一种基于仿真的预测癌细胞致死基因的方法.docxVIP

一种基于仿真的预测癌细胞致死基因的 方法 许扬郑浩然 中国科学技术大学计算机科学与技术学院 摘要： 口的癌细胞致死基因的研究是治疗癌症的重要尝试，其发现依赖于生物学上的 基因敲除实验。鉴于此类实验的高代价、长周期等不足，本文给出一种基于计算 机仿真的预测癌细胞致死基因的方法，旨在运用计算机仿真技术预测对癌细胞 研究有价值的信息，为基因敲除的牛物实验提供线索，帮助降低实验成木。方法 计算机仿真实验基于人类全基因组代谢网络，融合癌细胞的基因表达数据，用 一种基于约束建模的方法，以预测癌细胞代谢网络屮有活性的反应，并将这些 反应命名为core reactions”，将core reactions”作为输入，重构岀一致 的癌症工作网络。在该网络上，使用基于约束的流量平衡基因敲除算法，获取使 得工作网络biomass产量为0的基因，即致死基因。结果以肾透明细胞癌为例, 根据上述算法，计算结果给出了肾透明细胞癌潜在的7个致死基因。结论 本文 给出一种高通量数据结合代谢网络，构造癌症特异网络，并通过计算机仿真基 因敲除以获取癌细胞致死基因的方法。此方法通用、高效，有助于更好地开展生 物学实验。 关键词： 约束建模;基因敲除;特异网络;致死基因;肾透明细胞癌; 作者简介：郑浩然，副教授。E-ma订:hrzhcng@ustc. cdu. cn 收稿日期:2017-03-13 基金：国家重点基础研究发展计划(2011CB910200) Prediction for the essential genes in cancer cells based on Simulation XU Yang ZHENG Haoran Department of ComputerScience and Technology, University of Science and Technology of China; Abstract： Objective Research on essential genes in cancer cells is an important attempt to treat cancer, its discovery depends on gene knockout experiments. Considering the high cost and long periods of this kind of tests, we present a method for predicting the essential genes in cancer cells based on computer simulation. We aim to use computer simulation techniques to predict valuable information in cancer cell research, provide clues to knockout experiments, and reduce experimental costs. Methods The in silico knockout test is based on the genome-scale human metabol ic network. Integrating the transcriptomics data of cancer cel l s, we use a mat hema tic model to prcdic t the “core reacti ons” of can cor cells. Then these reactions are utilized to reconstruct the cancer cell specific network. The in silico knockout experiment is based on this network. Finally we get the essential genes which make biomass production to be 0 after knockout by using constraint~based flux balanee analysis ( FBA) knockout algorithm. RcsuIts We choose clear cell kidney carcinoma cells as an example. According to the whole set of algorithms mentioned in Methods section, we calculate 7 potential esse