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Mycobacterial metabolic model development for drug target identification. 用于药物靶点鉴定的分枝杆菌代谢模型开发。
Pub Date : 2023-04-30 eCollection Date: 2023-01-01 DOI: 10.46471/gigabyte.80
Bridget P Bannerman, Alexandru Oarga, Jorge Júlvez

Antibiotic resistance is increasing at an alarming rate, and three related mycobacteria are sources of widespread infections in humans. According to the World Health Organization, Mycobacterium leprae, which causes leprosy, is still endemic in tropical countries; Mycobacterium tuberculosis is the second leading infectious killer worldwide after COVID-19; and Mycobacteroides abscessus, a group of non-tuberculous mycobacteria, causes lung infections and other healthcare-associated infections in humans. Due to the rise in resistance to common antibacterial drugs, it is critical that we develop alternatives to traditional treatment procedures. Furthermore, an understanding of the biochemical mechanisms underlying pathogenic evolution is important for the treatment and management of these diseases. In this study, metabolic models have been developed for two bacterial pathogens, M. leprae and My. abscessus, and a new computational tool has been used to identify potential drug targets, which are referred to as bottleneck reactions. The genes, reactions, and pathways in each of these organisms have been highlighted; the potential drug targets can be further explored as broad-spectrum antibacterials and the unique drug targets for each pathogen are significant for precision medicine initiatives. The models and associated datasets described in this paper are available in GigaDB, Biomodels, and PatMeDB repositories.

抗生素耐药性正在以惊人的速度增加,而三种相关的分枝杆菌是人类广泛感染的来源。根据世界卫生组织的资料,导致麻风病的麻风分枝杆菌仍在热带国家流行;结核分枝杆菌是仅次于 COVID-19 的全球第二大传染病杀手;脓肿分枝杆菌是一类非结核分枝杆菌,可导致肺部感染和其他与医疗相关的人类感染。由于常见抗菌药物的抗药性不断增加,我们必须开发传统治疗方法的替代品。此外,了解病原体演变的生化机制对于治疗和管理这些疾病也非常重要。在这项研究中,我们为两种细菌病原体--麻风杆菌和脓肿霉菌--建立了代谢模型,并使用一种新的计算工具来确定潜在的药物靶点,这些靶点被称为瓶颈反应。这些生物体中的基因、反应和途径都得到了强调;潜在的药物靶点可作为广谱抗菌药物进一步开发,而每种病原体的独特药物靶点对精准医疗计划具有重要意义。本文所述模型和相关数据集可在 GigaDB、Biomodels 和 PatMeDB 资源库中查阅。
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引用次数: 0
The first genome assembly of the amphibian nematode parasite (Aplectana chamaeleonis). 两栖动物线虫寄生虫(Aplectana chamaeleonis)的首次基因组组装。
Pub Date : 2023-03-27 eCollection Date: 2023-01-01 DOI: 10.46471/gigabyte.79
Lei Han, Tianlu Liu, Fengping He, Zhijun Hou

Cosmocercoid nematodes are common parasites of the digestive tract of amphibians. Genomic resources are important for understanding the evolution of a species and the molecular mechanisms of parasite adaptation. So far, no genome resource of Cosmocercoid has been reported. In 2020, a massive Cosmocercoid infection was found in the small intestine of a toad, causing severe intestinal blockage. We morphologically identified this parasite as A. chamaeleonis. Here, we report the first A. chamaeleonis genome with a genome size of 1.04 Gb. The repeat content of this A. chamaeleonis genome is 72.45%, and the total length is 751 Mb. This resource is fundamental for understanding the evolution of Cosmocercoid and provides the molecular basis for Cosmocercoid infection and control.

Cosmocercoid 线虫是两栖动物消化道的常见寄生虫。基因组资源对于了解一个物种的进化和寄生虫适应的分子机制非常重要。迄今为止,还没有关于 Cosmocercoid 的基因组资源的报道。2020 年,在一只蟾蜍的小肠中发现了大量的 Cosmocercoid 感染,造成了严重的肠道堵塞。我们从形态学上确定这种寄生虫为 A. chamaeleonis。在此,我们报告了第一个 A. chamaeleonis 基因组,其基因组大小为 1.04 Gb。该 A. chamaeleonis 基因组的重复率为 72.45%,总长度为 751 Mb。这一资源对于了解 Cosmocercoid 的进化至关重要,并为 Cosmocercoid 的感染和控制提供了分子基础。
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引用次数: 0
Genome assembly of the deep-sea coral Lophelia pertusa. 深海珊瑚 Lophelia pertusa 的基因组组装。
Pub Date : 2023-03-16 eCollection Date: 2023-01-01 DOI: 10.46471/gigabyte.78
Santiago Herrera, Erik E Cordes

Like their shallow-water counterparts, cold-water corals create reefs that support highly diverse communities, and these structures are subject to numerous anthropogenic threats. Here, we present the genome assembly of Lophelia pertusa from the southeastern coast of the USA, the first one for a deep-sea scleractinian coral species. We generated PacBio continuous long reads data for an initial assembly and proximity ligation data for scaffolding. The assembly was annotated using evidence from transcripts, proteins, and ab initio gene model predictions. This assembly is comparable to high-quality reference genomes from shallow-water scleractinian corals. The assembly comprises 2,858 scaffolds (N50 1.6 Mbp) and has a size of 556.9 Mbp. Approximately 57% of the genome comprises repetitive elements and 34% of coding DNA. We predicted 41,089 genes, including 91.1% of complete metazoan orthologs. This assembly will facilitate investigations into the ecology of this species and the evolution of deep-sea corals.

与浅水珊瑚一样,冷水珊瑚形成的珊瑚礁支持着高度多样化的群落,而这些结构却受到许多人为因素的威胁。在这里,我们展示了来自美国东南海岸的 Lophelia pertusa 的基因组组装结果,这是首个深海硬骨珊瑚物种的基因组组装结果。我们生成了用于初步组装的 PacBio 连续长读数数据和用于搭建脚手架的近距离连接数据。我们利用来自转录本、蛋白质和 ab initio 基因模型预测的证据对组装结果进行了注释。该组装结果可与浅水硬骨珊瑚的高质量参考基因组相媲美。该基因组包括 2,858 个支架(N50 1.6 Mbp),大小为 556.9 Mbp。约 57% 的基因组由重复元件组成,34% 的基因组由编码 DNA 组成。我们预测了 41,089 个基因,其中包括 91.1% 的完整元古动物直向同源物。该基因组的组装将有助于研究该物种的生态学和深海珊瑚的进化。
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引用次数: 0
PhysiCOOL: A generalized framework for model Calibration and Optimization Of modeLing projects. PhysiCOOL:用于模型校准和优化模式化项目的通用框架。
Pub Date : 2023-02-28 eCollection Date: 2023-01-01 DOI: 10.46471/gigabyte.77
Inês G Gonçalves, David A Hormuth, Sandhya Prabhakaran, Caleb M Phillips, José Manuel García-Aznar

In silico models of biological systems are usually very complex and rely on a large number of parameters describing physical and biological properties that require validation. As such, parameter space exploration is an essential component of computational model development to fully characterize and validate simulation results. Experimental data may also be used to constrain parameter space (or enable model calibration) to enhance the biological relevance of model parameters. One widely used computational platform in the mathematical biology community is PhysiCell, which provides a standardized approach to agent-based models of biological phenomena at different time and spatial scales. Nonetheless, one limitation of PhysiCell is the lack of a generalized approach for parameter space exploration and calibration that can be run without high-performance computing access. Here, we present PhysiCOOL, an open-source Python library tailored to create standardized calibration and optimization routines for PhysiCell models.

生物系统的硅学模型通常非常复杂,依赖于大量需要验证的物理和生物特性参数。因此,参数空间探索是计算模型开发的重要组成部分,可全面描述和验证模拟结果。实验数据也可用于限制参数空间(或进行模型校准),以提高模型参数的生物相关性。数学生物学界广泛使用的一个计算平台是 PhysiCell,它为不同时间和空间尺度的生物现象提供了基于代理模型的标准化方法。然而,PhysiCell 的一个局限是缺乏一种无需高性能计算接入即可运行的参数空间探索和校准通用方法。在这里,我们介绍 PhysiCOOL,这是一个开源 Python 库,专门用于为 PhysiCell 模型创建标准化的校准和优化例程。
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引用次数: 0
Improvements to the Gulf pipefish Syngnathus scovelli genome. 对墨西哥湾河豚Syngnathus scovelli基因组的改进。
Pub Date : 2023-02-20 eCollection Date: 2023-01-01 DOI: 10.46471/gigabyte.76
Balan Ramesh, Clay M Small, Hope Healey, Bernadette Johnson, Elyse Barker, Mark Currey, Susan Bassham, Megean Myers, William A Cresko, Adam Gregory Jones

The Gulf pipefish Syngnathus scovelli has emerged as an important species for studying sexual selection, development, and physiology. Comparative evolutionary genomics research involving fishes from Syngnathidae depends on having a high-quality genome assembly and annotation. However, the first S. scovelli genome assembled using short-read sequences and a smaller RNA-sequence dataset has limited contiguity and a relatively poor annotation. Here, using PacBio long-read high-fidelity sequences and a proximity ligation library, we generate an improved assembly to obtain 22 chromosome-level scaffolds. Compared to the first assembly, the gaps in the improved assembly are smaller, the N75 is larger, and our genome is ~95% BUSCO complete. Using a large body of RNA-Seq reads from different tissue types and NCBI's Eukaryotic Annotation Pipeline, we discovered 28,162 genes, of which 8,061 are non-coding genes. Our new genome assembly and annotation are tagged as a RefSeq genome by NCBI and provide enhanced resources for research work involving S. scovelli..

墨西哥湾管鱼Syngnathus scovelli已成为研究性选择、发育和生理学的重要物种。涉及Syngnathidae鱼类的比较进化基因组学研究依赖于高质量的基因组组装和注释。然而,使用短读序列和较小的RNA序列数据集组装的第一个S.scovelli基因组具有有限的邻接性和相对较差的注释。在这里,使用PacBio长读高保真序列和邻近连接文库,我们生成了一个改进的组装,以获得22个染色体水平的支架。与第一次组装相比,改进后的组装中的间隙更小,N75更大,我们的基因组完成了约95%的BUSCO。使用来自不同组织类型的大量RNA-Seq读数和NCBI的真核注释管道,我们发现了28162个基因,其中8061个是非编码基因。我们的新基因组组装和注释被NCBI标记为RefSeq基因组,并为涉及S.scovelli的研究工作提供了更多的资源。.
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引用次数: 0
PhysiCOOL: A generalized framework for model Calibration and Optimization Of modeLing projects PhysiCOOL:modeLing项目模型校准和优化的通用框架
Pub Date : 2023-02-13 DOI: 10.1101/2022.11.17.516671
Inês G. Gonçalves, D. Hormuth, Sandhya Prabhakaran, C. Phillips, J. García-Aznar
In silico models of biological systems are usually very complex and rely on several parameters describing physical and biological properties that require validation. As such, parameter space exploration is an essential component of computational model development to fully characterize and validate simulation results. Experimental data may also be used to constrain parameter space (or enable model calibration) to enhance the biological relevance of model parameters. One widely used computational platform in the mathematical biology community is PhysiCell which provides a standardized approach to agent-based models of biological phenomena at different time and spatial scales. Nonetheless, one limitation of PhysiCell is that there has not been a generalized approach for parameter space exploration and calibration that can be run without high-performance computing access. Taking this into account, we present PhysiCOOL, an open-source Python library tailored to create standardized calibration and optimization routines of PhysiCell models. Graphical abstract
生物系统的计算机模型通常非常复杂,并且依赖于描述需要验证的物理和生物特性的几个参数。因此,参数空间探索是计算模型开发的重要组成部分,以充分表征和验证模拟结果。实验数据也可用于约束参数空间(或实现模型校准),以增强模型参数的生物学相关性。数学生物学界广泛使用的一个计算平台是PhysiCell,它为不同时间和空间尺度的生物现象的基于主体的模型提供了一种标准化方法。尽管如此,PhysiCell的一个局限性是,还没有一种用于参数空间探索和校准的通用方法,可以在没有高性能计算访问的情况下运行。考虑到这一点,我们推出了PhysiCOOL,这是一个开源Python库,专门用于创建PhysiCell模型的标准化校准和优化例程。图形摘要
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引用次数: 1
Nanopore-based enrichment of antimicrobial resistance genes - a case-based study. 基于纳米孔的抗菌药耐药性基因富集--一项基于案例的研究。
Pub Date : 2023-01-25 eCollection Date: 2023-01-01 DOI: 10.46471/gigabyte.75
Adrian Viehweger, Mike Marquet, Martin Hölzer, Nadine Dietze, Mathias W Pletz, Christian Brandt

Rapid screening of hospital admissions to detect asymptomatic carriers of resistant bacteria can prevent pathogen outbreaks. However, the resulting isolates rarely have their genome sequenced due to cost constraints and long turn-around times to get and process the data, limiting their usefulness to the practitioner. Here we used real-time, on-device target enrichment ("adaptive") sequencing as a highly multiplexed assay covering 1,147 antimicrobial resistance genes. We compared its utility against standard and metagenomic sequencing, focusing on an isolate of Raoultella ornithinolytica harbouring three carbapenemases (NDM, KPC, VIM). Based on this experimental data, we then modelled the influence of several variables on the enrichment results and predicted the large effect of nucleotide identity (higher is better) and read length (shorter is better). Lastly, we showed how all relevant resistance genes are detected using adaptive sequencing on a miniature ("Flongle") flow cell, motivating its use in a clinical setting to monitor similar cases and their surroundings.

对入院患者进行快速筛查,检测出无症状的耐药细菌携带者,可以防止病原体爆发。然而,由于成本限制以及获取和处理数据的周转时间过长,由此产生的分离物很少进行基因组测序,从而限制了它们对从业人员的有用性。在这里,我们使用实时、设备上目标富集("自适应")测序作为一种高度复用的检测方法,涵盖了 1,147 个抗菌药耐药性基因。我们将其用途与标准测序和元基因组测序进行了比较,重点研究了携带三种碳青霉烯酶(NDM、KPC、VIM)的鸟疫杆菌分离物。根据这些实验数据,我们模拟了几个变量对富集结果的影响,并预测了核苷酸同一性(越高越好)和读取长度(越短越好)的巨大影响。最后,我们展示了如何在微型("Flongle")流式细胞上使用自适应测序技术检测所有相关的耐药基因,从而推动其在临床环境中的应用,以监测类似病例及其周围环境。
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引用次数: 0
Improvements to the Gulf pipefish Syngnathus scovelli genome 海湾管鱼(Syngnathus scovelli)基因组的改良
Pub Date : 2023-01-20 DOI: 10.1101/2023.01.23.525209
B. Ramesh, CM Small, H. Healey, B. Johnson, E. Barker, M. Currey, S. Bassham, M. Myers, WA Cresko, Ag Jones
The Gulf pipefish Syngnathus scovelli has emerged as an important species in the study of sexual selection, development, and physiology, among other topics. The fish family Syngnathidae, which includes pipefishes, seahorses, and seadragons, has become an increasingly attractive target for comparative research in ecological and evolutionary genomics. These endeavors depend on having a high-quality genome assembly and annotation. However, the first version of the S. scovelli genome assembly was generated by short-read sequencing and annotated using a small set of RNA-sequence data, resulting in limited contiguity and a relatively poor annotation. Here, we present an improved genome assembly and an enhanced annotation, resulting in a new official gene set for S. scovelli. By using PacBio long-read high-fidelity (Hi-Fi) sequences and a proximity ligation (Hi-C) library, we fill small gaps and join the contigs to obtain 22 chromosome-level scaffolds. Compared to the previously published genome, the gaps in our novel genome assembly are smaller, the N75 is much larger (13.3 Mb), and this new genome is around 95% BUSCO complete. The precision of the gene models in the NCBI’s eukaryotic annotation pipeline was enhanced by using a large body of RNA-Seq reads from different tissue types, leading to the discovery of 28,162 genes, of which 8,061 were non-coding genes. This new genome assembly and the annotation are tagged as a RefSeq genome by NCBI and thus provide substantially enhanced genomic resources for future research involving S. scovelli.
墨西哥湾管鱼Syngnathus scovelli已成为性别选择、发育和生理学等研究领域的重要物种。包括管鱼、海马和海龙在内的鱼类科Syngnathidae已成为生态和进化基因组学比较研究的一个越来越有吸引力的目标。这些努力依赖于高质量的基因组组装和注释。然而,第一个版本的S.scovelli基因组组装是通过短读测序生成的,并使用一小组RNA序列数据进行注释,导致邻接性有限,注释相对较差。在这里,我们提出了一个改进的基因组组装和增强的注释,从而为S.scovelli产生了一个新的官方基因集。通过使用PacBio长读高保真(Hi-Fi)序列和邻近连接(Hi-C)文库,我们填补了小间隙并连接了重叠群,获得了22个染色体水平的支架。与之前发表的基因组相比,我们新基因组组装中的缺口更小,N75要大得多(13.3Mb),并且这个新基因组的BUSCO完整率约为95%。通过使用来自不同组织类型的大量RNA-Seq读数,NCBI真核注释管道中基因模型的精度得到了提高,从而发现了28162个基因,其中8061个是非编码基因。这种新的基因组组装和注释被NCBI标记为RefSeq基因组,从而为未来涉及S.scovelli的研究提供了显著增强的基因组资源。
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引用次数: 1
Distribution of mosquitoes (Diptera: Culicidae) in Thailand: a dataset. 泰国蚊类分布(双翅目:库蚊科):a dataset。
Pub Date : 2023-01-01 DOI: 10.46471/gigabyte.90
Chutipong Sukkanon, Wannapa Suwonkerd, Kanutcharee Thanispong, Manop Saeung, Pairpailin Jhaiaun, Suntorn Pimnon, Kanaphot Thongkhao, Sylvie Manguin, Theeraphap Chareonviriyaphap

Mosquitoes play a crucial role as primary vectors for various infectious diseases in Thailand. Therefore, accurate distribution information is vital for effectively combating and better controlling mosquito-borne diseases. Here, we present a curated dataset of the mosquito distribution in Thailand comprising 12,278 records of at least 117 mosquito species (Diptera: Culicidae). The main genera included in the dataset are Aedes, Anopheles, Armigeres, Culex, and Mansonia. From 2007 to 2023, data were collected through routine mosquito surveillance and research projects from 1,725 locations across 66 (out of 77) Thai provinces. The majority of the data were extracted from a Thai database of the Thailand Malaria Elimination Program. To facilitate broader access to mosquito-related data and support further exploration of the Thai mosquito fauna, the data were translated into English. Our dataset has been published in the Global Biodiversity Information Facility, making it available for researchers worldwide.

在泰国,蚊子作为各种传染病的主要媒介发挥着至关重要的作用。因此,准确的分布信息对于有效防治和更好地控制蚊媒疾病至关重要。在这里,我们提出了一个泰国蚊子分布的精心整理的数据集,其中包括至少117种蚊子(双翅目:库蚊科)的12,278条记录。数据集中的主要属有伊蚊、按蚊、阿蚊、库蚊和曼蚊。从2007年至2023年,通过常规蚊虫监测和研究项目从泰国66个省(77个省中的66个省)的1725个地点收集了数据。大多数数据是从泰国疟疾消除计划的泰国数据库中提取的。为了方便更广泛地获取与蚊子有关的数据,并支持对泰国蚊子区系的进一步探索,这些数据被翻译成英文。我们的数据集已经发表在全球生物多样性信息设施上,供全世界的研究人员使用。
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引用次数: 0
HTGQC and shinyHTGQC: an R package and shinyR application for quality controls of HTG EDGE-seq protocols. HTGQC 和 shinyHTGQC:用于 HTG EDGE-seq 协议质量控制的 R 软件包和 shinyR 应用程序。
Pub Date : 2022-12-02 eCollection Date: 2022-01-01 DOI: 10.46471/gigabyte.74
Lodovico Terzi di Bergamo, Francesca Guidetti, Davide Rossi, Francesco Bertoni, Luciano Cascione

Extraction-free HTG EdgeSeq protocols are used to profile sets of genes and measure their expression. Thus, these protocols are frequently used to characterise tumours and their microenvironments. However, although positive and control genes are provided, little indication is given concerning the assessment of the technical success of each sample within the sequencing run. We developed HTGQC, an R package for the quality control of HTG EdgeSeq protocols. Additionally, shinyHTGQC is a shiny application for users without computing knowledge, providing an easy-to-use interface for data quality control and visualisation. Quality checks can be performed on the raw sequencing outputs, and samples are flagged as FAIL or ALERT based on the expression levels of the positive and negative control genes.

Availability & implementation: The code is freely available at https://github.com/LodovicoTerzi/HTGQC (R package) and https://lodovico.shinyapps.io/shinyHTGQC/ (shiny application), including test datasets.

免提取 HTG EdgeSeq 协议用于描述基因集并测量其表达。因此,这些方案常用于描述肿瘤及其微环境的特征。然而,虽然提供了阳性基因和对照基因,但几乎没有说明如何评估测序运行中每个样本的技术成功率。我们开发了 HTGQC,这是一个用于 HTG EdgeSeq 方案质量控制的 R 软件包。此外,shinyHTGQC 是一款面向无计算知识用户的shiny应用程序,为数据质量控制和可视化提供了一个易于使用的界面。可对原始测序输出进行质量检查,并根据阳性和阴性对照基因的表达水平将样本标记为FAIL或ALERT:代码可在 https://github.com/LodovicoTerzi/HTGQC(R 软件包)和 https://lodovico.shinyapps.io/shinyHTGQC/(shiny 应用程序)上免费获取,包括测试数据集。
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引用次数: 0
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GigaByte (Hong Kong, China)
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