EnteroBase: A Powerful, User-Friendly Online Resource for Analyzing and Visualizing Genomic Variation within Escherichia coli and Salmonella enterica

对于科学家、政策制定者和公众来说，很难想象有哪两种生物比大肠杆菌和肠杆菌更重要。这两种细菌都在实验室作为细菌细胞功能、行为和进化的模型进行了广泛的研究。然而，这两种病毒也都是人和动物感染的重要原因，很少出现在新闻中，特别是考虑到它们容易引发疫情。2011年德国爆发的大肠杆菌疫情，导致4000例病例和50例死亡，充分表明了这些细菌的力量，即使是在富裕的先进社会也是如此。2013年，英国媒体报道了沙门氏菌，当时有200人在纽卡斯尔的香料节后患病。重要的是要认识到，没有单一的菌株可以捕捉到这两个物种的精髓。相反，我们在大自然中看到的是丰富多彩的多样性。例如，一些大肠杆菌菌株生活在我们的肠道中是无害的，而另一些菌株则会导致腹泻、尿路感染甚至血液感染。两个大肠杆菌菌株可能有1/3的基因组成(基因组)不同。沙门氏菌和大肠杆菌都经历了无情的进化，包括抗生素耐药性的传播。已经存在的巨大多样性，加上正在进行的新谱系的进化和传播，给微生物学家和其他科学家以及政策制定者在识别和分类菌株类型方面带来了巨大的问题。然而，在科学、临床甚至政治结论可以在亚型或物种中推广之前，这种对定义明确、科学可靠的种群的分类是至关重要的。幸运的是，我们获得了一个令人兴奋的新机会，以高通量测序的形式捕捉和分析细菌物种内的多样性，这是一套创新技术，使细菌基因组测序(捕获细胞内所有DNA序列的过程)比以往任何时候都更容易、更便宜、更快。然而，新数据的突然出现带来了一个新的挑战--从消防水管中喝水的问题--即如何存储、可视化和分析这项令人兴奋的新技术产生的关于基因组多样性的所有新数据。此外，虽然专业的生物信息学家可以使用命令行工具来分析基因组，但基于实验室的细菌学家如果不想错过这个令人兴奋的新机会，就必须依赖于创建新的用户友好的基于网络的资源。为了解决这个问题，我们将创建一个新的、强大但用户友好的在线数据库，名为ENTEROBASE，它将为任何有兴趣分析和可视化大肠杆菌和沙门氏菌遗传多样性的人提供一站式服务。EnteroBase将纳入ENTEROTOOLS，这是一套模块化的、开源的、基于网络的工具，与当前和未来测序技术的数据格式和标准兼容。这两个资源加在一起，将使在实验室工作、缺乏高级计算机技能的细菌学家能够对细菌DNA序列数据进行深入和复杂的计算机分析。用户将能够上传和分析他们自己的数据，以及利用微生物界积累的知识，不仅可以查看这些物种的全球多样性模式，还可以对正在进行或最近爆发的细菌进行快速、接近实时的分析。首席研究员阿克特曼带头努力用更现代的方法取代过时的19世纪和20世纪的这些细菌的分型和分类方法；合作研究员帕伦应用了创新的方法来分析德国的大肠杆菌疫情。这两个项目都将为这个项目带来数以千计的用户，这些用户以前使用的是类似的、成熟的但功能较差的数据库。该项目还将有助于维护和加强英国的技能基础，并使我国成为最聪明和最优秀的科学家的首选目的地。

It is hard to think of two organisms that are more important to scientists, policy makers and the public than E. coli and S. enterica. Both have been studied extensively in the laboratory as models of how bacterial cells function, behave and evolve. However, both are also important causes of human and animal INFECTION and are seldom out of the news, particularly given their propensity to cause outbreaks. The E. coli outbreak that hit Germany in 2011, with >4,000 cases and >50 deaths, amply illustrates the power of these organisms to devastate even a wealthy advanced society. In 2013, Salmonella gained media coverage in England when >200 people fell ill after a spice festival in Newcastle.It is important to recognise that no single strain can capture the essence of either species. Instead, what we see in nature is a riotous profusion of diversity. For example, some strains of E. coli live harmlessly in our bowels, while others cause diarrhoea, urinary tract infection or even bloodstream infection. Two E. coli strains may differ by 1/3 of their genetic make-up (genome). Both Salmonella and E. coli undergo relentless evolution, including spread of ANTIBIOTIC RESISTANCE. The huge diversity already present, twinned with ongoing evolution and spread of new lineages creates tremendous problems for microbiologists and other scientists as well as policy makers in recognising and classifying strain types. Yet such classification into well-defined, scientifically robust populations is essential before scientific, clinical or even political conclusions can be generalised across sub-types or species.Fortunately, we have been presented with an exciting new opportunity to capture and analyse within-species diversity in bacteria in the form of HIGH-THROUGHPUT SEQUENCING, a set of innovative technologies that make bacterial genome sequencing (a process of capturing all the DNA sequences within the cell) easier, cheaper and quicker than ever before. However, this sudden availability of new data creates a fresh challenge-the DRINKING-FROM-A-FIRE-HOSE problem-namely how to store, visualise and analyse all the new data on genomic diversity generated by this exciting new technology. In addition, while expert bioinformaticians can use command-line tools to analyse genomes, lab-based bacteriologists are dependent on the creation of new user-friendly web-based resources, if they are not to miss out on this exciting new opportunity. To address this problem we will create a new, powerful but user-friendly online database called ENTEROBASE, which will act as a one-stop shop for anyone interested in analysing and visualising genetic diversity in E. coli and Salmonella. EnteroBase will incorporate ENTEROTOOLS, a set of modular, open-source, web-based tools compatible with data formats and standards from both current and future sequencing technologies. Together, these two resources will allow bacteriologists who work in the laboratory and lack high-level computer skills to perform incisive and sophisticated computer-based analyses of bacterial DNA sequence data. Users will be able to upload and analyse their own data, as well as exploit the cumulative knowledge of the microbiology community, not just to look at global patterns of diversity within these species but also to perform speedy, near-real-time analyses of ongoing or recent outbreaks.Principal investigator Achtman has spearheaded efforts to replace outdated 19th- and 20th-century approaches to the typing and classification of these bacteria with more modern approaches; co-investigator Pallen has applied innovative approaches to analyse the German E. coli outbreak. Both will bring to this project 1000s of users of previous similar, well-established but less powerful databases. This project will also help maintain and enhance the UK skills base and make our country the destination of choice for the brightest and best scientists.