Systems Metabolomics Core

项目总结 急性髓系白血病(AML)神经鞘磷脂代谢的调节和错调发生在 多个生物分子水平--基因突变、酶的丰度和活性，以及鞘糖脂 前体和产品。计划项目的创新方面系统地收集了 累积的患者样本和相关的AML细胞系的生物分子图谱。新的系统代谢组学 CORE(CORE C)将帮助较大的P01项目团队通过整合 来自单个研究项目和其他研究核心的系统级数据集。我们的目标是告知 涉及鞘磷脂靶向治疗的关键项目级决策。核心C将追求以下目标 具体目标：1)根据患者--评估结果和反应的线性和非线性预测模型 特定生物分子和(细胞)遗传学；2)测试数据驱动的结果和反应预测模型 基于患者特定、基因转录物-脂质活性特征；以及3)整合基因、转录物和 具有重建的人类代谢网络鞘脂模块的急性髓系白血病患者的代谢物特征。 核心C领导层由数据驱动的癌症建模、代谢网络重建、 和系统生物学。因此，核心准备调整其方法，以适应不断变化的需求 在P01第二任期内的个人研究项目。

PROJECT SUMMARY The regulation and mis-regulation of sphingolipid metabolism in acute myeloid leukemia (AML) occurs at multiple bio-molecular levels—gene mutation, enzyme abundances and activities, as well as sphingolipid precursors and products. The innovative aspect of the Program Project has systematically collected deep biomolecular profiles of accrued patient samples and relevant AML cell lines. The new Systems Metabolomics Core (Core C) will help the larger P01 project team to generate testable hypotheses by integrating the systems-level datasets from individual research projects and the other research cores. The goal is to inform critical Project-level decisions involving sphingolipid-targeted therapies. Core C will pursue the following Specific Aims: 1) evaluate linear and nonlinear predictive models of outcome and response based on patient- specific biomolecules and (cyto)genetics; 2) test data-driven predictive models of outcomes and response based on patient-specific, gene–transcript–lipid–activity signatures; and 3) integrate gene, transcript, and metabolite profiles of AML patients with a reconstructed sphingolipid module of the human metabolic network. Core C leadership is comprised of experts in data-driven cancer modeling, metabolic network reconstruction, and systems biology. Therefore, the Core is poised to adapt its approaches to the changing needs of the individual research projects over the second term of the P01.