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，很难想象有两种生物比大肠杆菌和肠球菌更重要。两者都在实验室中作为细菌细胞功能、行为和进化的模型进行了广泛的研究。然而，这两种疾病也是人类和动物感染的重要原因，很少被新闻报道，特别是考虑到它们有引起疫情的倾向。2011年，德国爆发了大肠杆菌疫情，造成4000人感染，50人死亡，这充分说明了这些微生物的力量，甚至可以摧毁一个富裕的发达社会。2013年，沙门氏菌在英国获得了媒体的报道，当时纽卡斯尔的一个香料节结束后，有200多人患病。重要的是要认识到，没有一个菌株能够捕捉到任何一个物种的本质。相反，我们在大自然中看到的是丰富多彩的多样性。例如，一些大肠杆菌菌株在我们的肠道中无害，而另一些菌株则会导致腹泻、尿路感染甚至血液感染。两个大肠杆菌菌株的基因组成（基因组）可能有1/3的差异。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，加上正在进行的进化和新谱系的传播，给微生物学家和其他科学家以及决策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推广到各个亚型或物种之前，这种定义明确、科学稳健的种群分类是必不可少的。幸运的是，我们有了一个令人兴奋的新机会，以高通量测序的形式捕获和分析细菌的物种多样性，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，更便宜和更快。然而，新数据的突然可用性带来了一个新的挑战——“从消防水管里喝水”的问题——即如何存储、可视化和分析由这项令人兴奋的新技术产生的所有关于基因组多样性的新数据。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，但实验室细菌学家如果不想错过这个令人兴奋的新机会，则依赖于创建新的用户友好的基于web的资源。为了解决这个问题，我们将创建一个新的、功能强大但用户友好的在线数据库ENTEROBASE，它将为任何对分析和可视化大肠杆菌和沙门氏菌的遗传多样性感兴趣的人提供一站式服务。EnteroBase将整合ENTEROTOOLS，这是一套模块化、开源、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。总之，这两种资源将允许在实验室工作且缺乏高级计算机技能的细菌学家对细菌DNA序列数据进行深刻而复杂的计算机分析。用户将能够上传和分析他们自己的数据，并利用微生物界积累的知识，不仅可以查看这些物种多样性的全球模式，还可以对正在发生或最近发生的疫情进行快速、接近实时的分析。首席研究员阿奇特曼带头努力，用更现代的方法取代过时的19世纪和20世纪的细菌分类和分类方法；合作研究者帕伦采用了创新的方法来分析德国的大肠杆菌爆发。两者都将为这个项目带来以前类似的，完善的，但不太强大的数据库的用户。该项目还将有助于维持和提高英国的技能基础，使我国成为最聪明、最优秀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.