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cisDynet: An integrated platform for modeling gene-regulatory dynamics and networks cisDynet:基因调控动力学和网络建模的集成平台
Pub Date : 2023-11-23 DOI: 10.1002/imt2.152
Tao Zhu, Xinkai Zhou, Yuxin You, Lin Wang, Zhaohui He, Dijun Chen

Chromatin accessibility sequencing has been widely used for uncovering genetic regulatory mechanisms and inferring gene regulatory networks. However, effectively integrating large-scale chromatin accessibility datasets has posed a significant challenge. This is due to the lack of a comprehensive end-to-end solution, as many existing tools primarily emphasize data preprocessing and overlook downstream analyses. To bridge this gap, we have introduced cisDynet, a holistic solution that combines streamlined data preprocessing using Snakemake and R functions with advanced downstream analysis capabilities. cisDynet excels in conventional data analyses, encompassing peak statistics, peak annotation, differential analysis, motif enrichment analysis, and more. Additionally, it allows to perform sophisticated data exploration, such as tissue-specific peak identification, time course data modeling, integration of RNA-seq data to establish peak-to-gene associations, constructing regulatory networks, and conducting enrichment analysis of genome-wide association study (GWAS) variants. As a proof of concept, we applied cisDynet to reanalyze comprehensive ATAC-seq datasets across various tissues from the Encyclopedia of DNA Elements (ENCODE) project. The analysis successfully delineated tissue-specific open chromatin regions (OCRs), established connections between OCRs and target genes, and effectively linked these discoveries with 1861 GWAS variants. Furthermore, cisDynet was instrumental in dissecting the time course open chromatin data of mouse embryonic development, revealing the dynamic behavior of OCRs over developmental stages and identifying key transcription factors governing differentiation trajectories. In summary, cisDynet offers researchers a user-friendly solution that minimizes the need for extensive coding, ensures the reproducibility of results, and greatly simplifies the exploration of epigenomic data.

染色质可及性测序已广泛用于揭示基因调控机制和推断基因调控网络。然而,有效整合大规模染色质可及性数据集提出了重大挑战。这是由于缺乏全面的端到端解决方案,因为许多现有工具主要强调数据预处理而忽略了下游分析。为了弥补这一差距,我们推出了cisDynet,这是一个整体解决方案,将使用Snakemake和R函数的流线型数据预处理与先进的下游分析功能相结合。cisDynet擅长传统数据分析,包括峰统计、峰注释、差异分析、基序富集分析等。此外,它还允许执行复杂的数据探索,例如组织特异性峰识别,时间过程数据建模,RNA-seq数据集成以建立峰与基因的关联,构建调控网络,并进行全基因组关联研究(GWAS)变体的富集分析。作为概念验证,我们应用cisDynet重新分析了来自DNA元件百科全书(ENCODE)项目的各种组织的综合ATAC-seq数据集。该分析成功地描绘了组织特异性开放染色质区域(ocr),建立了ocr与靶基因之间的联系,并有效地将这些发现与1861个GWAS变体联系起来。此外,cisDynet还有助于分析小鼠胚胎发育的时间过程开放染色质数据,揭示ocr在发育阶段的动态行为,并确定控制分化轨迹的关键转录因子。总之,cisDynet为研究人员提供了一个用户友好的解决方案,最大限度地减少了对大量编码的需求,确保了结果的可重复性,并大大简化了表观基因组数据的探索。
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引用次数: 0
VeloPro: A pipeline integrating Ribo-seq and AlphaFold deciphers association patterns between translation velocity and protein structure features VeloPro:整合Ribo-seq和AlphaFold的管道,可以破译翻译速度和蛋白质结构特征之间的关联模式
Pub Date : 2023-11-19 DOI: 10.1002/imt2.148
Bian Bian, Toshitaka Kumagai, Yutaka Saito

VeloPro integrates Ribo-seq data and AlphaFold2-predicted 3D protein structure information for characterization of the association patterns between translation velocity and many protein structure features in prokaryotic and eukaryotic organisms across different taxonomical clades such as bacteria, fungi, protozoa, nematode, plants, insect, and mammals. We illustrated that association patterns between translation velocity and protein structure features differ across organisms, partially reflecting their taxonomical relationship.

VeloPro集成了核糖核酸序列数据和alphafold2预测的三维蛋白质结构信息,用于表征翻译速度与原核和真核生物中不同分类分支(如细菌、真菌、原生动物、线虫、植物、昆虫和哺乳动物)中许多蛋白质结构特征之间的关联模式。我们说明了翻译速度和蛋白质结构特征之间的关联模式在不同的生物体中是不同的,部分反映了它们的分类关系。
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引用次数: 0
Multiomics characterization and verification of clear cell renal cell carcinoma molecular subtypes to guide precise chemotherapy and immunotherapy 透明细胞肾细胞癌分子亚型的多组学表征和验证指导精确化疗和免疫治疗
Pub Date : 2023-11-16 DOI: 10.1002/imt2.147
Jialin Meng, Aimin Jiang, Xiaofan Lu, Di Gu, Qintao Ge, Suwen Bai, Yundong Zhou, Jun Zhou, Zongyao Hao, Fangrong Yan, Linhui Wang, Haitao Wang, Juan Du, Chaozhao Liang

Clear cell renal cell carcinoma (ccRCC) is a heterogeneous tumor with different genetic and molecular alterations. Schemes for ccRCC classification system based on multiomics are urgent, to promote further biological insights. Two hundred and fifty-five ccRCC patients with paired data of clinical information, transcriptome expression profiles, copy number alterations, DNA methylation, and somatic mutations were collected for identification. Bioinformatic analyses were performed based on our team's recently developed R package “MOVICS.” With 10 state-of-the-art algorithms, we identified the multiomics subtypes (MoSs) for ccRCC patients. MoS1 is an immune exhausted subtype, presented the poorest prognosis, and might be caused by an exhausted immune microenvironment, activated hypoxia features, but can benefit from PI3K/AKT inhibitors. MoS2 is an immune “cold” subtype, which represented more mutation of VHL and PBRM1, favorable prognosis, and is more suitable for sunitinib therapy. MoS3 is the immune “hot” subtype, and can benefit from the anti-PD-1 immunotherapy. We successfully verified the different molecular features of the three MoSs in external cohorts GSE22541, GSE40435, and GSE53573. Patients that received Nivolumab therapy helped us to confirm that MoS3 is suitable for anti-PD-1 therapy. E-MTAB-3267 cohort also supported the fact that MoS2 patients can respond more to sunitinib treatment. We also confirm that SETD2 is a tumor suppressor in ccRCC, along with the decreased SETD2 protein level in advanced tumor stage, and knock-down of SETD2 leads to the promotion of cell proliferation, migration, and invasion. In summary, we provide novel insights into ccRCC molecular subtypes based on robust clustering algorithms via multiomics data, and encourage future precise treatment of ccRCC patients.

透明细胞肾细胞癌(ccRCC)是一种具有不同遗传和分子改变的异质性肿瘤。基于多组学的ccRCC分类系统方案迫切需要,以促进进一步的生物学认识。收集临床信息、转录组表达谱、拷贝数改变、DNA甲基化和体细胞突变配对数据的255例ccRCC患者进行鉴定。生物信息学分析是基于最近开发的R软件包“MOVICS”进行的。通过10种最先进的算法,我们确定了ccRCC患者的多组学亚型(MoSs)。MoS1是一种免疫耗竭亚型,预后最差,可能是由耗竭的免疫微环境、激活的缺氧特征引起的,但可以从PI3K/AKT抑制剂中获益。MoS2是一种免疫“冷”亚型,VHL和PBRM1突变较多,预后良好,更适合舒尼替尼治疗。MoS3是免疫“热”亚型,可从抗pd -1免疫治疗中获益。我们成功地在外部队列GSE22541、GSE40435和GSE53573中验证了三种MoSs的不同分子特征。接受Nivolumab治疗的患者帮助我们确认了MoS3适用于抗pd -1治疗。E-MTAB-3267队列也支持这样一个事实,即MoS2患者对舒尼替尼治疗的反应更大。我们也证实了SETD2在ccRCC中是一个抑瘤因子,在肿瘤晚期,SETD2蛋白水平下降,敲低SETD2可促进细胞增殖、迁移和侵袭。总之,我们通过多组学数据提供了基于鲁棒聚类算法的ccRCC分子亚型的新见解,并鼓励未来对ccRCC患者进行精确治疗。
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引用次数: 0
Correction to “The impact of aquaculture system on the microbiome and gut metabolome of juvenile Chinese softshell turtle (Pelodiscus sinensis)” 对“养殖系统对中华软壳龟幼龟微生物组和肠道代谢组的影响”的修正
Pub Date : 2023-11-06 DOI: 10.1002/imt2.151

In Ding et al. [1], the following ethics statement should have been added.

The ethics application (No. NCULAE-20181121637) was approved by the Institutional of Animal Care and Use Committees of Nanchang University.

The authors wish to apologize for the oversight.

在Ding等[1]中,本应添加以下伦理声明。伦理申请(编号:NCULAE-20181121637)经南昌大学动物爱护利用委员会机构批准。作者希望为这一疏忽道歉。
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引用次数: 0
Correction to “MetaTrass: A high-quality metagenome assembler of the human gut microbiome by cobarcoding sequencing reads” 更正“MetaTrass:通过cobar编码测序的人类肠道微生物组的高质量宏基因组组装器”
Pub Date : 2023-11-06 DOI: 10.1002/imt2.150

In Qi et al. [1], the following ethics statement should have been added.

The ethics application (No. BGI-R052-4 and BGI-R052-4-T1) was approved by The Institutional Review Board of BGI.

The authors wish to apologize for the oversight.

在Qi等[1]中,本应添加以下伦理声明:伦理申请(编号:BGI- r052 -4和BGI- r052 -4- t1)由华大基因机构审查委员会批准。作者希望为这一疏忽道歉。
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引用次数: 0
Correction to “MetOrigin: Discriminating the origins of microbial metabolites for integrative analysis of the gut microbiome and metabolome” 更正“MetOrigin:区分微生物代谢物的来源,用于肠道微生物组和代谢物组的综合分析”
Pub Date : 2023-11-06 DOI: 10.1002/imt2.149

In Yu et al. [1], the following ethics statement should have been added.

The ethics application (No. 2021-IRB-038) was approved by the Medical Ethics Committee of Children's Hospital Affiliated to Zhejiang University School of Medicine, which was also registered in the Chinese Clinical Trial Registry (ChiCTR2100045616).

And data should have been uploaded to GSA (https://ngdc.cncb.ac.cn/gsa/).

All the sequencing data have been deposited in GSA under accession number CRA013297 (metagenome sequencing), BioProject accession number PRJCA020992.

The authors wish to apologize for the oversight.

在Yu等[1]中,本应添加以下伦理声明。伦理申请(No. 2021-IRB-038)已获浙江大学医学院附属儿童医院医学伦理委员会批准,并已在中国临床试验注册中心注册(ChiCTR2100045616)。数据应已上传到GSA (https://ngdc.cncb.ac.cn/gsa/).All),测序数据已存入GSA,登录号为CRA013297(宏基因组测序),BioProject登录号为PRJCA020992。作者希望为这一疏忽道歉。
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引用次数: 5
MIST: A microbial identification and source tracking system for next-generation sequencing data MIST:下一代测序数据的微生物鉴定和来源跟踪系统
Pub Date : 2023-11-02 DOI: 10.1002/imt2.146
Minghui Song, Chang Han, Linmeng Liu, Qiongqiong Li, Yiling Fan, Hao Gao, Dan Zhang, Yi Ren, Feng Qin, Meicheng Yang

The Professional Committee of Microbiology of the National Pharmacopoeia Commission organized the drafting of the Technical Guidelines for Microbial Whole Genome Sequencing (WGS), aiming to standardize the method process and technical indicators of microbial WGS and ensure the accuracy of sequencing and identification. On the basis of the Guidelines, we developed an integrated microbial identification and source tracking (MIST) system, which could meet the needs of microbial identification and contamination investigation in food and drug quality control. MIST integrates three analysis pipelines: 16S/18S/internal transcribed spacer amplicon-based microbial identification, WGS-based microbial identification, and single-nucleotide polymorphism-based microbial source tracking. MIST can analyze sequence data in a variety of formats, such as Fasta, base call file, and FASTQ. It can be connected to a high-throughput sequencing instrument to acquire sequencing data directly. We also developed a publicly accessible web server for MIST (http://syj.i-sanger.cn).

国家药典委员会微生物专业委员会组织编写了《微生物全基因组测序技术导则》(WGS),旨在规范微生物全基因组测序的方法流程和技术指标,保证测序鉴定的准确性。在该指南的基础上,我们开发了一套微生物鉴定和来源追踪(MIST)集成系统,可以满足食品药品质量控制中微生物鉴定和污染调查的需要。MIST集成了三个分析管道:基于16S/18S/内部转录间隔子扩增子的微生物鉴定,基于wgs的微生物鉴定和基于单核苷酸多态性的微生物来源跟踪。MIST可以分析各种格式的序列数据,例如Fasta、基本调用文件和FASTQ。可与高通量测序仪器连接,直接获取测序数据。我们还为MIST开发了一个可公开访问的web服务器(http://syj.i-sanger.cn)。
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引用次数: 0
From heart to gut: Exploring the gut microbiome in congenital heart disease 从心脏到肠道:探索先天性心脏病的肠道微生物群
Pub Date : 2023-10-30 DOI: 10.1002/imt2.144
Yuze Liu, Yuan Huang, Qiyu He, Zheng Dou, Min Zeng, Xu Wang, Shoujun Li

Congenital heart disease (CHD) is a prevalent birth defect and a significant contributor to childhood mortality. The major characteristics of CHD include cardiovascular malformations and hemodynamical disorders. However, the impact of CHD extends beyond the circulatory system. Evidence has identified dysbiosis of the gut microbiome in patients with CHD. Chronic hypoxia and inflammation associated with CHD affect the gut microbiome, leading to alterations in its number, abundance, and composition. The gut microbiome, aside from providing essential nutrients, engages in direct interactions with the host immune system and indirect interactions via metabolites. The abnormal gut microbiome or its products can translocate into the bloodstream through an impaired gut barrier, leading to an inflammatory state. Metabolites of the gut microbiome, such as short-chain fatty acids and trimethylamine N-oxide, also play important roles in the development, treatment, and prognosis of CHD. This review discusses the role of the gut microbiome in immunity, gut barrier, neurodevelopment, and perioperative period in CHD. By fostering a better understanding of the cross-talk between CHD and the gut microbiome, this review aims to contribute to improve clinical management and outcomes for CHD patients.

先天性心脏病(CHD)是一种常见的出生缺陷,也是儿童死亡率的重要因素。冠心病的主要特征包括心血管畸形和血流动力学障碍。然而,冠心病的影响超出了循环系统。有证据表明,冠心病患者存在肠道菌群失调。慢性缺氧和与冠心病相关的炎症会影响肠道微生物群,导致其数量、丰度和组成的改变。肠道微生物群除了提供必需的营养物质外,还与宿主免疫系统直接相互作用,并通过代谢物间接相互作用。异常的肠道微生物群或其产物可以通过受损的肠道屏障转移到血液中,导致炎症状态。肠道微生物组的代谢物,如短链脂肪酸和三甲胺n -氧化物,在冠心病的发生、治疗和预后中也起着重要作用。本文综述了肠道微生物群在冠心病患者的免疫、肠道屏障、神经发育和围手术期中的作用。通过更好地了解冠心病与肠道微生物群之间的相互作用,本综述旨在为改善冠心病患者的临床管理和预后做出贡献。
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引用次数: 0
Melatonin supplementation protects against traumatic colon injury by regulating SERPINA3N protein expression 补充褪黑素可通过调节SERPINA3N蛋白表达来预防外伤性结肠损伤
Pub Date : 2023-10-24 DOI: 10.1002/imt2.141
Bo Cao, Jing-Wang Gao, Qing-Peng Zhang, Xing-Ming Xu, Rui-Yang Zhao, Hang-Hang Li, Bo Wei

Traumatic colon injury (TCI) is a typical injury with high mortality. Prolongation of the intervention time window is a potentially useful approach to improving the outcomes of TCI casualties. This study aimed to identify the pathological mechanisms of TCI and to develop effective strategies to extend the survival time. A semicircular incision was made to prepare a TCI model using C57BL/6 mice. An overview of microbiota dysregulation was achieved by metagenome sequencing. Protein expression reprogramming in the intestinal epithelium was investigated using proteomics profiling. The mice that were subjected to TCI died within a short period of time when not treated. Gut symbiosis showed abrupt turbulence, and specific pathogenic bacteria rapidly proliferated. The protein expression in the intestinal epithelium was also reprogrammed. Among the differentially expressed proteins, SERPINA3N was overexpressed after TCI modeling. Deletion of Serpina3n prolonged the posttraumatic survival time of mice with TCI by improving gut homeostasis in vivo. To promote the translational application of this research, the effects of melatonin (MLT), an oral inhibitor of the SERPINA3N protein, were further investigated. MLT effectively downregulated SERPINA3N expression and mitigated TCI-induced death by suppressing the NF-κB signaling pathway. Our findings prove that preventive administration of MLT serves as an effective regimen to prolong the posttraumatic survival time by restoring gut homeostasis perturbed by TCI. It may become a novel strategy for improving the prognosis of patients suffering from TCI.

外伤性结肠损伤(TCI)是一种典型的高死亡率损伤。延长干预时间窗口是改善TCI伤亡结果的潜在有效方法。本研究旨在明确TCI的病理机制,并制定有效的策略来延长生存时间。采用C57BL/6小鼠作半圆形切口制备TCI模型。微生物群失调的概述是通过宏基因组测序实现的。利用蛋白质组学分析研究了肠上皮蛋白表达重编程。在没有治疗的情况下,接受TCI治疗的小鼠在短时间内死亡。肠道共生表现出突然的动荡,特定的致病菌迅速增殖。肠上皮蛋白表达也发生了重编程。差异表达蛋白中,TCI造模后SERPINA3N过表达。缺失Serpina3n通过改善体内肠道稳态延长TCI小鼠的创伤后存活时间。为了促进本研究的转化应用,我们进一步研究了口服SERPINA3N蛋白抑制剂褪黑素(melatonin, MLT)的作用。MLT通过抑制NF-κB信号通路,有效下调SERPINA3N表达,减轻tci诱导的死亡。我们的研究结果证明,预防性给予MLT是一种有效的方案,可以通过恢复被TCI扰乱的肠道稳态来延长创伤后生存时间。它可能成为改善TCI患者预后的新策略。
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引用次数: 0
Soil labile organic carbon fractions mediate microbial community assembly processes during long-term vegetation succession in a semiarid region 半干旱区长期植被演替过程中土壤活性有机碳组分调节微生物群落组装过程
Pub Date : 2023-10-22 DOI: 10.1002/imt2.142
Jingwei Shi, Lin Yang, Yang Liao, Jiwei Li, Shuo Jiao, Zhouping Shangguan, Lei Deng

Conceptual diagram for the labile organic carbon (OC) fractions mediating microbial assembly processes during long-term vegetation succession.

长期植被演替过程中调节微生物聚集过程的不稳定有机碳组分概念图。
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引用次数: 1
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