Modeling phenotypic transitions in gene expression state space

基因表达状态空间中的表型转变建模

基本信息

  • 批准号:
    8496088
  • 负责人:
  • 金额:
    $ 21.72万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-09-01 至 2016-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): One of the greatest challenges in modern biomedical research is to understand the link between genotype and phenotype and, more importantly, to create models that allow us to predict the response of biological systems to various perturbations that can affect them. Despite an explosion of data that has emerged from genomic technologies, and continued efforts to develop models that capture the complexity of biological systems, we have not yet made significant progress in achieving these goals. Here we propose to develop new, phenomenological approaches that leverage empirical data together with information from other sources such as the biomedical literature, to create predictive models that can be further tested and validated. To understand the global properties of transcriptional networks and to predict the elements with the greatest potential to effect phenotypic changes, we will map our models to thermodynamic spin systems which allow us to identify robust gene modules and associated order parameters. We hypothesize that these order parameters drive phenotypic transitions in a manner analogous to the pressure and temperature dependent phase transitions of water between solid, liquid and gas. To develop and test this approach, we will use data currently being generated through the NHGRI-funded Center for Excellence in Genome Science (CEGS) program in which we are investigating the mechanisms by which oncovirus-derived genes perturb cellular networks to drive cellular transformation. The modules we identify will be used to make concrete predictions about key parameters essential for transformation and these predictions will be tested by using RNAi to perturb the cellular networks and evaluating the response by gene expression analysis and phenotypic assays. Working with my mentor, Dr. John Quackenbush, and co-mentors, Dr. Karl Munger and Dr. Giovanni Parmigiani, this project will allow me to develop a research program that will facilitate my transition from physics to biology and help me to secure an independent research position. To further support my career development, my mentors and I have developed a rigorous training program that will provide me with formal training in statistics and computational biology, and hands-on training in modern laboratory molecular biology.
描述(申请人提供):现代生物医学研究中最大的挑战之一是了解基因型和表型之间的联系,更重要的是,创建允许我们预测生物系统对可能影响它们的各种扰动的反应的模型。尽管基因组技术产生了爆炸性的数据,并继续努力开发捕捉生物系统复杂性的模型,但我们在实现这些目标方面尚未取得重大进展。在这里,我们建议开发新的现象学方法,利用经验数据以及来自其他来源的信息,如生物医学文献,来创建可以进一步测试和验证的预测模型。为了了解转录网络的全球属性并预测最有可能影响表型变化的元件,我们将把我们的模型映射到热力学自旋系统,这使我们能够识别强大的基因模块和相关的顺序参数。我们假设这些序参数驱动表型转变的方式类似于水在固体、液体和气体之间的依赖压力和温度的相变。为了开发和测试这种方法,我们将使用目前通过NHGRI资助的基因组科学卓越中心(CEGS)计划产生的数据,在该计划中,我们正在研究肿瘤病毒衍生基因扰乱细胞网络以驱动细胞转化的机制。我们确定的模块将用于对转化所必需的关键参数进行具体预测,这些预测将通过使用RNAi干扰细胞网络并通过基因表达分析和表型分析评估响应来验证。与我的导师John QuackenBush博士以及共同导师Karl Munger博士和Giovanni Parmigiani博士合作,这个项目将使我能够制定一个研究计划,促进我从物理学向生物学的过渡,并帮助我获得一个独立的研究职位。为了进一步支持我的职业发展,我和我的导师们制定了一个严格的培训计划,为我提供统计学和计算生物学方面的正式培训,以及现代实验室分子生物学的实践培训。

项目成果

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专利数量(0)

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Megha Padi其他文献

Megha Padi的其他文献

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{{ truncateString('Megha Padi', 18)}}的其他基金

Unraveling the regulatory circuits that drive Merkel cell carcinoma
解开驱动默克尔细胞癌的调节回路
  • 批准号:
    10296295
  • 财政年份:
    2021
  • 资助金额:
    $ 21.72万
  • 项目类别:
Unraveling the regulatory circuits that drive Merkel cell carcinoma
解开驱动默克尔细胞癌的调节回路
  • 批准号:
    10669054
  • 财政年份:
    2021
  • 资助金额:
    $ 21.72万
  • 项目类别:
Unraveling the regulatory circuits that drive Merkel cell carcinoma
解开驱动默克尔细胞癌的调节回路
  • 批准号:
    10462667
  • 财政年份:
    2021
  • 资助金额:
    $ 21.72万
  • 项目类别:
Modeling phenotypic transitions in gene expression state space
基因表达状态空间中的表型转变建模
  • 批准号:
    8189557
  • 财政年份:
    2011
  • 资助金额:
    $ 21.72万
  • 项目类别:
Modeling phenotypic transitions in gene expression state space
基因表达状态空间中的表型转变建模
  • 批准号:
    8326605
  • 财政年份:
    2011
  • 资助金额:
    $ 21.72万
  • 项目类别:
Modeling phenotypic transitions in gene expression state space
基因表达状态空间中的表型转变建模
  • 批准号:
    8675899
  • 财政年份:
    2011
  • 资助金额:
    $ 21.72万
  • 项目类别:
Modeling Phase Transitions in Gene Expression State Space
基因表达状态空间中的相变建模
  • 批准号:
    7997748
  • 财政年份:
    2011
  • 资助金额:
    $ 21.72万
  • 项目类别:
Modeling phenotypic transitions in gene expression state space
基因表达状态空间中的表型转变建模
  • 批准号:
    8866421
  • 财政年份:
    2011
  • 资助金额:
    $ 21.72万
  • 项目类别:

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