MicrobesNG: A scalable replicable biological sample repository incorporating whole-genome sequence data and analysis of thousands of microbial strains

MicrobesNG：一个可扩展的可复制生物样本库，包含全基因组序列数据和数千种微生物菌株的分析

• 批准号: BB/L024209/1
• 负责人: Ian Henderson
• 金额: $ 133.98万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL024209%2F1
• 关键词: MicrobesNG; scalable; replicable; biological; sample

One of the greatest advances of modern science is the ability to determine the DNA sequences of living organisms. Access to complete DNA sequences has provided researchers, environmentalists, clinicians, law enforcement and industrialists with a myriad of benefits. The information permits a deeper understanding of the diversity of life in the world. Comparing DNA sequences allows researchers to determine relationships between the three kingdoms of life and to infer evolutionary lineages. Understanding the genetic content of animals and plants permits the selection and development of stronger, more disease-resistant plants and animals increasing outputs and reducing waste. Understanding the human and animal genomes has had an enormous impact on the ability of clinicians to determine genetic susceptibility to a variety of diseases; one only has to witness the lives saved by identifying those most at risk of breast cancer and offering early treatment. The ability to harness genome information has allowed industry to develop new therapies for disease and produce new methods for a variety of manufacturing processes e.g. .enzymes are being used to bleach paper pulp. To the lay person, perhaps the most familiar benefit to genomic data is the use of DNA to identify perpetrators of crime. One of the subjects to benefit most from genome sequencing is microbiology. The ability to rapidly obtain genome sequences has allowed researchers to find new bacterial and viral genes which allow pathogens to cause disease. It allows epidemiologists to identify strains in outbreaks of infection and to trace those outbreaks back to the point of origin so further infections can be prevented. Genome sequencing has elucidated mechanisms by which bacteria become resistant to antibiotics allowing clinicians to use a more informed decision making process when prescribing antibiotics. Microbial genomics helps the pharmaceutical industry gain a better understanding of the vulnerabilities of bacteria and viruses, information which is used to identify and develop new drugs. Recently, genomic studies have linked changes in certain bacterial populations growing in and on the human body with non-infectious disease such as obesity and cancer.The tremendous success of genome sequencing has provided us with a problem. Rapid technological advances in DNA sequencing have resulted in the ability of researchers to generate sequence data quicker than it can be analysed and interpreted with current methodologies. This is for a number of different reasons including the development of ad-hoc methods to prepare, analyse and store the data and the lack of standard operating procedures across the discipline. Importantly, the ability to rapidly sequence bacterial genomes in particular, means thousands of strains are being sequenced yet there is no common method for accessing and studying these strains and garnering the benefits of this significant investment of Public money.This proposal seeks to redress some of the problems that have become apparent in the community. We will establish a resource that becomes a paradigm for sequencing bacterial strains, for storing and analysing the genomic data, and for archiving sequenced strains so they can be interrogated later. We will achieve this by (1) establishing best practices for sequencing protocols that deliver maximum output, (2) providing a framework to efficiently manage the storage of collections of bacterial strains, (3) developing software that allows whole-genome sequencing data and meta-data (information on the source, and characteristics of the strain) to be correlated with strains in the store and (4) delivering novel analysis tools to permit the comparison of hundreds or thousands of microbial strains simultaneously, thereby easing the analysis bottleneck. We will make these tools and protocols available to the wider community so that they can be adopted by genome sequencing centres in other disciplines.

现代科学的最大进步之一是能够确定生物体的DNA序列。获得完整的DNA序列为研究人员、环保主义者、临床医生、执法人员和工业家提供了无数的好处。这些信息使人们能够更深入地了解世界上生命的多样性。比较DNA序列使研究人员能够确定生命的三个王国之间的关系，并推断进化谱系。了解动植物的基因内容，就可以选择和培育更强壮、更抗病的动植物，从而增加产量，减少浪费。了解人类和动物的基因组对临床医生确定各种疾病的遗传易感性的能力产生了巨大的影响;人们只需要见证通过识别那些最有可能患乳腺癌的人并提供早期治疗而挽救的生命。利用基因组信息的能力使工业界能够开发新的疾病疗法，并为各种制造工艺生产新的方法，例如酶被用来漂白纸浆。对于外行人来说，也许基因组数据最熟悉的好处是使用DNA来识别犯罪者。从基因组测序中受益最多的学科之一是微生物学。快速获得基因组序列的能力使研究人员能够发现新的细菌和病毒基因，这些基因使病原体能够引起疾病。它使流行病学家能够识别感染爆发中的菌株，并将这些爆发追溯到起源点，以便预防进一步的感染。基因组测序已经阐明了细菌对抗生素产生耐药性的机制，使临床医生在处方抗生素时能够使用更明智的决策过程。微生物基因组学有助于制药行业更好地了解细菌和病毒的脆弱性，这些信息用于识别和开发新药。近年来，基因组研究发现，人体内和体表生长的某些细菌种群的变化与肥胖和癌症等非传染性疾病有关。基因组测序的巨大成功给我们带来了一个问题。DNA测序技术的快速进步使研究人员能够以比现有方法更快的速度生成序列数据。这是由于若干不同的原因，包括制定了准备、分析和储存数据的临时方法，以及缺乏跨学科的标准作业程序。重要的是，特别是快速测序细菌基因组的能力，意味着数以千计的菌株正在被测序，但没有通用的方法来访问和研究这些菌株，并获得这笔巨额公共资金投资的好处。这项建议旨在解决社会上已经变得明显的一些问题。我们将建立一个资源，成为一个范例，用于测序细菌菌株，用于存储和分析基因组数据，并存档测序菌株，以便以后可以查询。我们将通过以下方式实现这一目标：（1）建立测序方案的最佳实践，以提供最大的输出，（2）提供一个框架，以有效地管理细菌菌株集合的存储，（3）开发允许全基因组测序数据和元数据的软件，（关于消息来源的资料，和菌株的特征）与储存中的菌株相关，以及（4）提供新的分析工具，允许同时比较数百或数千种微生物菌株，从而缓解分析瓶颈。我们将向更广泛的社区提供这些工具和协议，以便它们可以被其他学科的基因组测序中心采用。

项目成果

Pseudomonas aeruginosa PA80 is a cystic fibrosis isolate deficient in RhlRI quorum sensing.

• DOI: 10.1038/s41598-021-85100-0
• 发表时间: 2021-03-11
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Ahmed SAKS;Rudden M;Elias SM;Smyth TJ;Marchant R;Banat IM;Dooley JSG
• 通讯作者: Dooley JSG

Nonomuraea terrae sp. nov., isolated from arid soil.

Nonomuraea terrae sp。

• DOI: 10.1007/s00203-020-01941-9
• 发表时间: 2020
• 期刊: Archives of microbiology
• 影响因子: 2.8
• 作者: Ay H

The complete genome sequence of Hafnia alvei A23BA; a potential antibiotic-producing rhizobacterium.

• DOI: 10.1186/s13104-020-05418-2
• 发表时间: 2021-01-06
• 期刊: BMC research notes
• 影响因子: 1.8
• 作者: Awolope OK;O'Driscoll NH;Di Salvo A;Lamb AJ
• 通讯作者: Lamb AJ

Genomic insight into a novel actinobacterium, Actinomadura rubrisoli sp. nov., reveals high potential for bioactive metabolites.

对一种新型放线菌（Actinomadura rubrisoli sp）的基因组见解。

• DOI: 10.1007/s10482-020-01511-5
• 发表时间: 2021
• 期刊: Antonie van Leeuwenhoek
• 作者: Ay H

The first report of Listeria monocytogenes detected in pinnipeds

• DOI: 10.1016/j.jcpa.2023.12.003
• 发表时间: 2024-01-10
• 期刊: JOURNAL OF COMPARATIVE PATHOLOGY
• 影响因子: 0.8
• 作者: Baily，Johanna L.;Paterson，Gavin K.;Dagleish，Mark P.
• 通讯作者: Dagleish，Mark P.