Modeling Transcriptional Reprogramming by Markov Chain Monte Carlo Sampling

通过马尔可夫链蒙特卡罗采样模拟转录重编程

基本信息

  • 批准号:
    8236473
  • 负责人:
  • 金额:
    $ 32.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-09-01 至 2013-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Complex diseases, including cancer and multiple sclerosis, arise when multiple biological systems are impacted by molecular changes, such as gene mutation, gene silencing, or cellular modification by external agents. These molecular changes lead to changes in the cellular state, almost always including reprogramming of gene expression. Because biological systems are inherently complex and nonlinear, appropriate modeling of the system is required to recover knowledge of systems-level behavior in many cases. We focus in this proposal on methods to improve our ability to infer biological process activity from high- throughput data and on the development of biomarkers of these processes. We have developed a Markov chain Monte Carlo algorithm for analysis of microarray data that combines knowledge of transcriptional regulation and simple models of signaling networks to identify on-target and off- targets effects of therapeutics in cancer. Here we propose including prior knowledge in this algorithm by integrating data from pathways, gene mutations, methylation arrays, miRNA arrays, and protein-protein interactions (PPIs) to improve inference of cell behavior at a systems-level. Our first aim will develop an integrated model of signaling coupled to transcriptional reprogramming that couples knowledge of pathways to measurements of mutation status and miRNA levels to improve estimation of cell signaling. Our second aim will integrate methylation measurements and transcription factor binding site information as prior data to refine inference of targets of transcription factors to improve gene set inference and estimation of upstream signaling. Our third aim will develop a methodology to find reliable biomarkers from our models in light of multiple regulation of genes. Successful completion of the proposed work will provide novel open-source tools for improved inference on and biomarker identification of transcriptional reprogramming of cells. This will substantially improve inference of the specific changes that drive systems out of homeostasis and of treatment response in individual cases.
描述(由申请人提供):复杂疾病,包括癌症和多发性硬化症,当多个生物系统受到分子变化的影响时,如基因突变、基因沉默或外部因子的细胞修饰。这些分子变化导致细胞状态的变化,几乎总是包括基因表达的重编程。由于生物系统本质上是复杂和非线性的,在许多情况下,需要对系统进行适当的建模来恢复系统级行为的知识。我们在本提案中着重于提高我们从高通量数据推断生物过程活性的能力和开发这些过程的生物标志物的方法。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Michael F Ochs其他文献

Michael F Ochs的其他文献

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{{ truncateString('Michael F Ochs', 18)}}的其他基金

Modeling Transcriptional Reprogramming by Markov Chain Monte Carlo Sampling
通过马尔可夫链蒙特卡罗采样模拟转录重编程
  • 批准号:
    8724559
  • 财政年份:
    2012
  • 资助金额:
    $ 32.8万
  • 项目类别:
An Open-Source Algorithm Isolating Overlapping Signatures in Microarray Data
一种隔离微阵列数据中重叠特征的开源算法
  • 批准号:
    7922313
  • 财政年份:
    2009
  • 资助金额:
    $ 32.8万
  • 项目类别:
An Open-Source Algorithm Isolating Overlapping Signatures in Microarray Data
一种隔离微阵列数据中重叠特征的开源算法
  • 批准号:
    7682309
  • 财政年份:
    2008
  • 资助金额:
    $ 32.8万
  • 项目类别:
An Open-Source Algorithm Isolating Overlapping Signatures in Microarray Data
一种隔离微阵列数据中重叠特征的开源算法
  • 批准号:
    7464236
  • 财政年份:
    2008
  • 资助金额:
    $ 32.8万
  • 项目类别:
Identifying Genetic Factors for Predisposition in Polygenic Diseases
确定多基因疾病易感性的遗传因素
  • 批准号:
    7220047
  • 财政年份:
    2007
  • 资助金额:
    $ 32.8万
  • 项目类别:
Identifying Genetic Factors for Predisposition in Polygenic Diseases
确定多基因疾病易感性的遗传因素
  • 批准号:
    7014706
  • 财政年份:
    2006
  • 资助金额:
    $ 32.8万
  • 项目类别:
Analysis and Annotation Pipeline for Functional Genomics
功能基因组学的分析和注释流程
  • 批准号:
    6867168
  • 财政年份:
    2005
  • 资助金额:
    $ 32.8万
  • 项目类别:
Analysis and Annotation Pipeline for Functional Genomics
功能基因组学的分析和注释流程
  • 批准号:
    7008125
  • 财政年份:
    2005
  • 资助金额:
    $ 32.8万
  • 项目类别:
BIOINFORMATICS
生物信息学
  • 批准号:
    8559551
  • 财政年份:
    1997
  • 资助金额:
    $ 32.8万
  • 项目类别:
BIOINFORMATICS
生物信息学
  • 批准号:
    8559772
  • 财政年份:
  • 资助金额:
    $ 32.8万
  • 项目类别:

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