宿主與病原菌的交互作用與微生物所引起的感染是有高度相關的。研究宿主-病原菌的交互作用對於微生物學家、免疫學家以及其他的研究者是一個很重要的議題。白色念珠菌是一種相當常見的病原菌，它經常會在人體的表皮或是黏膜組織上與人類共生。另外，白色念珠菌會依據環境的情況而形成不同的形態。一般來說，白色念珠菌的菌絲型態所引起的致病性是最廣為研究的。
在這篇研究中，我們將集中在宿主組織被白色念珠菌感染情況下的細胞網路建構。利用模擬基因轉錄調控/蛋白質交互作用的動態方程與基因功能註解，一個整合性細胞網路結合了基因轉錄調控、蛋白質交互作用與細胞功能性。這個整合性細胞網路可以讓我們更了解白色念珠菌與宿主細胞發生作用時的一些生物機制。檢視這個網路的結構，我們在白色念珠菌感染宿主的過程發現了許多與重要的hub負責維持網路中的各個不同層面的元件通信，另外也發現許多與菌絲生長高度相關的信號傳遞路徑。最後再將對外界刺激產生反應的基因利用本身的功能做出適當的分類，以了解白色念珠菌在與宿主的作用的情況下會產生哪些相對應的反應來適應外界的刺激。
本篇研究提出了一個由上游信號傳遞路徑與下游基因調控網路整合而成的細胞網路，提供生物學家一個較完整的藍圖來研究白色念珠菌致病的機制。了解病原菌的生理機制對於藥物的研發與治療微生物疾病的策略運用是相當重要的，另一方面也能提供生物學家在研究宿主-病原菌相關研究上重要的參考。

The interaction between host and pathogen is highly connective with microbial infection. To investigate the host-pathogen interaction is an important topic for microbiologists, immunologists and other researchers. Candida albicans is the most prevalent opportunistic fungal pathogen as a commensal on the human skin and in mucous membranes. C. albicans can exist as in a variety of morphological forms.
In this study, we focus on constructing cellular network in relation to morphogenesis and virulence of infectious C. albicans on the host tissue. Based on the coupling gene regulation/protein interaction dynamic equation and functional gene annotation, an integrated cellular network is constructed to combine signal transduction pathway and gene regulatory network with cellular functionality of infectious C. albicans via database mining, time profile microarray and functional classification. The integrated cellular network provides insight into infection mechanisms of gene regulation and protein-protein interaction as well as cellular functions of C. albicans, during its interaction with the host cell. Fundamental understanding of such infection mechanisms is essential to the drug target development for sustainable prevention and control strategies for microbial infection and can further support all other research in host-pathogen interaction.

1 Introduction 1
2 Materials and Methods 7
2.1 Data selection and preprocessing 7
2.2 Candidate network construction via database mining 8
2.3 Dynamic model of integrated cellular network 9
2.4 Network parameter identification via time profile microarray data 13
2.6 Combination of gene regulatory network with signal transduction pathway 16
2.7 Analysis of Cellular functionality of downstream responsive genes 16
3 Results 17
3.1 Construction of integrated cellular network 17
3.2 The topology and highly connected hubs of integrated cellular network 20
3.3 Inspection of morphological switch-related signal transduction pathway 23
3.4 Cellular functionality classification of downstream responsive genes 27
4 Discussion 31
5 Conclusion 34
Bibliography 36

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