以遺傳演算法解標靶藥物組合最佳化與生物晶片集群分析之特徵篩選最佳化

組合最佳化問題是機器學習的非常重要課題，眾多自然科學、工程以及生物資訊領域的問題都可轉換成為組合最佳化的問題；相關維度趨高的實務難題，顯示慣用的暴力搜尋法通常不具實際效用。本篇論文設計實作遺傳演算法的程式架構GAPF，期望達成具有大量組合元素與不固定選取數量相關組合最佳化問題的演算解題。本法GAPF已經應用於生物資訊相關藥物組合設計與特徵篩選的問題類型，並初步成功獲得良好成果；對於生物晶片資料分析問題類型，GAPF迅速挑選可能關鍵基因(influential genes)，達成階層式分群(hierarchical clustering)的接近最佳解；對於藥物組合限定設計問題類型，設計同時考慮多種藥物相關多重基因途徑(genetic pathway)的正作用與副作用的適應函數(fitness function)，並利用GAPF得到限定數量的藥物下效果最佳之藥物組合。

關鍵字

組合最佳化；特徵篩選；關鍵基因；組合藥物設計；抗癌藥物

並列摘要

Combinatorial optimization is an important topic on finding an optimal set of objects from a finite set of objects in applied mathematics and theoretical computer science. Various problems in science, engineering, and bioinformatics may be described as within such category. In cases with large dimensionality, the exhaustive search method is often too slow to be of any practical usage. This thesis implements a Genetic Algorithm Programming Framework (GAPF) for solving combinatorial optimization problems with large dimensionality and with an uncertain or assigned amount of selection. GAPF is applied to practical bioinformatics problems including drug combination discovery and influential gene discovery. On microarray data analysis, the hierarchical cluster analysis of the resulting gene profile from GAPF shows a near optimal separation when compared with the original T-Test results. On targeted drug combination design, we designed a fitness function which considers multiple drugs against multiple genetic pathways with positive and side effects. GAPF results in solutions with minimum drugs usage and maximum pathway coverage.

並列關鍵字

combinatorial optimization ； feature selection ； influential genes ； drug combination design ； anticancer drug

參考文獻

Al-Shahrour, F., et al. (2007) FatiGO +: a functional profiling tool for genomic data. Integration of functional annotation, regulatory motifs and interaction data with microarray experiments, Nucleic Acids Res, 35, W91-96.

Almuallim, H. and Dietterich, T.G. (1991) Learning with many irrelevant features. Proceedings of the Ninth National Conference on Artificial Intelligence (AAAI-91). AAAI Press, pp. 547-552.

Benkert, O., Grunder, G. and Wetzel, H. (1992) Dopamine autoreceptor agonists in the treatment of schizophrenia and major depression, Pharmacopsychiatry, 25, 254-260.

Bernard, R., et al. (2010) Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression, Mol Psychiatry.

Berrettini, W. (2003) Bipolar disorder and schizophrenia: not so distant relatives?, World Psychiatry, 2, 68-72.

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以遺傳演算法解標靶藥物組合最佳化與生物晶片集群分析之特徵篩選最佳化

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