Cross-Platform and Graphical Software Tool for Adaptive LC/MS and GC/MS Metabolomics Data Preprocessing

项目总结/摘要 数据预处理对于任何基于MS的非靶向代谢组学研究的成功至关重要，因为它是第一个 信息学的一步，使数据的意义。尽管现有的软件工具 尽管对代谢组学的研究取得了很大进展，但化合物鉴定和相对定量的错误仍然困扰着该领域。 随着LC/MS和GC/MS平台的灵敏度不断提高，这个问题变得越来越严重。 预处理涉及LC/MS的峰检测、峰分组和注释或LC/MS的光谱去卷积。 GC/MS数据和峰对齐。现有的软件工具总是产生大量的假阳性 和假阴性峰，产生不准确的峰组，未对齐检测到的峰， 相对代谢物定量信息。这些错误可能会在下游转化为虚假或丢失 化合物鉴定，并导致代谢组学的误导性解释。此外，用户需要 为现有软件工具的工作指定大量参数。一般用户通常 不了解如何优化这些参数，并最大化一个方面（例如，敏感性）通常具有 对另一个的有害影响（例如，特异性）。我们将通过开发更准确的 用于提高数据预处理的严谨性和可重复性的算法。所提出的算法将是 用Java实现，并与广泛使用的MZmine 2集成，使软件跨平台， 具有丰富的可视化功能。此外，该实现将针对内存进行优化 效率和计算速度允许大规模数据预处理。对软件的广泛测试将 与代谢组学核心设施和世界各地的用户密切合作进行。

Project Summary / Abstract Data preprocessing is critical for the success of any MS-based untargeted metabolomics study, as it is the first informatics step for making sense of the data. Despite the enormous contributions that existing software tools have made to metabolomics, errors in compound identification and relative quantitation are still plaguing the field. This issue is becoming more serious as the sensitivity of LC/MS and GC/MS platforms is constantly increasing. Preprocessing involves peak detection, peak grouping and annotation for LC/MS or spectral deconvolution for GC/MS data, and peak alignment. Existing software tools invariably yield an immense number of false positive and false negative peaks, produce inaccurate peak groups, mis-align detected peaks, and extract inaccurate information of relative metabolite quantitation. These errors can translate downstream into spurious or missing compound identifications and cause misleading interpretations of the metabolome. Furthermore, users need to specify a large number of parameters for existing software tools to work. Unfortunately, general users usually do not understand how to optimize these parameters, and maximizing one aspect (e.g., sensitivity) often has deleterious effects on another (e.g., specificity). We will address these challenges by developing more accurate algorithms for improving the rigor and reproducibility of data preprocessing. The proposed algorithms will be implemented in Java and integrated with the widely-used MZmine 2, making the software cross-platform and user-friendly with rich visualization capabilities. In addition, the implementation will be optimized for memory efficiency and computing speed allowing large-scale data preprocessing. Extensive testing of the software will be conducted in close collaborations with metabolomics core facilities and users around the world.