首页 > 最新文献

Cell genomics最新文献

英文 中文
NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors. NRDE2 缺乏会损害同源重组修复,并使肝癌对 PARP 抑制剂敏感。
Pub Date : 2024-05-08 Epub Date: 2024-05-01 DOI: 10.1016/j.xgen.2024.100550
Yahui Wang, Xinyi Liu, Xianbo Zuo, Cuiling Wang, Zheng Zhang, Haitao Zhang, Tao Zeng, Shunqi Chen, Mengyu Liu, Hongxia Chen, Qingfeng Song, Qi Li, Chenning Yang, Yi Le, Jinliang Xing, Hongxin Zhang, Jiaze An, Weihua Jia, Longli Kang, Hongxing Zhang, Hui Xie, Jiazhou Ye, Tianzhun Wu, Fuchu He, Xuejun Zhang, Yuanfeng Li, Gangqiao Zhou

To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10-9) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.

为了确定肝细胞癌(HCC)的新型易感基因,我们在中国人群中进行了一项罕见变异关联研究,其中包括 2,750 例病例和 4,153 例对照。我们发现了四个 HCC 相关基因,包括 NRDE2、RANBP17、RTEL1 和 STEAP3。我们以 NRDE2(指标 rs199890497 [p.N377I], p = 1.19 × 10-9)为例,证明它能促进同源重组(HR)修复并抑制 HCC。从机理上讲,NRDE2 与酪蛋白激酶 2(CK2)的亚基结合,促进了 CK2 全酶的组装和活性。NRDE2 介导的 CK2 活性增强会增加 MDC1 的磷酸化,进而促进 HR 修复。NRDE2-p.N377I变体几乎完全消除了这些功能,它使HCC细胞对多(ADP-核糖)聚合酶(PARP)抑制剂敏感,尤其是在与化疗联合使用时。总之,我们的研究结果凸显了罕见变异与 HCC 遗传易感性的相关性,这将有助于这种恶性肿瘤的精确治疗。
{"title":"NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors.","authors":"Yahui Wang, Xinyi Liu, Xianbo Zuo, Cuiling Wang, Zheng Zhang, Haitao Zhang, Tao Zeng, Shunqi Chen, Mengyu Liu, Hongxia Chen, Qingfeng Song, Qi Li, Chenning Yang, Yi Le, Jinliang Xing, Hongxin Zhang, Jiaze An, Weihua Jia, Longli Kang, Hongxing Zhang, Hui Xie, Jiazhou Ye, Tianzhun Wu, Fuchu He, Xuejun Zhang, Yuanfeng Li, Gangqiao Zhou","doi":"10.1016/j.xgen.2024.100550","DOIUrl":"10.1016/j.xgen.2024.100550","url":null,"abstract":"<p><p>To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10<sup>-9</sup>) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11099347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872393","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
Increasing equity in science requires better ethics training: A course by trainees, for trainees. 提高科学领域的公平性需要更好的伦理培训:学员为学员开设的课程。
Pub Date : 2024-05-08 Epub Date: 2024-05-01 DOI: 10.1016/j.xgen.2024.100554
Roshni A Patel, Rachel A Ungar, Alanna L Pyke, Alvina Adimoelja, Meenakshi Chakraborty, Daniel J Cotter, Malika Freund, Pagé Goddard, Justin Gomez-Stafford, Emily Greenwald, Emily Higgs, Naiomi Hunter, Tim M G MacKenzie, Anjali Narain, Tamara Gjorgjieva, Daphne O Martschenko

Despite the profound impacts of scientific research, few scientists have received the necessary training to productively discuss the ethical and societal implications of their work. To address this critical gap, we-a group of predominantly human genetics trainees-developed a course on genetics, ethics, and society. We intend for this course to serve as a template for other institutions and scientific disciplines. Our curriculum positions human genetics within its historical and societal context and encourages students to evaluate how societal norms and structures impact the conduct of scientific research. We demonstrate the utility of this course via surveys of enrolled students and provide resources and strategies for others hoping to teach a similar course. We conclude by arguing that if we are to work toward rectifying the inequities and injustices produced by our field, we must first learn to view our own research as impacting and being impacted by society.

尽管科学研究影响深远,但很少有科学家接受过必要的培训,以富有成效地讨论其工作的伦理和社会影响。为了弥补这一重大差距,我们--一群主要由人类遗传学学员组成的团队--开发了一门关于遗传学、伦理学和社会的课程。我们打算将这门课程作为其他机构和科学学科的模板。我们的课程将人类遗传学置于历史和社会背景之中,鼓励学生评估社会规范和结构如何影响科学研究的开展。我们通过对注册学生的调查证明了这门课程的实用性,并为其他希望教授类似课程的人提供了资源和策略。最后,我们认为,如果我们要努力纠正我们的领域所产生的不公平和不公正现象,我们必须首先学会将我们自己的研究视为影响社会和被社会影响的研究。
{"title":"Increasing equity in science requires better ethics training: A course by trainees, for trainees.","authors":"Roshni A Patel, Rachel A Ungar, Alanna L Pyke, Alvina Adimoelja, Meenakshi Chakraborty, Daniel J Cotter, Malika Freund, Pagé Goddard, Justin Gomez-Stafford, Emily Greenwald, Emily Higgs, Naiomi Hunter, Tim M G MacKenzie, Anjali Narain, Tamara Gjorgjieva, Daphne O Martschenko","doi":"10.1016/j.xgen.2024.100554","DOIUrl":"10.1016/j.xgen.2024.100554","url":null,"abstract":"<p><p>Despite the profound impacts of scientific research, few scientists have received the necessary training to productively discuss the ethical and societal implications of their work. To address this critical gap, we-a group of predominantly human genetics trainees-developed a course on genetics, ethics, and society. We intend for this course to serve as a template for other institutions and scientific disciplines. Our curriculum positions human genetics within its historical and societal context and encourages students to evaluate how societal norms and structures impact the conduct of scientific research. We demonstrate the utility of this course via surveys of enrolled students and provide resources and strategies for others hoping to teach a similar course. We conclude by arguing that if we are to work toward rectifying the inequities and injustices produced by our field, we must first learn to view our own research as impacting and being impacted by society.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11099339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873664","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
Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of FAIM2. 儿童肥胖症 chr12q13 位点的变异到功能分析显示,rs7132908 是 FAIM2 3' UTR 中的一个因果变异。
Pub Date : 2024-05-08 Epub Date: 2024-05-01 DOI: 10.1016/j.xgen.2024.100556
Sheridan H Littleton, Khanh B Trang, Christina M Volpe, Kieona Cook, Nicole DeBruyne, Jean Ann Maguire, Mary Ann Weidekamp, Kenyaita M Hodge, Keith Boehm, Sumei Lu, Alessandra Chesi, Jonathan P Bradfield, James A Pippin, Stewart A Anderson, Andrew D Wells, Matthew C Pahl, Struan F A Grant

The ch12q13 locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region within FAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via cis-regulation. We implicated rs7132908 as a putative causal variant by leveraging our in-house 3D genomic data and public domain datasets. Using a luciferase reporter assay, we observed allele-specific cis-regulatory activity of the immediate region harboring rs7132908. We generated isogenic human embryonic stem cell lines homozygous for either rs7132908 allele to assess changes in gene expression and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. The rs7132908 obesity risk allele influenced expression of FAIM2 and other genes and decreased the proportion of neurons produced by differentiation. We have functionally validated rs7132908 as a causal obesity variant that temporally regulates nearby effector genes and influences neurodevelopment and survival.

ch12q13位点是全基因组关联研究中发现的最重要的儿童肥胖位点之一。该位点位于 FAIM2 中的非编码区;因此,潜在的因果变异可能通过顺式调控影响疾病易感性。我们利用内部三维基因组数据和公共领域数据集,将 rs7132908 推测为一个因果变异体。通过荧光素酶报告实验,我们观察到了携带 rs7132908 的直接区域的等位基因特异性顺式调节活性。我们生成了rs7132908等位基因同源的人类胚胎干细胞系,以评估在向下丘脑神经元分化的整个过程中基因表达和染色质可及性的变化,下丘脑神经元是已知调节进食行为的关键细胞类型。rs7132908肥胖风险等位基因影响了FAIM2和其他基因的表达,并降低了分化产生的神经元比例。我们从功能上验证了 rs7132908 是肥胖症的因果变异基因,它能在时间上调节附近的效应基因,影响神经发育和存活。
{"title":"Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of FAIM2.","authors":"Sheridan H Littleton, Khanh B Trang, Christina M Volpe, Kieona Cook, Nicole DeBruyne, Jean Ann Maguire, Mary Ann Weidekamp, Kenyaita M Hodge, Keith Boehm, Sumei Lu, Alessandra Chesi, Jonathan P Bradfield, James A Pippin, Stewart A Anderson, Andrew D Wells, Matthew C Pahl, Struan F A Grant","doi":"10.1016/j.xgen.2024.100556","DOIUrl":"10.1016/j.xgen.2024.100556","url":null,"abstract":"<p><p>The ch12q13 locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region within FAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via cis-regulation. We implicated rs7132908 as a putative causal variant by leveraging our in-house 3D genomic data and public domain datasets. Using a luciferase reporter assay, we observed allele-specific cis-regulatory activity of the immediate region harboring rs7132908. We generated isogenic human embryonic stem cell lines homozygous for either rs7132908 allele to assess changes in gene expression and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. The rs7132908 obesity risk allele influenced expression of FAIM2 and other genes and decreased the proportion of neurons produced by differentiation. We have functionally validated rs7132908 as a causal obesity variant that temporally regulates nearby effector genes and influences neurodevelopment and survival.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11099382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859201","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
Unified cross-modality integration and analysis of T cell receptors and T cell transcriptomes by low-resource-aware representation learning. 通过低资源感知表征学习对 T 细胞受体和 T 细胞转录组进行统一的跨模态整合与分析。
Pub Date : 2024-05-08 Epub Date: 2024-04-29 DOI: 10.1016/j.xgen.2024.100553
Yicheng Gao, Kejing Dong, Yuli Gao, Xuan Jin, Jingya Yang, Gang Yan, Qi Liu

Single-cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq) are pivotal for investigating T cell heterogeneity. Integrating these modalities, which is expected to uncover profound insights in immunology that might otherwise go unnoticed with a single modality, faces computational challenges due to the low-resource characteristics of the multimodal data. Herein, we present UniTCR, a novel low-resource-aware multimodal representation learning framework designed for the unified cross-modality integration, enabling comprehensive T cell analysis. By designing a dual-modality contrastive learning module and a single-modality preservation module to effectively embed each modality into a common latent space, UniTCR demonstrates versatility in connecting TCR sequences with T cell transcriptomes across various tasks, including single-modality analysis, modality gap analysis, epitope-TCR binding prediction, and TCR profile cross-modality generation, in a low-resource-aware way. Extensive evaluations conducted on multiple scRNA-seq/TCR-seq paired datasets showed the superior performance of UniTCR, exhibiting the ability of exploring the complexity of immune system.

单细胞 RNA 测序(scRNA-seq)和 T 细胞受体测序(TCR-seq)是研究 T 细胞异质性的关键。由于多模态数据的低资源特性,将这些模态整合在一起面临着计算上的挑战。在此,我们提出了 UniTCR,这是一种新型的低资源感知多模态表征学习框架,旨在进行统一的跨模态整合,从而实现全面的 T 细胞分析。UniTCR 设计了双模态对比学习模块和单模态保存模块,将每种模态有效地嵌入到一个共同的潜在空间中,从而以一种低资源感知的方式在各种任务中展示了连接 TCR 序列和 T 细胞转录组的多功能性,包括单模态分析、模态差距分析、表位-TCR 结合预测和 TCR 图谱跨模态生成。在多个scRNA-seq/TCR-seq配对数据集上进行的广泛评估表明,UniTCR性能优越,具有探索免疫系统复杂性的能力。
{"title":"Unified cross-modality integration and analysis of T cell receptors and T cell transcriptomes by low-resource-aware representation learning.","authors":"Yicheng Gao, Kejing Dong, Yuli Gao, Xuan Jin, Jingya Yang, Gang Yan, Qi Liu","doi":"10.1016/j.xgen.2024.100553","DOIUrl":"10.1016/j.xgen.2024.100553","url":null,"abstract":"<p><p>Single-cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq) are pivotal for investigating T cell heterogeneity. Integrating these modalities, which is expected to uncover profound insights in immunology that might otherwise go unnoticed with a single modality, faces computational challenges due to the low-resource characteristics of the multimodal data. Herein, we present UniTCR, a novel low-resource-aware multimodal representation learning framework designed for the unified cross-modality integration, enabling comprehensive T cell analysis. By designing a dual-modality contrastive learning module and a single-modality preservation module to effectively embed each modality into a common latent space, UniTCR demonstrates versatility in connecting TCR sequences with T cell transcriptomes across various tasks, including single-modality analysis, modality gap analysis, epitope-TCR binding prediction, and TCR profile cross-modality generation, in a low-resource-aware way. Extensive evaluations conducted on multiple scRNA-seq/TCR-seq paired datasets showed the superior performance of UniTCR, exhibiting the ability of exploring the complexity of immune system.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11099349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873684","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
Regulatory barriers to US-China collaboration for generative AI development in genomic research 中美合作在基因组研究中开发生成式人工智能的监管障碍
Pub Date : 2024-05-01 DOI: 10.1016/j.xgen.2024.100564
Zhangyu Wang, Benjamin Gregg, Li Du
{"title":"Regulatory barriers to US-China collaboration for generative AI development in genomic research","authors":"Zhangyu Wang, Benjamin Gregg, Li Du","doi":"10.1016/j.xgen.2024.100564","DOIUrl":"https://doi.org/10.1016/j.xgen.2024.100564","url":null,"abstract":"","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141136769","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
MUSSEL: Enhanced Bayesian polygenic risk prediction leveraging information across multiple ancestry groups. MUSSEL:利用多个祖先群体信息的增强型贝叶斯多基因风险预测。
Pub Date : 2024-04-10 DOI: 10.1016/j.xgen.2024.100539
Jin Jin, Jianan Zhan, Jingning Zhang, Ruzhang Zhao, Jared O'Connell, Yunxuan Jiang, Steven Buyske, Christopher Gignoux, Christopher Haiman, Eimear E Kenny, Charles Kooperberg, Kari North, Bertram L Koelsch, Genevieve Wojcik, Haoyu Zhang, Nilanjan Chatterjee

Polygenic risk scores (PRSs) are now showing promising predictive performance on a wide variety of complex traits and diseases, but there exists a substantial performance gap across populations. We propose MUSSEL, a method for ancestry-specific polygenic prediction that borrows information in summary statistics from genome-wide association studies (GWASs) across multiple ancestry groups via Bayesian hierarchical modeling and ensemble learning. In our simulation studies and data analyses across four distinct studies, totaling 5.7 million participants with a substantial ancestral diversity, MUSSEL shows promising performance compared to alternatives. For example, MUSSEL has an average gain in prediction R2 across 11 continuous traits of 40.2% and 49.3% compared to PRS-CSx and CT-SLEB, respectively, in the African ancestry population. The best-performing method, however, varies by GWAS sample size, target ancestry, trait architecture, and linkage disequilibrium reference samples; thus, ultimately a combination of methods may be needed to generate the most robust PRSs across diverse populations.

目前,多基因风险评分(PRSs)在各种复杂性状和疾病方面显示出了良好的预测性能,但在不同人群之间还存在很大的性能差距。我们提出的 MUSSEL 是一种针对特定祖先的多基因预测方法,它通过贝叶斯分层建模和集合学习,从多个祖先群体的全基因组关联研究(GWAS)中借用汇总统计信息。在我们的模拟研究和四项不同研究的数据分析中,与其他替代方案相比,MUSSEL 表现出了良好的性能,这些研究的参与者总计 570 万人,其祖先具有很大的多样性。例如,在非洲血统人群中,与 PRS-CSx 和 CT-SLEB 相比,MUSSEL 在 11 个连续性状上的预测 R2 平均增益分别为 40.2% 和 49.3%。然而,表现最好的方法因 GWAS 样本大小、目标祖先、性状结构和连锁不平衡参考样本而异;因此,最终可能需要结合多种方法才能在不同人群中生成最稳健的 PRS。
{"title":"MUSSEL: Enhanced Bayesian polygenic risk prediction leveraging information across multiple ancestry groups.","authors":"Jin Jin, Jianan Zhan, Jingning Zhang, Ruzhang Zhao, Jared O'Connell, Yunxuan Jiang, Steven Buyske, Christopher Gignoux, Christopher Haiman, Eimear E Kenny, Charles Kooperberg, Kari North, Bertram L Koelsch, Genevieve Wojcik, Haoyu Zhang, Nilanjan Chatterjee","doi":"10.1016/j.xgen.2024.100539","DOIUrl":"https://doi.org/10.1016/j.xgen.2024.100539","url":null,"abstract":"<p><p>Polygenic risk scores (PRSs) are now showing promising predictive performance on a wide variety of complex traits and diseases, but there exists a substantial performance gap across populations. We propose MUSSEL, a method for ancestry-specific polygenic prediction that borrows information in summary statistics from genome-wide association studies (GWASs) across multiple ancestry groups via Bayesian hierarchical modeling and ensemble learning. In our simulation studies and data analyses across four distinct studies, totaling 5.7 million participants with a substantial ancestral diversity, MUSSEL shows promising performance compared to alternatives. For example, MUSSEL has an average gain in prediction R<sup>2</sup> across 11 continuous traits of 40.2% and 49.3% compared to PRS-CSx and CT-SLEB, respectively, in the African ancestry population. The best-performing method, however, varies by GWAS sample size, target ancestry, trait architecture, and linkage disequilibrium reference samples; thus, ultimately a combination of methods may be needed to generate the most robust PRSs across diverse populations.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874035","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
Integrative polygenic risk score improves the prediction accuracy of complex traits and diseases. 综合多基因风险评分提高了复杂性状和疾病的预测准确性。
Pub Date : 2024-04-10 Epub Date: 2024-03-19 DOI: 10.1016/j.xgen.2024.100523
Buu Truong, Leland E Hull, Yunfeng Ruan, Qin Qin Huang, Whitney Hornsby, Hilary Martin, David A van Heel, Ying Wang, Alicia R Martin, S Hong Lee, Pradeep Natarajan

Polygenic risk scores (PRSs) are an emerging tool to predict the clinical phenotypes and outcomes of individuals. We propose PRSmix, a framework that leverages the PRS corpus of a target trait to improve prediction accuracy, and PRSmix+, which incorporates genetically correlated traits to better capture the human genetic architecture for 47 and 32 diseases/traits in European and South Asian ancestries, respectively. PRSmix demonstrated a mean prediction accuracy improvement of 1.20-fold (95% confidence interval [CI], [1.10; 1.3]; p = 9.17 × 10-5) and 1.19-fold (95% CI, [1.11; 1.27]; p = 1.92 × 10-6), and PRSmix+ improved the prediction accuracy by 1.72-fold (95% CI, [1.40; 2.04]; p = 7.58 × 10-6) and 1.42-fold (95% CI, [1.25; 1.59]; p = 8.01 × 10-7) in European and South Asian ancestries, respectively. Compared to the previously cross-trait-combination methods with scores from pre-defined correlated traits, we demonstrated that our method improved prediction accuracy for coronary artery disease up to 3.27-fold (95% CI, [2.1; 4.44]; p value after false discovery rate (FDR) correction = 2.6 × 10-4). Our method provides a comprehensive framework to benchmark and leverage the combined power of PRS for maximal performance in a desired target population.

多基因风险评分(PRS)是预测个体临床表型和结果的新兴工具。我们提出了 PRSmix 和 PRSmix+,前者是一个利用目标性状的 PRS 语料库来提高预测准确性的框架,后者则纳入了遗传相关性状,以更好地捕捉欧洲和南亚血统中分别为 47 种和 32 种疾病/性状的人类遗传结构。PRSmix 的平均预测准确率提高了 1.20 倍(95% 置信区间 [CI],[1.10; 1.3];p = 9.17 × 10-5)和 1.19 倍(95% 置信区间 [CI],[1.11; 1.27];p = 1.92 × 10-6),PRSmix+则将欧洲血统和南亚血统的预测准确率分别提高了 1.72 倍(95% CI,[1.40; 2.04];p = 7.58 × 10-6)和 1.42 倍(95% CI,[1.25; 1.59];p = 8.01 × 10-7)。与之前使用预先定义的相关性状得分的交叉性状组合方法相比,我们的方法提高了冠心病的预测准确率达 3.27 倍(95% CI,[2.1; 4.44];经错误发现率 (FDR) 校正后的 p 值 = 2.6 × 10-4)。我们的方法提供了一个全面的框架,可对 PRS 的综合能力进行基准测试和利用,从而在所需的目标人群中实现最高性能。
{"title":"Integrative polygenic risk score improves the prediction accuracy of complex traits and diseases.","authors":"Buu Truong, Leland E Hull, Yunfeng Ruan, Qin Qin Huang, Whitney Hornsby, Hilary Martin, David A van Heel, Ying Wang, Alicia R Martin, S Hong Lee, Pradeep Natarajan","doi":"10.1016/j.xgen.2024.100523","DOIUrl":"10.1016/j.xgen.2024.100523","url":null,"abstract":"<p><p>Polygenic risk scores (PRSs) are an emerging tool to predict the clinical phenotypes and outcomes of individuals. We propose PRSmix, a framework that leverages the PRS corpus of a target trait to improve prediction accuracy, and PRSmix+, which incorporates genetically correlated traits to better capture the human genetic architecture for 47 and 32 diseases/traits in European and South Asian ancestries, respectively. PRSmix demonstrated a mean prediction accuracy improvement of 1.20-fold (95% confidence interval [CI], [1.10; 1.3]; p = 9.17 × 10<sup>-5</sup>) and 1.19-fold (95% CI, [1.11; 1.27]; p = 1.92 × 10<sup>-6</sup>), and PRSmix+ improved the prediction accuracy by 1.72-fold (95% CI, [1.40; 2.04]; p = 7.58 × 10<sup>-6</sup>) and 1.42-fold (95% CI, [1.25; 1.59]; p = 8.01 × 10<sup>-7</sup>) in European and South Asian ancestries, respectively. Compared to the previously cross-trait-combination methods with scores from pre-defined correlated traits, we demonstrated that our method improved prediction accuracy for coronary artery disease up to 3.27-fold (95% CI, [2.1; 4.44]; p value after false discovery rate (FDR) correction = 2.6 × 10<sup>-4</sup>). Our method provides a comprehensive framework to benchmark and leverage the combined power of PRS for maximal performance in a desired target population.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178046","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 noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children. IKZF1的非编码调控变体会增加西班牙裔/拉美裔儿童患急性淋巴细胞白血病的风险。
Pub Date : 2024-04-10 Epub Date: 2024-03-26 DOI: 10.1016/j.xgen.2024.100526
Adam J de Smith, Lara Wahlster, Soyoung Jeon, Linda Kachuri, Susan Black, Jalen Langie, Liam D Cato, Nathan Nakatsuka, Tsz-Fung Chan, Guangze Xia, Soumyaa Mazumder, Wenjian Yang, Steven Gazal, Celeste Eng, Donglei Hu, Esteban González Burchard, Elad Ziv, Catherine Metayer, Nicholas Mancuso, Jun J Yang, Xiaomei Ma, Joseph L Wiemels, Fulong Yu, Charleston W K Chiang, Vijay G Sankaran

Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval = 1.33-1.55) and a risk allele frequency of ∼18% in Hispanic/Latino populations and <0.5% in European populations. This risk allele was positively associated with Indigenous American ancestry, showed evidence of selection in human history, and was associated with reduced IKZF1 expression. We identified a putative causal variant in a downstream enhancer that is most active in pro-B cells and interacts with the IKZF1 promoter. This variant disrupts IKZF1 autoregulation at this enhancer and results in reduced enhancer activity in B cell progenitors. Our study reveals a genetic basis for the increased ALL risk in Hispanic/Latino children.

在美国,与其他种族/族裔群体相比,西班牙裔/拉美裔儿童罹患急性淋巴细胞白血病(ALL)的风险最高,但人们对这一现象的基础仍不甚了解。通过基因精细图谱分析,我们在自我报告的西班牙裔/拉美裔个体中发现了IKZF1附近的一个新的独立儿童ALL风险信号,但在非西班牙裔白人个体中却没有发现该信号,其效应大小为∼1.44(95% 置信区间 = 1.33-1.55),在西班牙裔/拉美裔人群中的风险等位基因频率为∼18%,而在非西班牙裔/拉美裔人群中的风险等位基因频率为∼20%。
{"title":"A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children.","authors":"Adam J de Smith, Lara Wahlster, Soyoung Jeon, Linda Kachuri, Susan Black, Jalen Langie, Liam D Cato, Nathan Nakatsuka, Tsz-Fung Chan, Guangze Xia, Soumyaa Mazumder, Wenjian Yang, Steven Gazal, Celeste Eng, Donglei Hu, Esteban González Burchard, Elad Ziv, Catherine Metayer, Nicholas Mancuso, Jun J Yang, Xiaomei Ma, Joseph L Wiemels, Fulong Yu, Charleston W K Chiang, Vijay G Sankaran","doi":"10.1016/j.xgen.2024.100526","DOIUrl":"10.1016/j.xgen.2024.100526","url":null,"abstract":"<p><p>Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval = 1.33-1.55) and a risk allele frequency of ∼18% in Hispanic/Latino populations and <0.5% in European populations. This risk allele was positively associated with Indigenous American ancestry, showed evidence of selection in human history, and was associated with reduced IKZF1 expression. We identified a putative causal variant in a downstream enhancer that is most active in pro-B cells and interacts with the IKZF1 promoter. This variant disrupts IKZF1 autoregulation at this enhancer and results in reduced enhancer activity in B cell progenitors. Our study reveals a genetic basis for the increased ALL risk in Hispanic/Latino children.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308158","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 revamped rat reference genome improves the discovery of genetic diversity in laboratory rats. 改进后的大鼠参考基因组提高了对实验室大鼠遗传多样性的发现。
IF 11.1 Q1 CELL BIOLOGY Pub Date : 2024-04-10 Epub Date: 2024-03-26 DOI: 10.1016/j.xgen.2024.100527
Tristan V de Jong, Yanchao Pan, Pasi Rastas, Daniel Munro, Monika Tutaj, Huda Akil, Chris Benner, Denghui Chen, Apurva S Chitre, William Chow, Vincenza Colonna, Clifton L Dalgard, Wendy M Demos, Peter A Doris, Erik Garrison, Aron M Geurts, Hakan M Gunturkun, Victor Guryev, Thibaut Hourlier, Kerstin Howe, Jun Huang, Ted Kalbfleisch, Panjun Kim, Ling Li, Spencer Mahaffey, Fergal J Martin, Pejman Mohammadi, Ayse Bilge Ozel, Oksana Polesskaya, Michal Pravenec, Pjotr Prins, Jonathan Sebat, Jennifer R Smith, Leah C Solberg Woods, Boris Tabakoff, Alan Tracey, Marcela Uliano-Silva, Flavia Villani, Hongyang Wang, Burt M Sharp, Francesca Telese, Zhihua Jiang, Laura Saba, Xusheng Wang, Terence D Murphy, Abraham A Palmer, Anne E Kwitek, Melinda R Dwinell, Robert W Williams, Jun Z Li, Hao Chen

The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.

第七次迭代的诺瓦格犬参考基因组组装--mRatBN7.2--纠正了大量错位的片段,与上一次相比,碱基水平错误减少了约 9 倍,连续性增加了 290 倍。基因注释现在更加完整,提高了基因组、转录组和蛋白质组数据集的映射精度。我们利用 mRatBN7.2 联合分析了代表 120 个实验鼠品系和亚品系的 163 个短线程全基因组测序数据集。我们定义了 2,000 万个序列变异,其中 18,700 个序列变异可能会影响 6,677 个基因的功能。我们还从 1,893 只异质种鼠中生成了新的大鼠基因图谱,并注释了转录起始位点和替代多腺苷酸化位点。mRatBN7.2 汇编以及对大鼠品系间基因组变异的广泛分析,增强了我们对大鼠基因组的了解,为研究人员进行大鼠研究提供了更多的资源。
{"title":"A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.","authors":"Tristan V de Jong, Yanchao Pan, Pasi Rastas, Daniel Munro, Monika Tutaj, Huda Akil, Chris Benner, Denghui Chen, Apurva S Chitre, William Chow, Vincenza Colonna, Clifton L Dalgard, Wendy M Demos, Peter A Doris, Erik Garrison, Aron M Geurts, Hakan M Gunturkun, Victor Guryev, Thibaut Hourlier, Kerstin Howe, Jun Huang, Ted Kalbfleisch, Panjun Kim, Ling Li, Spencer Mahaffey, Fergal J Martin, Pejman Mohammadi, Ayse Bilge Ozel, Oksana Polesskaya, Michal Pravenec, Pjotr Prins, Jonathan Sebat, Jennifer R Smith, Leah C Solberg Woods, Boris Tabakoff, Alan Tracey, Marcela Uliano-Silva, Flavia Villani, Hongyang Wang, Burt M Sharp, Francesca Telese, Zhihua Jiang, Laura Saba, Xusheng Wang, Terence D Murphy, Abraham A Palmer, Anne E Kwitek, Melinda R Dwinell, Robert W Williams, Jun Z Li, Hao Chen","doi":"10.1016/j.xgen.2024.100527","DOIUrl":"10.1016/j.xgen.2024.100527","url":null,"abstract":"<p><p>The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308159","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
Whole-genome mapping of APOBEC mutagenesis in metastatic urothelial carcinoma identifies driver hotspot mutations and a novel mutational signature. 转移性尿路上皮癌的 APOBEC 诱变全基因组图谱确定了驱动热点突变和新型突变特征。
Pub Date : 2024-04-10 Epub Date: 2024-03-28 DOI: 10.1016/j.xgen.2024.100528
J Alberto Nakauma-González, Maud Rijnders, Minouk T W Noordsij, John W M Martens, Astrid A M van der Veldt, Martijn P J Lolkema, Joost L Boormans, Harmen J G van de Werken

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) enzymes mutate specific DNA sequences and hairpin-loop structures, challenging the distinction between passenger and driver hotspot mutations. Here, we characterized 115 whole genomes of metastatic urothelial carcinoma (mUC) to identify APOBEC mutagenic hotspot drivers. APOBEC-associated mutations were detected in 92% of mUCs and were equally distributed across the genome, while APOBEC hotspot mutations (ApoHMs) were enriched in open chromatin. Hairpin loops were frequent targets of didymi (twins in Greek), two hotspot mutations characterized by the APOBEC SBS2 signature, in conjunction with an uncharacterized mutational context (Ap[C>T]). Next, we developed a statistical framework that identified ApoHMs as drivers in coding and non-coding genomic regions of mUCs. Our results and statistical framework were validated in independent cohorts of 23 non-metastatic UCs and 3,744 samples of 17 metastatic cancers, identifying cancer-type-specific drivers. Our study highlights the role of APOBEC in cancer development and may contribute to developing novel targeted therapy options for APOBEC-driven cancers.

载脂蛋白B mRNA编辑酶催化多肽样(APOBEC)酶会使特定的DNA序列和发夹环结构发生突变,这对区分乘客突变和驱动热点突变提出了挑战。在这里,我们鉴定了115个转移性尿路上皮癌(mUC)的全基因组,以确定APOBEC突变热点驱动因子。在92%的mUC中检测到了APOBEC相关突变,这些突变在整个基因组中平均分布,而APOBEC热点突变(ApoHMs)则富集在开放染色质中。发夹环是didymi(希腊语中的双胞胎)的常发目标,这两个热点突变具有APOBEC SBS2特征,同时还有一个未表征的突变背景(Ap[C>T])。接下来,我们建立了一个统计框架,以确定 ApoHMs 是 mUCs 编码和非编码基因组区域的驱动因素。我们的研究结果和统计框架在 23 个非转移性 UC 的独立队列和 17 个转移性癌症的 3,744 个样本中得到了验证,确定了癌症类型特异性驱动因子。我们的研究强调了 APOBEC 在癌症发展中的作用,并可能有助于为 APOBEC 驱动的癌症开发新的靶向治疗方案。
{"title":"Whole-genome mapping of APOBEC mutagenesis in metastatic urothelial carcinoma identifies driver hotspot mutations and a novel mutational signature.","authors":"J Alberto Nakauma-González, Maud Rijnders, Minouk T W Noordsij, John W M Martens, Astrid A M van der Veldt, Martijn P J Lolkema, Joost L Boormans, Harmen J G van de Werken","doi":"10.1016/j.xgen.2024.100528","DOIUrl":"10.1016/j.xgen.2024.100528","url":null,"abstract":"<p><p>Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) enzymes mutate specific DNA sequences and hairpin-loop structures, challenging the distinction between passenger and driver hotspot mutations. Here, we characterized 115 whole genomes of metastatic urothelial carcinoma (mUC) to identify APOBEC mutagenic hotspot drivers. APOBEC-associated mutations were detected in 92% of mUCs and were equally distributed across the genome, while APOBEC hotspot mutations (ApoHMs) were enriched in open chromatin. Hairpin loops were frequent targets of didymi (twins in Greek), two hotspot mutations characterized by the APOBEC SBS2 signature, in conjunction with an uncharacterized mutational context (Ap[C>T]). Next, we developed a statistical framework that identified ApoHMs as drivers in coding and non-coding genomic regions of mUCs. Our results and statistical framework were validated in independent cohorts of 23 non-metastatic UCs and 3,744 samples of 17 metastatic cancers, identifying cancer-type-specific drivers. Our study highlights the role of APOBEC in cancer development and may contribute to developing novel targeted therapy options for APOBEC-driven cancers.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327503","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
期刊
Cell genomics
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1