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Author Correction: A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data 作者更正:校正 CRISPR-Cas9 筛选数据中已确定和未知来源偏差的计算方法基准
IF 12.3 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-09-04 DOI: 10.1186/s13059-024-03387-4
Alessandro Vinceti, Rafaele M. Iannuzzi, Isabella Boyle, Lucia Trastulla, Catarina D. Campbell, Francisca Vazquez, Joshua M. Dempster, Francesco Iorio
<p><b>Correction</b><b>: </b><b>Genome Biol 25, 192 (2024)</b></p><p><b>https://doi.org/10.1186/s13059-024-03336-1</b></p><br/><p>Following publication of the original article [1], the authors identified an omission in the completing interests section. The omitted text is given in bold below.</p><p><b>Competing interests</b></p><p>FI receives funding from Open Targets, a public-private initiative involving academia and industry and performs consultancy for the joint CRUK-AstraZeneca Functional Genomics Centre and for Mosaic TX. JD is a consultant for and holds equity in Jumble Therapeutics. CDC performs consultancy for Droplet Biosciences and is a shareholder of Novartis. <b>FV receives research support from the Dependency Map Consortium, Riva Therapeutics, Bristol Myers Squibb, Merck, Illumina, and Deerfield Management. FV is on the scientific advisory board of GSK, is a consultant and holds equity in Riva Therapeutics and is a co-founder and holds equity in Jumble Therapeutics</b>. All other authors declare that they have no competing interests.</p><p>The original article [1] is corrected.</p><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Vinceti A, Iannuzzi RM, Boyle I, et al. A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data. Genome Biol. 2024;25:192. https://doi.org/10.1186/s13059-024-03336-1.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Computational Biology Research Centre, Human Technopole, Milan, Italy</p><p>Alessandro Vinceti, Rafaele M. Iannuzzi, Lucia Trastulla & Francesco Iorio</p></li><li><p>Broad Institute of Harvard and MIT, Cambridge, MA, USA</p><p>Isabella Boyle, Catarina D. Campbell, Francisca Vazquez & Joshua M. Dempster</p></li></ol><span>Authors</span><ol><li><span>Alessandro Vinceti</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Rafaele M. Iannuzzi</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Isabella Boyle</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Lucia Trastulla</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Catarina D. Campbell</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Francisca Vazquez</span>View author publications<p>You can also search for this author in <
更正:Genome Biol 25, 192 (2024)https://doi.org/10.1186/s13059-024-03336-1Following 原文[1]发表后,作者发现利益完成部分有一处遗漏。竞争利益FI接受学术界和工业界共同参与的公私合作计划 Open Targets 的资助,并为 CRUK-AstraZeneca 联合功能基因组学中心和 Mosaic TX 提供咨询服务。JD 是 Jumble Therapeutics 的顾问并持有其股份。CDC 为 Droplet Biosciences 提供顾问服务,并且是诺华公司的股东。FV 从依赖性图谱联盟(Dependency Map Consortium)、Riva Therapeutics、Bristol Myers Squibb、Merck、Illumina 和 Deerfield Management 获得研究支持。FV 是葛兰素史克公司的科学顾问委员会成员,是 Riva Therapeutics 公司的顾问并持有该公司的股份,还是 Jumble Therapeutics 公司的联合创始人并持有该公司的股份。原文[1]已更正。A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data.Genome Biol. 2024;25:192. https://doi.org/10.1186/s13059-024-03336-1.Article PubMed PubMed Central Google Scholar Download references作者和单位意大利米兰人类技术中心计算生物学研究中心Alessandro Vinceti, Rafaele M. Iannuzzi, Lucia Trastulla & Francesco Iorio美国马萨诸塞州剑桥市哈佛和麻省理工学院布罗德研究所Isabella Boyle, Catarina D. Campbell, Francisca Vazquez & Joshua M. DempsterDempsterAuthorsAlessandro VincetiView Author publications您也可以在PubMed Google Scholar中搜索该作者Rafaele M. IannuzziView Author publications您也可以在PubMed Google Scholar中搜索该作者Isabella BoyleView Author publications您也可以在PubMed Google Scholar中搜索该作者Lucia TrastullaView Author publications您也可以在PubMed Google Scholar中搜索该作者Catarina D. CampbellCampbellView author publications您也可以在PubMed Google Scholar中搜索该作者Francisca VazquezView author publications您也可以在PubMed Google Scholar中搜索该作者Joshua M. DempsterView author publications您也可以在PubMed Google Scholar中搜索该作者Francesco IorioView author publications您也可以在PubMed Google Scholar中搜索该作者Corresponding authorCorrespondence to Francesco Iorio.开放存取 本文采用知识共享署名 4.0 国际许可协议进行许可,该协议允许以任何媒介或格式使用、共享、改编、分发和复制本文,但须注明原作者和出处,提供知识共享许可协议链接,并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中,除非在材料的署名栏中另有说明。如果材料未包含在文章的知识共享许可协议中,且您打算使用的材料不符合法律规定或超出许可使用范围,则您需要直接从版权所有者处获得许可。要查看该许可的副本,请访问 http://creativecommons.org/licenses/by/4.0/。除非在数据的信用行中另有说明,否则知识共享公共领域专用免责声明 (http://creativecommons.org/publicdomain/zero/1.0/) 适用于本文提供的数据。转载与许可引用本文Vinceti, A., Iannuzzi, R.M., Boyle, I. et al. Author Correction:用于纠正 CRISPR-Cas9 筛选数据中已确定和未知来源偏差的计算方法基准。Genome Biol 25, 239 (2024). https://doi.org/10.1186/s13059-024-03387-4Download citationPublished: 04 September 2024DOI: https://doi.org/10.1186/s13059-024-03387-4Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative.
{"title":"Author Correction: A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data","authors":"Alessandro Vinceti, Rafaele M. Iannuzzi, Isabella Boyle, Lucia Trastulla, Catarina D. Campbell, Francisca Vazquez, Joshua M. Dempster, Francesco Iorio","doi":"10.1186/s13059-024-03387-4","DOIUrl":"https://doi.org/10.1186/s13059-024-03387-4","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction&lt;/b&gt;&lt;b&gt;: &lt;/b&gt;&lt;b&gt;Genome Biol 25, 192 (2024)&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;https://doi.org/10.1186/s13059-024-03336-1&lt;/b&gt;&lt;/p&gt;&lt;br/&gt;&lt;p&gt;Following publication of the original article [1], the authors identified an omission in the completing interests section. The omitted text is given in bold below.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Competing interests&lt;/b&gt;&lt;/p&gt;&lt;p&gt;FI receives funding from Open Targets, a public-private initiative involving academia and industry and performs consultancy for the joint CRUK-AstraZeneca Functional Genomics Centre and for Mosaic TX. JD is a consultant for and holds equity in Jumble Therapeutics. CDC performs consultancy for Droplet Biosciences and is a shareholder of Novartis. &lt;b&gt;FV receives research support from the Dependency Map Consortium, Riva Therapeutics, Bristol Myers Squibb, Merck, Illumina, and Deerfield Management. FV is on the scientific advisory board of GSK, is a consultant and holds equity in Riva Therapeutics and is a co-founder and holds equity in Jumble Therapeutics&lt;/b&gt;. All other authors declare that they have no competing interests.&lt;/p&gt;&lt;p&gt;The original article [1] is corrected.&lt;/p&gt;&lt;ol data-track-component=\"outbound reference\" data-track-context=\"references section\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;Vinceti A, Iannuzzi RM, Boyle I, et al. A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data. Genome Biol. 2024;25:192. https://doi.org/10.1186/s13059-024-03336-1.&lt;/p&gt;&lt;p&gt;Article PubMed PubMed Central Google Scholar &lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;p&gt;Download references&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/p&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Computational Biology Research Centre, Human Technopole, Milan, Italy&lt;/p&gt;&lt;p&gt;Alessandro Vinceti, Rafaele M. Iannuzzi, Lucia Trastulla &amp; Francesco Iorio&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Broad Institute of Harvard and MIT, Cambridge, MA, USA&lt;/p&gt;&lt;p&gt;Isabella Boyle, Catarina D. Campbell, Francisca Vazquez &amp; Joshua M. Dempster&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;span&gt;Authors&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;Alessandro Vinceti&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Rafaele M. Iannuzzi&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Isabella Boyle&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Lucia Trastulla&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Catarina D. Campbell&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Francisca Vazquez&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"150 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Improved simultaneous mapping of epigenetic features and 3D chromatin structure via ViCAR 通过 ViCAR 改进表观遗传特征和三维染色质结构的同步绘图
IF 12.3 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-09-03 DOI: 10.1186/s13059-024-03377-6
Sean M. Flynn, Somdutta Dhir, Krzysztof Herka, Colm Doyle, Larry Melidis, Angela Simeone, Winnie W. I. Hui, Rafael de Cesaris Araujo Tavares, Stefan Schoenfelder, David Tannahill, Shankar Balasubramanian
Methods to measure chromatin contacts at genomic regions bound by histone modifications or proteins are important tools to investigate chromatin organization. However, such methods do not capture the possible involvement of other epigenomic features such as G-quadruplex DNA secondary structures (G4s). To bridge this gap, we introduce ViCAR (viewpoint HiCAR), for the direct antibody-based capture of chromatin interactions at folded G4s. Through ViCAR, we showcase the first G4-3D interaction landscape. Using histone marks, we also demonstrate how ViCAR improves on earlier approaches yielding increased signal-to-noise. ViCAR is a practical and powerful tool to explore epigenetic marks and 3D genome interactomes.
测量组蛋白修饰或蛋白质结合的基因组区域染色质接触的方法是研究染色质组织的重要工具。然而,这些方法并不能捕捉到其他表观基因组特征的可能参与,如 G-四叠体 DNA 二级结构(G4s)。为了弥补这一缺陷,我们推出了 ViCAR(观点 HiCAR),用于基于抗体直接捕获折叠 G4s 上的染色质相互作用。通过 ViCAR,我们首次展示了 G4-3D 相互作用图谱。通过组蛋白标记,我们还展示了 ViCAR 如何改进早期方法,提高信噪比。ViCAR 是探索表观遗传标记和三维基因组相互作用组的实用而强大的工具。
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引用次数: 0
RNAseqCovarImpute: a multiple imputation procedure that outperforms complete case and single imputation differential expression analysis RNAseqCovarImpute:一种多重估算程序,其效果优于完整病例和单一估算差异表达分析
IF 12.3 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-09-03 DOI: 10.1186/s13059-024-03376-7
Brennan H. Baker, Sheela Sathyanarayana, Adam A. Szpiro, James W. MacDonald, Alison G. Paquette
Missing covariate data is a common problem that has not been addressed in observational studies of gene expression. Here, we present a multiple imputation method that accommodates high dimensional gene expression data by incorporating principal component analysis of the transcriptome into the multiple imputation prediction models to avoid bias. Simulation studies using three datasets show that this method outperforms complete case and single imputation analyses at uncovering true positive differentially expressed genes, limiting false discovery rates, and minimizing bias. This method is easily implemented via an R Bioconductor package, RNAseqCovarImpute that integrates with the limma-voom pipeline for differential expression analysis.
协变量数据缺失是基因表达观测研究中尚未解决的一个常见问题。在这里,我们提出了一种多重估算方法,通过将转录组的主成分分析纳入多重估算预测模型来避免偏差,从而适应高维基因表达数据。使用三个数据集进行的模拟研究表明,该方法在发现真正的阳性差异表达基因、限制误发现率和最小化偏倚方面优于完全情况分析和单一归因分析。这种方法可通过 R Bioconductor 软件包 RNAseqCovarImpute 轻松实现,该软件包可与 limma-voom 差异表达分析管道集成。
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引用次数: 0
Enhlink infers distal and context-specific enhancer–promoter linkages Enhlink推断远端和特定语境的增强子-启动子连接
IF 12.3 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-09-02 DOI: 10.1186/s13059-024-03374-9
Olivier B. Poirion, Wulin Zuo, Catrina Spruce, Candice N. Baker, Sandra L. Daigle, Ashley Olson, Daniel A. Skelly, Elissa J. Chesler, Christopher L. Baker, Brian S. White
Enhlink is a computational tool for scATAC-seq data analysis, facilitating precise interrogation of enhancer function at the single-cell level. It employs an ensemble approach incorporating technical and biological covariates to infer condition-specific regulatory DNA linkages. Enhlink can integrate multi-omic data for enhanced specificity, when available. Evaluation with simulated and real data, including multi-omic datasets from the mouse striatum and novel promoter capture Hi-C data, demonstrate that Enhlink outperfoms alternative methods. Coupled with eQTL analysis, it identified a putative super-enhancer in striatal neurons. Overall, Enhlink offers accuracy, power, and potential for revealing novel biological insights in gene regulation.
Enhlink 是一种用于 scATAC-seq 数据分析的计算工具,有助于在单细胞水平上精确检测增强子的功能。它采用一种包含技术和生物协变量的集合方法来推断特定条件下的 DNA 连接调控。如果有多组数据,Enhlink 还能整合多组数据,以提高特异性。利用模拟数据和真实数据(包括来自小鼠纹状体的多组数据集和新型启动子捕获 Hi-C 数据)进行的评估表明,Enhlink 优于其他方法。结合 eQTL 分析,它在纹状体神经元中发现了一个潜在的超级增强子。总之,Enhlink 在揭示基因调控的新生物学见解方面具有准确性、强大的功能和潜力。
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引用次数: 0
Dissecting the genetic basis of UV-B responsive metabolites in rice 剖析水稻紫外线-B 反应性代谢物的遗传基础
IF 12.3 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-08-29 DOI: 10.1186/s13059-024-03372-x
Feng Zhang, Chenkun Yang, Hao Guo, Yufei Li, Shuangqian Shen, Qianqian Zhou, Chun Li, Chao Wang, Ting Zhai, Lianghuan Qu, Cheng Zhang, Xianqing Liu, Jie Luo, Wei Chen, Shouchuang Wang, Jun Yang, Cui Yu, Yanyan Liu
UV-B, an important environmental factor, has been shown to affect the yield and quality of rice (Oryza sativa) worldwide. However, the molecular mechanisms underlying the response to UV-B stress remain elusive in rice. We perform comprehensive metabolic profiling of leaves from 160 diverse rice accessions under UV-B and normal light conditions using a widely targeted metabolomics approach. Our results reveal substantial differences in metabolite accumulation between the two major rice subspecies indica and japonica, especially after UV-B treatment, implying the possible role and mechanism of metabolome changes in subspecies differentiation and the stress response. We next conduct a transcriptome analysis from four representative rice varieties under UV-B stress, revealing genes from amino acid and flavonoid pathways involved in the UV-B response. We further perform a metabolite-based genome-wide association study (mGWAS), which reveals 3307 distinct loci under UV-B stress. Identification and functional validation of candidate genes show that OsMYB44 regulates tryptamine accumulation to mediate UV-B tolerance, while OsUVR8 interacts with OsMYB110 to promote flavonoid accumulation and UV-B tolerance in a coordinated manner. Additionally, haplotype analysis suggests that natural variation of OsUVR8groupA contributes to UV-B resistance in rice. Our study reveals the complex biochemical and genetic foundations that govern the metabolite dynamics underlying the response, tolerance, and adaptive strategies of rice to UV-B stress. These findings provide new insights into the biochemical and genetic basis of the metabolome underlying the crop response, tolerance, and adaptation to UV-B stress.
紫外线-B 作为一种重要的环境因素,已被证明会影响全球水稻(Oryza sativa)的产量和品质。然而,水稻对紫外线-B 胁迫反应的分子机制仍然难以捉摸。我们采用广泛的靶向代谢组学方法,对紫外线-B 和正常光照条件下 160 种不同水稻品种的叶片进行了全面的代谢分析。我们的研究结果表明,籼稻和粳稻这两个主要水稻亚种之间的代谢物积累存在很大差异,尤其是在紫外线-B 处理之后,这意味着代谢组的变化在亚种分化和胁迫响应中可能扮演的角色和机制。接下来,我们对紫外线-B 胁迫下的四个代表性水稻品种进行了转录组分析,揭示了参与紫外线-B 胁迫响应的氨基酸和类黄酮通路基因。我们进一步进行了基于代谢物的全基因组关联研究(mGWAS),发现了紫外线-B 胁迫下的 3307 个不同基因位点。候选基因的鉴定和功能验证表明,OsMYB44调控色胺积累以介导紫外线-B耐受性,而OsUVR8与OsMYB110相互作用,以协调的方式促进类黄酮积累和紫外线-B耐受性。此外,单倍型分析表明,OsUVR8groupA 的自然变异有助于水稻的抗紫外线-B 能力。我们的研究揭示了影响水稻对紫外线-B 胁迫的响应、耐受性和适应策略的代谢动态的复杂生化和遗传基础。这些发现为作物对紫外线-B 胁迫的响应、耐受和适应所依赖的代谢组的生化和遗传基础提供了新的见解。
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引用次数: 0
NERD-seq: a novel approach of Nanopore direct RNA sequencing that expands representation of non-coding RNAs NERD-seq:纳米孔直接 RNA 测序的新方法,可扩展非编码 RNA 的代表性
IF 12.3 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-08-28 DOI: 10.1186/s13059-024-03375-8
Luke Saville, Li Wu, Jemaneh Habtewold, Yubo Cheng, Babita Gollen, Liam Mitchell, Matthew Stuart-Edwards, Travis Haight, Majid Mohajerani, Athanasios Zovoilis
Non-coding RNAs (ncRNAs) are frequently documented RNA modification substrates. Nanopore Technologies enables the direct sequencing of RNAs and the detection of modified nucleobases. Ordinarily, direct RNA sequencing uses polyadenylation selection, studying primarily mRNA gene expression. Here, we present NERD-seq, which enables detection of multiple non-coding RNAs, excluded by the standard approach, alongside natively polyadenylated transcripts. Using neural tissues as a proof of principle, we show that NERD-seq expands representation of frequently modified non-coding RNAs, such as snoRNAs, snRNAs, scRNAs, srpRNAs, tRNAs, and rRFs. NERD-seq represents an RNA-seq approach to simultaneously study mRNA and ncRNA epitranscriptomes in brain tissues and beyond.
非编码 RNA(ncRNA)是经常被记录的 RNA 修饰底物。纳米孔技术可对 RNA 进行直接测序,并检测修饰的核碱基。通常,直接 RNA 测序使用多聚腺苷酸选择,主要研究 mRNA 基因表达。在这里,我们介绍 NERD-seq,它能检测标准方法排除的多种非编码 RNA,以及原生多聚腺苷酸转录本。以神经组织为原理验证,我们发现 NERD-seq 扩展了经常修饰的非编码 RNAs 的代表性,如 snoRNAs、snRNAs、scRNAs、srpRNAs、tRNAs 和 rRFs。NERD-seq代表了一种RNA-seq方法,可同时研究脑组织及其他组织中的mRNA和ncRNA表转录组。
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引用次数: 0
Gut microbiota contributes to high-altitude hypoxia acclimatization of human populations 肠道微生物群有助于人类适应高海拔缺氧环境
IF 12.3 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-08-28 DOI: 10.1186/s13059-024-03373-w
Qian Su, Dao-Hua Zhuang, Yu-Chun Li, Yu Chen, Xia-Yan Wang, Ming-Xia Ge, Ting-Yue Xue, Qi-Yuan Zhang, Xin-Yuan Liu, Fan-Qian Yin, Yi-Ming Han, Zong-Liang Gao, Long Zhao, Yong-Xuan Li, Meng-Jiao Lv, Li-Qin Yang, Tian-Rui Xia, Yong-Jun Luo, Zhigang Zhang, Qing-Peng Kong
The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in the microbiota under such conditions and the existence of any dominant or core bacteria that may assist in host acclimatization. To address these issues, and to control for variables commonly present in previous studies which significantly impact the results obtained, namely genetic background, ethnicity, lifestyle, and diet, we conducted a 108-day longitudinal study on the same cohort comprising 45 healthy Han adults who traveled from lowland Chongqing, 243 masl, to high-altitude plateau Lhasa, Xizang, 3658 masl, and back. Using shotgun metagenomic profiling, we study temporal changes in gut microbiota composition at different timepoints. The results show a significant reduction in the species and functional diversity of the gut microbiota, along with a marked increase in functional redundancy. These changes are primarily driven by the overgrowth of Blautia A, a genus that is also abundant in six independent Han cohorts with long-term duration in lower hypoxia environment in Shigatse, Xizang, at 4700 masl. Further animal experiments indicate that Blautia A-fed mice exhibit enhanced intestinal health and a better acclimatization phenotype to sustained hypoxic stress. Our study underscores the importance of Blautia A species in the gut microbiota’s rapid response to high-altitude hypoxia and its potential role in maintaining intestinal health and aiding host adaptation to extreme environments, likely via anti-inflammation and intestinal barrier protection.
人类肠道微生物群与高海拔缺氧适应之间的关系仍然存在很大争议。这主要是由于在这种条件下微生物群可能发生的时间性变化以及是否存在可能帮助宿主适应环境的优势菌或核心菌还存在不确定性。为了解决这些问题,并控制以往研究中常见的对结果有重大影响的变量,即遗传背景、种族、生活方式和饮食,我们对同一队列中的 45 名健康汉族成年人进行了 108 天的纵向研究,他们从海拔 243 米的低地重庆前往海拔 3658 米的高海拔高原拉萨、西藏和返回。我们利用霰弹枪元基因组剖析技术研究了不同时间点肠道微生物群组成的时间变化。结果显示,肠道微生物群的物种和功能多样性显著减少,功能冗余明显增加。这些变化主要是由 Blautia A 过度生长引起的,在西藏日喀则海拔 4700 米的低氧环境中长期生活的六个独立汉族队列中,Blautia A 的数量也很丰富。进一步的动物实验表明,饲喂 Blautia A 的小鼠在持续的缺氧压力下表现出更强的肠道健康和更好的适应表型。我们的研究强调了 Blautia A 物种在肠道微生物群对高海拔缺氧的快速反应中的重要性,以及它在维持肠道健康和帮助宿主适应极端环境中的潜在作用,这可能是通过抗炎和肠道屏障保护实现的。
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引用次数: 0
Contribution of homoeologous exchange to domestication of polyploid Brassica. 同源交换对多倍体芸薹属植物驯化的贡献。
IF 10.1 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-08-27 DOI: 10.1186/s13059-024-03370-z
Tianpeng Wang, Aalt D J van Dijk, Ranze Zhao, Guusje Bonnema, Xiaowu Wang

Background: Polyploidy is widely recognized as a significant evolutionary force in the plant kingdom, contributing to the diversification of plants. One of the notable features of allopolyploidy is the occurrence of homoeologous exchange (HE) events between the subgenomes, causing changes in genomic composition, gene expression, and phenotypic variations. However, the role of HE in plant adaptation and domestication remains unclear.

Results: Here we analyze the whole-genome resequencing data from Brassica napus accessions representing the different morphotypes and ecotypes, to investigate the role of HE in domestication. Our findings demonstrate frequent occurrence of HEs in Brassica napus, with substantial HE patterns shared across populations, indicating their potential role in promoting crop domestication. HE events are asymmetric, with the A genome more frequently replacing C genome segments. These events show a preference for specific genomic regions and vary among populations. We also identify candidate genes in HE regions specific to certain populations, which likely contribute to flowering-time diversification across diverse morphotypes and ecotypes. In addition, we assemble a new genome of a swede accession, confirming the HE signals on the genome and their potential involvement in root tuber development. By analyzing HE in another allopolyploid species, Brassica juncea, we characterize a potential broader role of HE in allopolyploid crop domestication.

Conclusions: Our results provide novel insights into the domestication of polyploid Brassica species and highlight homoeologous exchange as a crucial mechanism for generating variations that are selected for crop improvement in polyploid species.

背景:多倍体被广泛认为是植物界的重要进化力量,有助于植物的多样化。异源多倍体的一个显著特点是亚基因组之间发生同源交换(HE)事件,导致基因组组成、基因表达和表型变异发生变化。然而,HE 在植物适应和驯化中的作用仍不清楚:在此,我们分析了代表不同形态和生态型的甘蓝型油菜的全基因组重测序数据,以研究 HE 在驯化过程中的作用。我们的研究结果表明,HEs 在甘蓝型油菜中频繁出现,不同种群之间共享大量的 HE 模式,这表明 HEs 在促进作物驯化中的潜在作用。HE 事件是不对称的,A 基因组更频繁地取代 C 基因组片段。这些事件显示出对特定基因组区域的偏好,并且在不同种群之间存在差异。我们还在 HE 区域发现了某些种群特有的候选基因,这些基因可能有助于不同形态和生态型的花期多样化。此外,我们还组装了一个獐子属植物的新基因组,确认了基因组上的 HE 信号及其在块根发育中的潜在参与。通过分析另一个异源多倍体物种甘蓝的HE,我们描述了HE在异源多倍体作物驯化中可能发挥的更广泛作用:我们的研究结果为多倍体芸苔属物种的驯化提供了新的视角,并强调了同源交换是多倍体物种中产生变异的关键机制,这些变异被选作作物改良的原料。
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引用次数: 0
Real-time identification of epistatic interactions in SARS-CoV-2 from large genome collections 从大型基因组集合中实时识别 SARS-CoV-2 中的表观相互作用
IF 12.3 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-08-22 DOI: 10.1186/s13059-024-03355-y
Gabriel Innocenti, Maureen Obara, Bibiana Costa, Henning Jacobsen, Maeva Katzmarzyk, Luka Cicin-Sain, Ulrich Kalinke, Marco Galardini
The emergence of the SARS-CoV-2 virus has highlighted the importance of genomic epidemiology in understanding the evolution of pathogens and guiding public health interventions. The Omicron variant in particular has underscored the role of epistasis in the evolution of lineages with both higher infectivity and immune escape, and therefore the necessity to update surveillance pipelines to detect them early on. In this study, we apply a method based on mutual information between positions in a multiple sequence alignment, which is capable of scaling up to millions of samples. We show how it can reliably predict known experimentally validated epistatic interactions, even when using as little as 10,000 sequences, which opens the possibility of making it a near real-time prediction system. We test this possibility by modifying the method to account for the sample collection date and apply it retrospectively to multiple sequence alignments for each month between March 2020 and March 2023. We detected a cornerstone epistatic interaction in the Spike protein between codons 498 and 501 as soon as seven samples with a double mutation were present in the dataset, thus demonstrating the method’s sensitivity. We test the ability of the method to make inferences about emerging interactions by testing candidates predicted after March 2023, which we validate experimentally. We show how known epistatic interaction in SARS-CoV-2 can be detected with high sensitivity, and how emerging ones can be quickly prioritized for experimental validation, an approach that could be implemented downstream of pandemic genome sequencing efforts.
SARS-CoV-2 病毒的出现凸显了基因组流行病学在了解病原体进化和指导公共卫生干预方面的重要性。尤其是 Omicron 变异突显了外显子在具有较高感染性和免疫逃逸性的品系进化中的作用,因此有必要更新监测管道以尽早发现它们。在本研究中,我们采用了一种基于多序列比对中位置间互信息的方法,该方法可扩展至数百万个样本。我们展示了该方法如何可靠地预测已知的、经实验验证的表观相互作用,即使使用的序列少至 10,000 个,这为使其成为近乎实时的预测系统提供了可能性。我们通过修改该方法以考虑样本采集日期,并将其追溯应用于 2020 年 3 月至 2023 年 3 月期间每个月的多序列比对,来测试这种可能性。只要数据集中出现 7 个双突变样本,我们就能检测到 Spike 蛋白质中密码子 498 和 501 之间的基石表观相互作用,从而证明了该方法的灵敏度。我们测试了 2023 年 3 月之后预测的候选相互作用,并通过实验验证了该方法推断新出现相互作用的能力。我们展示了如何高灵敏度地检测 SARS-CoV-2 中已知的表观相互作用,以及如何快速优先对新出现的相互作用进行实验验证,这种方法可以在大流行病基因组测序工作的下游实施。
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引用次数: 0
Current limitations in predicting mRNA translation with deep learning models. 目前利用深度学习模型预测 mRNA 翻译的局限性。
IF 10.1 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-08-20 DOI: 10.1186/s13059-024-03369-6
Niels Schlusser, Asier González, Muskan Pandey, Mihaela Zavolan

Background: The design of nucleotide sequences with defined properties is a long-standing problem in bioengineering. An important application is protein expression, be it in the context of research or the production of mRNA vaccines. The rate of protein synthesis depends on the 5' untranslated region (5'UTR) of the mRNAs, and recently, deep learning models were proposed to predict the translation output of mRNAs from the 5'UTR sequence. At the same time, large data sets of endogenous and reporter mRNA translation have become available.

Results: In this study, we use complementary data obtained in two different cell types to assess the accuracy and generality of currently available models for predicting translational output. We find that while performing well on the data sets on which they were trained, deep learning models do not generalize well to other data sets, in particular of endogenous mRNAs, which differ in many properties from reporter constructs.

Conclusions: These differences limit the ability of deep learning models to uncover mechanisms of translation control and to predict the impact of genetic variation. We suggest directions that combine high-throughput measurements and machine learning to unravel mechanisms of translation control and improve construct design.

背景:设计具有明确特性的核苷酸序列是生物工程中一个长期存在的问题。蛋白质表达是一个重要的应用领域,无论是研究还是生产 mRNA 疫苗都是如此。蛋白质的合成速度取决于 mRNA 的 5' 非翻译区(5'UTR),最近有人提出了深度学习模型,从 5'UTR 序列预测 mRNA 的翻译输出。与此同时,内源性和报告基因 mRNA 翻译的大型数据集也已可用:在这项研究中,我们利用在两种不同细胞类型中获得的互补数据来评估目前可用的翻译输出预测模型的准确性和通用性。我们发现,虽然深度学习模型在其所训练的数据集上表现良好,但并不能很好地泛化到其他数据集上,特别是内源性 mRNA,它们与报告构建体在许多特性上存在差异:这些差异限制了深度学习模型揭示翻译控制机制和预测遗传变异影响的能力。我们建议将高通量测量与机器学习相结合,以揭示翻译控制机制并改进构建物设计。
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Genome Biology
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