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通过细胞网络方法预测表型相关基因:一个白色念珠菌感染的案例研究。

Prediction of phenotype-associated genes via a cellular network approach: a Candida albicans infection case study.

机构信息

Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu, Taiwan.

出版信息

PLoS One. 2012;7(4):e35339. doi: 10.1371/journal.pone.0035339. Epub 2012 Apr 11.

Abstract

Candida albicans is the most prevalent opportunistic fungal pathogen in humans causing superficial and serious systemic infections. The infection process can be divided into three stages: adhesion, invasion, and host cell damage. To enhance our understanding of these C. albicans infection stages, this study aimed to predict phenotype-associated genes involved during these three infection stages and their roles in C. albicans-host interactions. In light of the principles that proteins that lie closer to one another in a protein interaction network are more likely to have similar functions, and that genes regulated by the same transcription factors tend to have similar functions, a cellular network approach was proposed to predict the phenotype-associated genes in this study. A total of 4, 12, and 3 genes were predicted as adhesion-, invasion-, and damage-associated genes during C. albicans infection, respectively. These predicted genes highlight the facts that cell surface components are critical for cell adhesion, and that morphogenesis is crucial for cell invasion. In addition, they provide targets for further investigations into the mechanisms of the three C. albicans infection stages. These results give insights into the responses elicited in C. albicans during interaction with the host, possibly instrumental in identifying novel therapies to treat C. albicans infection.

摘要

白色念珠菌是人类中最常见的机会性真菌病原体,可引起浅表和严重的全身感染。感染过程可分为三个阶段:黏附、侵袭和宿主细胞损伤。为了增进我们对这些白色念珠菌感染阶段的理解,本研究旨在预测与这三个感染阶段相关的表型相关基因及其在白色念珠菌-宿主相互作用中的作用。鉴于蛋白质相互作用网络中彼此靠近的蛋白质更可能具有相似的功能的原则,以及受相同转录因子调控的基因往往具有相似的功能的原则,本研究提出了一种基于细胞网络的方法来预测与表型相关的基因。在白色念珠菌感染过程中,分别预测了 4、12 和 3 个基因作为黏附、侵袭和损伤相关基因。这些预测的基因突出了细胞表面成分对细胞黏附至关重要,形态发生对细胞侵袭至关重要的事实。此外,它们为进一步研究白色念珠菌感染的三个阶段的机制提供了目标。这些结果深入了解了白色念珠菌与宿主相互作用时引发的反应,可能有助于确定治疗白色念珠菌感染的新疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c4d/3324557/9f7dbc097af0/pone.0035339.g001.jpg

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