Open source pipelines for integrated metabolomics analysis by NMR and mass spectrometry

生命科学研究现在通常使用高科技仪器进行，产生有关感兴趣系统的大量数据。这些技术统称为“组学”（例如，包括基因组学、蛋白质组学和代谢组学），它们可以以不同的方式测量基因是如何开启或关闭的，这些基因编码的蛋白质在感兴趣的细胞或组织中是如何表现的，或者当系统正常运行或因疾病、功能障碍或引入有毒物质而受到压力时，代谢物（细胞中的生化分子）是如何大量变化的。所研究的代谢物可以包括为细胞提供能量或结构的分子（如脂肪、糖等）、DNA和蛋白质的结构构建块（如核苷酸、氨基酸）以及生物过程的必要辅助因子（如维生素）。在基础研究和临床情况中，以异常丰度存在的特定代谢物可能是特定状态（如疾病）的指标（生物标志物）。事实上，代谢组学研究被应用于癌症、传染病、心脏病、糖尿病和许多其他疾病的研究中。代谢组学研究中最大的挑战之一是对数据的分析非常困难。从仪器提供的原始数据（主要是核磁共振（NMR）光谱或质谱（MS））到研究人员感兴趣的最终结果，即样品之间特定代谢物的定量和统计显着差异，需要多个不同的处理步骤。有多种软件包（包括商业的和免费的）可以在一个完整的管道中执行单个步骤，但是很少有好的软件可以很容易地执行一个完整的分析。在这个项目中，我们将使用一个名为Galaxy的软件框架，为NMR或MS生成的数据构建这样的软件。Galaxy被设计为在其他软件包之上构建一个网络界面，使不同的（先前断开的）软件包能够连接在一起，形成一个易于使用的管道。模块的连接需要标准化格式的数据文件作为每个步骤的输入和输出，因此我们也将与国际组织合作，帮助商定一个普遍适用的标准格式，以供我们的管道和其他从事代谢组学工作的软件开发人员使用。我们的管道将使科学家更容易分析他们的数据，特别是比较或整合来自两种互补技术（核磁共振和质谱）的数据，以获得正在研究的系统的更完整的图像。这将有助于更多目前缺乏代谢组学详细知识的研究人员接受和利用这一强大的技术。最后，我们将使科学家在发表他们的研究时更容易将他们的数据放入公共数据库，使其他科学家能够验证他们的发现，并在某些情况下在他们自己的实验室中重新分析他们的数据。

Research in the Life Sciences is now commonly performed using high-tech instrumentation, producing very large amounts of data about a system of interest. These techniques are collectively called 'omics (e.g. including genomics, proteomics and metabolomics) - and in different ways can measure how genes are switched on or off, how the proteins encoded by those genes behave in a cell or tissue of interest, or how the metabolites (biochemical molecules in cells) change in abundance, as the system behaves normally or is put under stress by disease, dysfunction or the introduction of toxic substances. The metabolites studied can include molecules that provide energy or structure to cells (e.g. fats, sugars etc), the structural building blocks of DNA and proteins (e.g. nucleotides, amino acids) and essential co-factors to biological processes (e.g. vitamins). In fundamental research, and in clinical situations, the presence of a particular metabolite at an unusual abundance can be an indicator (a biomarker) of a particular state - such as a disease. Indeed, metabolomics research is applied in studies on cancer, infectious disease, heart disease, diabetes and many others. One of the greatest challenges in metabolomics research is that the analysis of the data is very difficult. Multiple different processing steps are needed to get from the raw data as delivered by the instrument - primarily nuclear magnetic resonance (NMR) spectroscopy or mass spectrometry (MS), to the final results the researcher is interested in, i.e. quantitative and statistically significant differences in particular metabolites between samples. There are multiple software packages (both commercial and free) that can perform individual steps within a complete pipeline, but there is very little good software that makes it easy to perform a full analysis. In this project, we will build such software for data generated from NMR or MS, using a software framework called Galaxy. Galaxy has been designed to construct a web interface on top of other software packages, enabling different (previously disconnected) packages to be joined together into an easy to use pipeline. The joining together of modules needs data files in a standardized format as the input and output of each step, so we will also work within international organizations to help agree on a universally applied standard format to be used in our pipeline and by other software developers working in metabolomics. Our pipeline will make it much easier for scientists to analyse their data and, in particular, to compare or integrate data coming from both complementary techniques (NMR and MS) to get a more complete picture of the system being studied. This will facilitate many more researchers - who currently lack detailed knowledge in metabolomics - to embrace and exploit this powerful technology. Lastly, we will make it easier for scientists to put their data into public databases when they publish their research, enabling other scientists to verify their findings and in some cases re-analyse their data in their own labs.