Metabolomics Shared Resource

摘要 代谢组学共享资源（MeSR）为UHCC成员和研究人员提供优质的 获得专家建议、咨询和技术支持服务，以使用先进的代谢组学 和生物信息学技术的研究跨越整个范围的癌症研究领域所代表的 中心UHCC研究人员进行的研究需要测量内源性代谢物， 发现与生物学结果或疾病风险的关联，并确保信息的一致性和相关性。 体外模型这些研究涵盖了各种基因突变、“生活方式”暴露（饮食、吸烟）和自然环境。 产品干预。测量生物样品中的大量代谢物或代谢物标记物 需要精密的仪器和专业技术。质谱（MS）代谢 分析方法已越来越多地应用于试图了解代谢组学如何 哺乳动物生物流体（血清/血浆或尿液）、肿瘤组织、细胞系（裂解物）由于代谢产物的改变而改变。 癌症的转化在MS代谢分析应用于常规细胞、临床和免疫学方面仍然存在挑战。 和生物医学研究。我们的总体假设是，基于MS的高通量代谢组学平台可以 鉴定和表征与癌症有关代谢物标志物和机制途径 发展或治疗。生物制剂中低浓度水平下目标代谢物的性质 样品经常对样品制备和分析提出独特的挑战。经过验证的代谢组学 尽管在实验室中提供了许多方法，但组学数据分析也可能具有挑战性，特别是因为生物学和 健康结果取决于暴露于药物或多种药剂，通常需要同时 癌症或治疗的多组生物标志物的测量以及整合的信息学和统计学 分析所产生的“大数据”集。MeSR通过以下具体目标应对这些挑战： 1)为需要使用代谢组学平台的研究的设计和执行提供咨询 癌症研究技术; 2）提供方法开发方面的专业知识，包括样品制备， 能够检测和定量复杂样品中的低浓度或挥发性代谢物; 3）提供 代谢组学分析的统计和信息学方法的咨询和实际援助 使用上述目标所述服务生成的数据集;以及4）提供以下方面的教育和培训 癌症研究的代谢组学方法。MeSR由经验丰富的专业人员运营， 对仪器调度和访问、数据的技术监督、控制和监测机制到位 存档和分析、质量控制和质量保证。实验室有足够的容量容纳 从UHCC研究计划发起的新研究;研究人员经常有效地使用这些设施 需要新方法开发、初步可行性研究和测定验证。

ABSTRACT The Metabolomics Shared Resource (MeSR) provides UHCC members and researchers with premium access to expert advice, consultation and technical support services to enable use of advanced metabolomics and bioinformatics technologies for studies spanning the entire range of cancer research areas represented in the center. Research conducted by UHCC investigators requires measurements of endogenous metabolites to discover associations with biological outcomes or disease risk and ensure the consistency and relevance of in vitro models. These studies span various genetic mutations, “lifestyle” exposures (diet, smoking), and natural product interventions. Measurement of a large panel of metabolites or metabolite markers in biological samples requires sophisticated instrumentation and technical expertise. Mass spectroscopic (MS)-based metabolic profiling approaches have been increasingly applied to in an attempt to understand how metabolome of mammalian biofluids (serum/plasma or urine), tumor tissues, cell lines (lysates) alter as a result of metabolic transformation in cancer. Challenges remain in the application of MS metabolic profiling to routine cellular, clinical and biomedical studies. Our overall hypothesis is that an MS-based, high-throughput metabolomics platform can identify and characterize metabolite markers and mechanistic pathways that are implicated in cancer development or treatment. The properties of the target metabolites at low concentration levels in biological samples frequently present unique challenges for sample preparation and analysis. With validated metabolomics methods offered in the lab, the omics data analysis can also be challenging, particularly since biological and health outcomes are dictated by exposures to drugs or multiple agents often requiring simultaneous measurements of multi-panel biomarkers of a cancer or a treatment and integrated informatics and statistical analysis of the resulting "big data” sets. MeSR addresses these challenges through the following Specific Aims: 1) provide consultation in the design and execution of studies that require use of metabolomics platform technologies for cancer research; 2) provide expertise in method development including sample preparation to enable detection and quantitation of low-concentration or volatile metabolites in complex samples; 3) provide consultation and practical assistance with statistical and informatics methods for the analysis of metabolomics datasets generated using the services described in the preceding aims; and 4) provide education and training in metabolomics methods for cancer research. MeSR is operated by experienced professional staff with effective mechanisms in place for technical oversight, control and monitoring of instrument scheduling and access, data archiving and analysis, quality control and quality assurance. The lab has sufficient capacity to accommodate new research initiated from UHCC research programs; effective use of these facilities by researchers often requires new method development, initial feasibility studies, and assay validation.