New Advances in Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry for Accelerating Biomarker Discovery in Metabolomics

多段注射-毛细管电泳-质谱法加速代谢组学生物标志物发现的新进展

• 批准号: RGPIN-2020-06630
• 负责人: BritzMcKibbin, Philip
• 金额: $ 4.66万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=718401
• 关键词: New; Advances; Multisegment; Injection; Capillary

Metabolomics is a multidisciplinary area of discovery-based research whose aim is the comprehensive analysis of low molecular weight metabolites (overcome these obstacles by developing cutting-edge methodologies based on multisegment injection capillary electrophoresis-mass spectrometry (MSI-CE-MS) technology that offers a transformative approach to metabolomics with high sample throughput, stringent quality control and long-term batch-correction. Our proposal will greatly expand metabolome coverage to enable rapid, sensitive yet robust analyses spanning hydrophilic metabolites and intact phospholipids, including low abundance metabolites of biological significance, such as D-amino acids, biogenic amines, and vitamin D. This will be achieved by developing compatible nonaqueous buffer systems in conjunction with chemoselective derivatization strategies while using a novel nanospray ion source to boost concentration sensitivity. Since mass spectral information is encoded temporally within a separation, open-access software tools will be developed to enable automated processing of MSI-CE-MS data that is unsurpassed in throughput, reproducibility, and data fidelity as compared to conventional LC-MS, GC-MS and NMR platforms. Also, fundamental studies of the electrophoretic mobility of solvated ions and their gas-phase ionization responses will be investigated for diverse classes of metabolites as a way to conduct virtual metabololomic studies; this work will provide an innovative strategy to identify and quantify unknown metabolites based on their putative chemical structure complementary to high resolution MS/MS when chemical standards are lacking, and mass spectral databases remain incomplete. Our research program will also use state-of-the-art MSI-CE-MS methods as applied to the functional analysis of the human microbiome based on characterization of the fecal metabolome, as well as the identification of new chemical signatures associated with smoke exposure in firefighters from volume-restricted biospecimens, including sweat using a non-invasive collection device. This timely proposal will deliver groundbreaking analytical technology, integrative software tools, and accelerated data workflows for biomarker discovery in support of global metabolomic initiatives that also has strong commercial potential with direct impacts on public policy in Canada.

代谢组学是一个以发现为基础的多学科研究领域，其目标是全面分析低分子代谢物(通过开发基于多段注射毛细管电泳质谱(MSI-CE-MS)技术的尖端方法来克服这些障碍，该技术为代谢组学提供了一种具有高样品吞吐量、严格质量控制和长期批量校正的变革性方法。我们的建议将极大地扩大代谢组覆盖范围，以实现对亲水性代谢物和完整磷脂(包括具有生物学意义的低丰度代谢物，如D-氨基酸、生物胺和维生素D)的快速、灵敏而稳健的分析。这将通过开发兼容的非水缓冲系统与化学选择性衍生化策略相结合实现，同时使用新型纳米旋光离子源来提高浓度灵敏度。由于质谱学信息在时间上是在分离中编码的，将开发开放获取的软件工具，以实现MSI-CE-MS数据的自动化处理，与传统的LC-MS、GC-MS和核磁共振平台相比，MSI-CE-MS数据在吞吐量、重复性和数据保真度方面都是无与伦比的。此外，将对不同类别的代谢物进行溶剂化离子的电泳性及其气相电离响应的基础研究，作为进行虚拟代谢组学研究的一种方式；这项工作将提供一种创新的战略，在缺乏化学标准且质谱库仍然不完整的情况下，根据未知代谢物的假定化学结构补充高分辨率MS/MS。我们的研究计划还将使用最先进的MSI-CE-MS方法，应用于基于粪便代谢组特征的人类微生物组的功能分析，以及识别与容量限制生物样本中的消防员烟雾暴露相关的新化学特征，包括使用非侵入性收集设备的汗液。这一及时的提案将提供突破性的分析技术、集成的软件工具和加速的生物标记物发现数据工作流程，以支持全球代谢组倡议，这些倡议也具有强大的商业潜力，对加拿大的公共政策产生直接影响。