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一種基于仿真的預測癌細胞致死基因的方法

Prediction for the essential genes in cancer cells based on simulation

作者: 許揚  鄭浩然 
單位:中國科學技術大學計算機科學與技術學院(合肥230027)
關鍵詞: 約束建模;基因敲除;特異網(wǎng)絡;致死基因;腎透明細胞癌 
分類號:R318
出版年·卷·期(頁碼):2017·36·6(591-596)
摘要:

目的 癌細胞致死基因的研究是治療癌癥的重要嘗試,其發(fā)現(xiàn)依賴于生物學上的基因敲除實驗。鑒于此類實驗的高代價、長周期等不足,本文給出一種基于計算機仿真的預測癌細胞致死基因的方法,旨在運用計算機仿真技術預測對癌細胞研究有價值的信息,為基因敲除的生物實驗提供線索,幫助降低實驗成本。方法 計算機仿真實驗基于人類全基因組代謝網(wǎng)絡,融合癌細胞的基因表達數(shù)據(jù),用一種基于約束建模的方法,以預測癌細胞代謝網(wǎng)絡中有活性的反應,并將這些反應命名為“core reactions”,將“core reactions”作為輸入,重構出一致的癌癥工作網(wǎng)絡。在該網(wǎng)絡上,使用基于約束的流量平衡基因敲除算法,獲取使得工作網(wǎng)絡biomass產(chǎn)量為0的基因,即致死基因。結(jié)果 以腎透明細胞癌為例,根據(jù)上述算法,計算結(jié)果給出了腎透明細胞癌潛在的7個致死基因。結(jié)論 本文給出一種高通量數(shù)據(jù)結(jié)合代謝網(wǎng)絡,構造癌癥特異網(wǎng)絡,并通過計算機仿真基因敲除以獲取癌細胞致死基因的方法。此方法通用、高效,有助于更好地開展生物學實驗。

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 metabolic network.Integrating the transcriptomics data of cancer cells,we use a mathematic model to predict the “core reactions” of cancer 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 balance analysis(FBA) knockout algorithm.Results 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 essential genes.Conclusions This work proposes a simulation based method which connects transcriptomics data and metabolic network to create a cancer specific network to study on essential genes of cancer cells.The method is universal and efficient, and helpful to make wet experiments better.

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