, the future of many amphibians appears grim. The Sierra Nevada yellow-legged frog (Rana sierrae) is highly susceptible to Bd infection and most R. sierrae populations are extirpated following disease outbreaks. However, some populations persist and eventually recover, and frogs in these recovering populations have increased resistance against infection. Here, we conduct a 15-year reintroduction study and show that frogs collected from recovering populations and reintroduced to vacant habitats can reestablish populations despite the presence of Bd. In addition, the likelihood of establishment is influenced by site, cohort, and frog attributes. Results from viability modeling suggest that many reintroduced populations have a low probability of extinction over 50 years. These results provide a rare example of how reintroduction of resistant individuals can allow the landscape-scale recovery of disease-impacted species, and have broad implications for amphibians and other taxa that are threatened with extinction by novel pathogens.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"163 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preprocessed Monomer Interfacial Polymerization for Scalable Fabrication of High-Valent Cluster-Based Metal–Organic Framework Membranes 预处理单体界面聚合用于规模化制造高价簇基金属有机框架膜

IF 15 3区化学

ACS Combinatorial Science Pub Date : 2024-11-14 DOI: 10.1021/jacs.4c10241

Yang Feng, Zixi Kang, Zhikun Wang, Zhanning Liu, Q. Jason Niu, Weidong Fan, Lu Qiao, Jia Pang, Hu Chang, Xiaolei Cui, Lili Fan, Hailing Guo, Rongming Wang, Dan Zhao, Daofeng Sun

{"title":"Preprocessed Monomer Interfacial Polymerization for Scalable Fabrication of High-Valent Cluster-Based Metal–Organic Framework Membranes","authors":"Yang Feng, Zixi Kang, Zhikun Wang, Zhanning Liu, Q. Jason Niu, Weidong Fan, Lu Qiao, Jia Pang, Hu Chang, Xiaolei Cui, Lili Fan, Hailing Guo, Rongming Wang, Dan Zhao, Daofeng Sun","doi":"10.1021/jacs.4c10241","DOIUrl":"https://doi.org/10.1021/jacs.4c10241","url":null,"abstract":"Current research on emergent membrane materials with ordered and stable nanoporous structures often overlooks the vital facet of manufacturing scalability. We propose the preprocessed monomer interfacial polymerization (PMIP) strategy for the scalable fabrication of high-valent cluster-based metal–organic framework (MOF) membranes with robust structures. Using a roll-to-roll device on commercial polymer supports, Zr-fum-MOF membranes are continuously processed at room temperature through the PMIP approach. These large-area membranes demonstrate the preeminent hydrogen separation capabilities, boasting an order of magnitude of permeance and a thrice-enhanced selectivity when juxtaposed with conventional polymeric membranes. The obtained PMIP-Zr-fum-MOF membranes possess superior stability in water compared with interfacial polymerization (IP)-processed low-valent metal-ion-based ZIF-8 membranes. Moreover, we have implemented the PMIP strategy’s universality to process the other four diverse MOF membranes. The proposal of PMIP significantly advances the scalable fabrication of water-stable high-valent cluster MOF membranes.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"98 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diversification of molecular pattern recognition in bacterial NLR-like proteins 细菌 NLR 样蛋白分子模式识别的多样化

IF 16.6 3区化学

ACS Combinatorial Science Pub Date : 2024-11-14 DOI: 10.1038/s41467-024-54214-0

Nathalie Béchon, Nitzan Tal, Avigail Stokar-Avihail, Alon Savidor, Meital Kupervaser, Sarah Melamed, Gil Amitai, Rotem Sorek

{"title":"Diversification of molecular pattern recognition in bacterial NLR-like proteins","authors":"Nathalie Béchon, Nitzan Tal, Avigail Stokar-Avihail, Alon Savidor, Meital Kupervaser, Sarah Melamed, Gil Amitai, Rotem Sorek","doi":"10.1038/s41467-024-54214-0","DOIUrl":"https://doi.org/10.1038/s41467-024-54214-0","url":null,"abstract":"Antiviral STANDs (Avs) are bacterial anti-phage proteins evolutionarily related to immune pattern recognition receptors of the NLR family. Type 2 Avs proteins (Avs2) were suggested to recognize the phage large terminase subunit as a signature of phage infection. Here, we show that Avs2 from Klebsiella pneumoniae (KpAvs2) can recognize several different phage proteins as signature for infection. While KpAvs2 recognizes the large terminase subunit of Seuratvirus phages, we find that to protect against Dhillonvirus phages, KpAvs2 recognizes a different phage protein named KpAvs2-stimulating protein 1 (Ksap1). KpAvs2 directly binds Ksap1 to become activated, and phages mutated in Ksap1 escape KpAvs2 defense despite encoding an intact terminase. We further show that KpAvs2 protects against a third group of phages by recognizing another protein, Ksap2. Our results exemplify the evolutionary diversification of molecular pattern recognition in bacterial Avs2, and show that a single pattern recognition receptor evolved to recognize different phage-encoded proteins.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"46 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic basis of right and left ventricular heart shape 左右心室心形的遗传基础

IF 16.6 3区化学

ACS Combinatorial Science Pub Date : 2024-11-14 DOI: 10.1038/s41467-024-53594-7

Richard Burns, William J. Young, Nay Aung, Luis R. Lopes, Perry M. Elliott, Petros Syrris, Roberto Barriales-Villa, Catrin Sohrabi, Steffen E. Petersen, Julia Ramírez, Alistair Young, Patricia B. Munroe

{"title":"Genetic basis of right and left ventricular heart shape","authors":"Richard Burns, William J. Young, Nay Aung, Luis R. Lopes, Perry M. Elliott, Petros Syrris, Roberto Barriales-Villa, Catrin Sohrabi, Steffen E. Petersen, Julia Ramírez, Alistair Young, Patricia B. Munroe","doi":"10.1038/s41467-024-53594-7","DOIUrl":"https://doi.org/10.1038/s41467-024-53594-7","url":null,"abstract":"Heart shape captures variation in cardiac structure beyond traditional phenotypes of mass and volume. Although observational studies have demonstrated associations with cardiometabolic risk factors and diseases, its genetic basis is less understood. We utilised cardiovascular magnetic resonance images from 45,683 UK Biobank participants to construct a heart shape atlas from bi-ventricular end-diastolic surface mesh models through principal component (PC) analysis. Genome-wide association studies were performed on the first 11 PCs that captured 83.6% of shape variance. We identified 43 significant loci, 14 were previously unreported for cardiac traits. Genetically predicted PCs were associated with cardiometabolic diseases. In particular two PCs (2 and 3) linked with more spherical ventricles being associated with increased risk of atrial fibrillation. Our study explores the genetic basis of multidimensional bi-ventricular heart shape using PCA, reporting new loci and biology, as well as polygenic risk scores for exploring genetic relationships of heart shape with cardiometabolic diseases.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"4 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

START domains generate paralog-specific regulons from a single network architecture START 结构域从单一网络结构中产生特定于旁系亲属的调控子

IF 16.6 3区化学

ACS Combinatorial Science Pub Date : 2024-11-14 DOI: 10.1038/s41467-024-54269-z

Ashton S. Holub, Sarah G. Choudury, Ekaterina P. Andrianova, Courtney E. Dresden, Ricardo Urquidi Camacho, Igor B. Zhulin, Aman Y. Husbands

{"title":"START domains generate paralog-specific regulons from a single network architecture","authors":"Ashton S. Holub, Sarah G. Choudury, Ekaterina P. Andrianova, Courtney E. Dresden, Ricardo Urquidi Camacho, Igor B. Zhulin, Aman Y. Husbands","doi":"10.1038/s41467-024-54269-z","DOIUrl":"https://doi.org/10.1038/s41467-024-54269-z","url":null,"abstract":"Functional divergence of transcription factors (TFs) has driven cellular and organismal complexity throughout evolution, but its mechanistic drivers remain poorly understood. Here we test for new mechanisms using CORONA (CNA) and PHABULOSA (PHB), two functionally diverged paralogs in the CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) family of TFs. We show that virtually all genes bound by PHB ( ~ 99%) are also bound by CNA, ruling out occupation of distinct sets of genes as a mechanism of functional divergence. Further, genes bound and regulated by both paralogs are almost always regulated in the same direction, ruling out opposite regulation of shared targets as a mechanistic driver. Functional divergence of CNA and PHB instead results from differential usage of shared binding sites, with hundreds of uniquely regulated genes emerging from a commonly bound genetic network. Regulation of a given gene by CNA or PHB is thus a function of whether a bound site is considered ‘responsive’ versus ‘non-responsive’ by each paralog. Discrimination between responsive and non-responsive sites is controlled, at least in part, by their lipid binding START domain. This suggests a model in which HD-ZIPIII TFs use information integrated by their START domain to generate paralog-specific transcriptional outcomes from a shared network architecture. Taken together, our study identifies a mechanism of HD-ZIPIII TF paralog divergence and proposes the ubiquitously distributed START evolutionary module as a driver of functional divergence.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"35 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Co-infiltration and dynamic formation of Pd3ZnCx intermetallic carbide by syngas boosting selective hydrogenation of acetylene 通过合成气助推乙炔选择性加氢共渗和动态形成 Pd3ZnCx 金属间碳化物

IF 16.6 3区化学

ACS Combinatorial Science Pub Date : 2024-11-14 DOI: 10.1038/s41467-024-54274-2

Huan Chen, Lulu Li, Zhi-Jian Zhao, Bing Yang, Yafeng Zhang, Xiaoyan Liu, Qingqing Gu, Zhounan Yu, Xiaofeng Yang, Jinlong Gong, Aiqin Wang, Tao Zhang

{"title":"Co-infiltration and dynamic formation of Pd3ZnCx intermetallic carbide by syngas boosting selective hydrogenation of acetylene","authors":"Huan Chen, Lulu Li, Zhi-Jian Zhao, Bing Yang, Yafeng Zhang, Xiaoyan Liu, Qingqing Gu, Zhounan Yu, Xiaofeng Yang, Jinlong Gong, Aiqin Wang, Tao Zhang","doi":"10.1038/s41467-024-54274-2","DOIUrl":"https://doi.org/10.1038/s41467-024-54274-2","url":null,"abstract":"Transition metal carbide shows excellent performance in selective hydrogenation of acetylene, however, the carburization of Pd-based intermetallic compounds remains infeasible. Here we report the successful synthesis of an unprecedented Pd3ZnCx intermetallic carbide, via co-infiltration of zinc and carbon in one-step carburization by syngas. Utilizing state-of-the-art in situ characterizations and theoretical calculation, we unveil the dynamic evolution of Pd3ZnCx during carburization, forming a Pd3Zn like cubic phase carbide structure. A unique transitional state (Pdt) with low content of Zn/C co-infiltration is clearly identified facilitating phase transition and sustain incorporation of carbon and zinc at elevated temperatures. The Pd3ZnCx carbide shows by far the best catalytic performance in the selective hydrogenation of acetylene with a high selectivity (>90%) even at a high H2/C2H2 ratio. Our results therefore provide a co-infiltration strategy and dynamic insights for the one-step synthesis of Pd based intermetallic carbides, towards high-performance intermetallic compound for selective hydrogenation of acetylene.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"20 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Acceptor-Substituted N-Heterocyclic ortho-Quinodimethane: Pushing the Boundaries of Polarization in Donor–Acceptor-Substituted Polyenes 受体取代的 N-杂环邻醌二甲烷：拓展供体-受体取代多烯极化的界限

IF 15 3区化学

ACS Combinatorial Science Pub Date : 2024-11-14 DOI: 10.1021/jacs.4c13783

Jama Ariai, Urs Gellrich

{"title":"An Acceptor-Substituted N-Heterocyclic ortho-Quinodimethane: Pushing the Boundaries of Polarization in Donor–Acceptor-Substituted Polyenes","authors":"Jama Ariai, Urs Gellrich","doi":"10.1021/jacs.4c13783","DOIUrl":"https://doi.org/10.1021/jacs.4c13783","url":null,"abstract":"We report the synthesis, isolation, and characterization of a stable donor–acceptor substituted ortho-quinodimethane (oQDM). This system with an imidazolidine scaffold as the donor can also be referred to as acceptor-substituted ortho-N-heterocyclic quinodimethane (oNHQ). We have examined the extent of polarization of the conjugated π-system using single-crystal X-ray diffraction, NMR and UV/vis spectroscopy, cyclic voltammetry, and DFT computations. The bond lengths in the phenyl linker do not exhibit the alternation typical of oQDMs. In addition, the 13C and 15N NMR shifts suggest significant charge separation, an interpretation supported by the diatropic ring current determined by NICSZZ(r) computations, which is characteristic of aromatic compounds. DFT calculations show that polarization is an electronic effect that is amplified by steric influences. More strikingly, the oxidation and reduction potentials of the push–pull substituted oQDM are virtually identical to those of authenticated anionic and cationic derivatives. The results therefore indicate that an aromatic zwitterionic structure represents the electronic structure more accurately than a neutral quinoidal Lewis structure, which indicates that the acceptor-substituted oNHQ is a rare example of an organic zwitterion in which the centers of charge are in conjugation. The ambiphilic reactivity of the acceptor-substituted oNHQ, which is evidenced by the dehydrogenation of ammonia borane and the addition of phenylacetylene via heterolytic C–H bond cleavage, further supports its notation as an organic zwitterion and is reminiscent of frustrated Lewis pairs (FLPs). Thus, the acceptor-substituted oNHQ can be considered to be an intramolecular carbogenic FLP in terms of its reactivity.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"72 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Longitudinal ultra-sensitive mutation burden sequencing for precise minimal residual disease assessment in AML 纵向超灵敏突变负荷测序用于精确评估急性髓细胞性白血病的最小残留病灶

IF 16.6 3区化学

ACS Combinatorial Science Pub Date : 2024-11-14 DOI: 10.1038/s41467-024-54254-6

Yitian Wu, Shuai Zhang, Ru Feng, Kangming Xiao, Ting Wang, Jiefei Bai, Xiaoyu Zhou, Yuji Wang, Peng Dai, Hui Liu, Lucia Ruojia Wu

{"title":"Longitudinal ultra-sensitive mutation burden sequencing for precise minimal residual disease assessment in AML","authors":"Yitian Wu, Shuai Zhang, Ru Feng, Kangming Xiao, Ting Wang, Jiefei Bai, Xiaoyu Zhou, Yuji Wang, Peng Dai, Hui Liu, Lucia Ruojia Wu","doi":"10.1038/s41467-024-54254-6","DOIUrl":"https://doi.org/10.1038/s41467-024-54254-6","url":null,"abstract":"Relapse is one of the major challenges in clinical treatment of acute myeloid leukemia (AML). Though minimal residual disease (MRD) monitoring plays a crucial role in quantitative assessment of the disease, molecular MRD analysis has been mainly limited to patients diagnosed with gene fusions and NPM1 mutations. Here, we report a longitudinal ultra-sensitive mutation burden (UMB) monitoring strategy for accurate MRD analysis in AML patients regardless of genetic abnormality types. Using a Quantitative Blocker Displacement Amplification (QBDA) sequencing panel with limit of detection below 0.01% variant allele frequency (VAF), a hazard ratio of 14.8 (p < 0.001) is observed in cumulative incidence of relapse analysis of 20 patients with ≥ 2 samples during complete remission (CR). The ROC area under curve (AUC) is 0.98 when predicting relapse within 30 weeks of CR timepoint 2 (N = 20). Furthermore, we demonstrate quantitating VAF below 0.01% is essential for accurate relapse prediction.","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"313 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0