Combinatorial and graph theoretical approach to systems biology and mol. evo.

系统生物学和分子生物学的组合和图论方法。

• 批准号: 8149615
• 负责人: Teresa Przytycka
• 金额: $ 115.56万
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8149615
• 关键词: Binding; Computational Molecular Biology; DNA; Dependency; Disease; Elements; Graph; Insulin-Like-Growth Factor I Receptor; Systems Biology; combinatorial

I continued to study the impact of genetic variations on gene expression and diseases. We have made progress towards extending our recent method of eQTL analysis to epistatic interaction (manuscript in preparation). We also developed a new method that allows to idnetyfy pathways dys-regulated in diseases and genotypic variation that are putative causes of such dys-regulation. In this method we model interaction network as an electric circuit and the flow of information from genotype to gene expression as current flow. A manuscript describing preliminary results of this work has been invited for an oral presentation on the recent Conference on Research in Molecular Computational Biology (RECOMB 2010). My group also continued to work on computational methods for simulation of signal propagation in signaling network. We developed a fuzzy logic based approach and used it to study the combined Epidermal Growth Factor Receptor (EGFR), Insulin-like Growth Factor-1 Receptor (IGF-1R), and Insulin Receptor (IR) signaling network and to elucidate the crosstalk between the component pathways (7). We made the simulation software is freely available (6). Continuing our work on codon usage, we have been able to demonstrate that codon usage is optimized towards avoiding frameshifting errors in translation (1). We used the frame shifting model developed in this paper to further study the robustness to frameshifting errors(5).

我继续研究基因变异对基因表达和疾病的影响。我们已经取得了进展，扩大我们最近的eQTL分析方法上位相互作用（手稿准备）。我们还开发了一种新的方法，可以识别疾病中失调的途径和基因型变异，这些都是这种失调的假定原因。在该方法中，我们将相互作用网络建模为电路，将从基因型到基因表达的信息流建模为电流。 描述这项工作的初步结果的手稿已被邀请在最近的分子计算生物学研究会议（RECOMB 2010）的口头报告。 我的小组还继续研究模拟信令网络中信号传播的计算方法。我们开发了一种基于模糊逻辑的方法，并将其用于研究组合的表皮生长因子受体（EGFR）、胰岛素样生长因子-1受体（IGF-1 R）和胰岛素受体（IR）信号传导网络，并阐明组分途径之间的串扰（7）。我们制作的模拟软件是免费提供的（6）。 继续我们关于密码子使用的工作，我们已经能够证明密码子使用是优化的，以避免翻译中的移码错误（1）。我们使用本文开发的移帧模型来进一步研究对移帧错误的鲁棒性（5）。