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

现代科学最伟大的进步之一是能够测定活生物体的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、执法人员和实业家提供了无数的好处。这些信息使人们对世界上生命的多样性有了更深的了解。比较DNA序列使研究人员能够确定三个生命王国之间的关系，并推断出进化谱系。了解动物和植物的遗传成分，可以选择和发展更强壮、更抗病的动植物，增加产量，减少浪费。了解人类和动物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；人们只需要通过识别那些最容易患乳腺癌的人并提供早期治疗来挽救生命。利用基因组信息的能力使工业界能够开发治疗疾病的新疗法，并为各种制造过程(例如：酶被用来漂白纸浆。对于外行来说，也许基因组数据最熟悉的好处是使用DNA来识别罪犯。微生物学是基因组测序最受益的学科之一。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，这些基因允许病原体引起疾病。它使流行病学家能够识别感染暴发中的菌株，并将这些暴发追溯到起源点，从而可以预防进一步的感染。基因组测序已经阐明了细菌对抗生素产生耐药性的机制，允许临床医生在开抗生素处方时使用更明智的决策过程。微生物基因组学有助于制药业更好地了解细菌和病毒的脆弱性，这些信息可用于识别和开发新药。最近，基因组研究已经将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联系起来。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得研究人员能够以比现有方法更快的速度生成序列数据。这有许多不同的原因，包括开发专门的方法来准备、分析和存储数据，以及缺乏整个学科的标准操作程序。重要的是，快速测序细菌基因组的能力，特别是，意味着成千上万的菌株正在测序，但没有通用的方法来获取和研究这些菌株，并从这项重大的公共资金投资中获益。这一建议旨在纠正社会上出现的一些明显问题。我们将建立一个资源，它将成为细菌菌株测序的范例，用于存储和分析基因组数据，并将测序菌株存档，以便以后对它们进行查询。我们将通过以下方式实现这一目标：(1)建立提供最大产出的测序方案的最佳实践；(2)提供有效管理菌株集合存储的框架；(3)开发允许全基因组测序数据和元数据（来源信息）的软件；(4)提供新颖的分析工具，允许同时对数百或数千种微生物菌株进行比较，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，以便其他学科的基因组测序中心可以采用它们。

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.