Gene Expression Profiling with Survival Analysis on Microarray Data

如何藉由DNA微陣列資料跟存活資料的資訊來找出基因表現定型一直是個重要的議題。這些研究的主要目標是從大量的基因中找出那些真正跟存活時間或其它重要的臨床結果有顯著關係的小部分。Threshold Gradient Directed Regularization (TGDR)是ㄧ種已經被應用在高維度迴歸問題中能同時處理變數選取以及模型配適的演算法。然而，TGDR採用一種梯度投影型態的演算法使得收斂速率緩慢。在本篇論文中，我們建議新的包含Newton-Raphson求解演算法類型的改良版TGDR方法。我們建議的方法有類似TGDR的特性但卻有比較快的收斂速率。文中並利用一筆附有設限存活時間的真實微陣列癌症資料來做示範。 本篇論文的第二部份是關於適用於區間設限存活資料的重複抽樣Peto-Peto檢定。這個重複抽樣Peto-Peto檢定能夠評估存活函數估計方法的檢定力，例如Turnbull的估計方法以及Kaplan-Meier的估計方法。這個檢定方法顯示出在區間設限資料時Kaplan-Meier的估計方法的檢定力要比Turnbull的估計方法的檢定力來得低。這個檢定方法將以模擬的區間設限資料以及一筆真實關於乳癌研究的區間設限資料來說明。Analyzing censored survival data with high-dimensional covariates arising from the microarray data has been an important issue. The main goal is to find genes that have pivotal influence with patient's survival time or other important clinical outcomes. Threshold Gradient Directed Regularization (TGDR) method has been used for simultaneous variable selection and model building in high-dimensional regression problems. However, the TGDR method adopts a gradient-projection type of method and would have slow convergence rate. In this thesis, we proposed Modified TGDR algorithms which incorporate Newton-Raphson type of search algorithm. Our proposed approaches have the similar characteristics with TGDR but faster convergence rates. A real cancer microarray data with censored survival times is used for demonstration. The second part of this thesis is about a proposed resampling based Peto-Peto test for survival functions on interval censored data. The proposed resampling based Peto-Peto test can evaluate the power of survival function estimation methods, such as Turnbull’s Procedure and Kaplan-Meier estimate. The test shows that the power based on Kaplan-Meier estimate is lower than that based on Turnbull’s estimation on interval censored data. This proposed test is demonstrated on simulated data and a real interval censored data from a breast cancer study