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

我继续研究基因变异对基因表达和疾病的影响。我们在将我们最新的eQTL分析方法扩展到上位性互作方面取得了进展(手稿正在准备中)。我们还开发了一种新的方法，可以识别疾病和基因变异中异常调控的通路，这些疾病和基因变异可能是导致这种异常调控的原因。在该方法中，我们将相互作用网络建模为电路，将从基因到基因表达的信息流建模为电流流。描述这项工作初步成果的手稿已被邀请在最近举行的分子计算生物学研究会议(RECOMB 2010)上作口头介绍。 我的团队还继续致力于信令网络中信号传播模拟的计算方法。我们发展了一种基于模糊逻辑的方法，并用它来研究表皮生长因子受体(EGFR)、胰岛素样生长因子-1受体(IGF-1R)和胰岛素受体(IR)信号网络的组合，并阐明了各组成部分之间的串扰(7)。我们使得仿真软件是免费的(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的使用是为了避免翻译中的移码错误而优化的(1)。我们利用本文提出的移帧模型进一步研究了移帧误差的鲁棒性(5)。

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).