利用時間序列之微陣列基因表現資料來比較人類和老鼠在心臟胚胎發育的關係

Abstract

心臟的發育是非常複雜的一個生理機制，有非常多的基因在心臟胚胎發育過程參與其細胞調控並決定了心臟的形成。微陣列（基因晶片）的實驗能夠一次大量產生許多基因表現的數據，在此研究中，想利用此一技術產生關於心臟發育時期的基因表現值。由於相關法令的問題，人類心臟胚胎的檢體獲取非常不易。為了更了解關於心臟發育的機制，故也利用老鼠心臟發育的胚胎來建立一個人類和老鼠的在心臟發育方面時間序列的平台。目前大部分的研究人員都使用一種物種來研究發育時期基因的變化，我們特別利用人類與老鼠心臟發育胚胎的時間序列檢體，並且使用兩物種間的同源基因和dynamic time warping演算法將此兩種物種作同源基因的分析，找出人類和老鼠中同源基因有相似變化的基因。而後再利用這些基因，做進一步的系統化分析，探討其功能和交互關係。此研究目的就是希望能利用基因表現的數據來更了解心臟發育過程中基因表現的模式與變化，並希望能發掘尚未被先前研究所探討的發育調控基因。

Heart development is a complex process involving many genes which control cell behavior in the embryo and determine its pattern, its form, and much of its behavior. Microarray experiments can generate an enormous amount of data at one time, so we use this technology to obtain gene expression profiles in heart embryonic development. But it is usually very difficult to obtain human heart fetus sample because of the issues of ethical, legal, and social consideration. In order to help us get more understanding of human heart development, we can use the mouse model system that is most often used. Therefore, we must establish a mapping system to make a cross bridge between these two species on developmental stages. To date, the vast majority of researches have focused their study on one species. Specially, we utilize orthologous genes and incorporate the dynamic time warping algorithm in order to map the time points that human and mouse gene expression profiles having highly correlated pattern. Firstly, we apply the algorithm to select the best time-warped orthologous genes having similar pattern. Then, these genes are clustered into groups. Each group has its unique mapping pattern and different biological meaning. The following task is to find relationship and pattern in distinct groups of genes, and to get close understanding into molecular process and gene function, mechanisms of embryogenesis of the heart, and comparative genomics. Ultimately, our aim is to achieve new insights into the heart developmental biology.