Clustering of Human Gene Expression Stimulated by Bacterial Infection from Microarray Analysis

Panthong Kulsantiwong, Phanarut Srichetta, Wannasiri Thurachon
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Abstract

Gene expression profiling of human cells against bacterial infection has become a major tool that allows explaining genome-wide expression changes in health and disease, which is important for the diagnosis and prognosis of diseases. A good way to identify human genes with similar biological activities or functions when stimulated by bacteria injection is by clustering. The objective of this research is to cluster human gene expression stimulated by wide-type (WS) and mutant strain (MS) of Burkholderia pseudomallei compared to controls via microarray transcriptional profile. K-means clustering algorithm was used to cluster human gene expression based on the fold change (FC) values of primary human monocytes (PHM) stimulated by both strains. In the phase of determining k-cluster experimented on PHM genes stimulated with WS, with MS and without strains stimulation (control), it results were 7, 7 and 7 clusters, respectively. According to three clustering patterns based on bacterial strain of stimulation, genes in cluster in the same ranked level reveals the similar molecular functions whereas different levels have different functions. Moreover, the clusters with highest FC values are also crucial. In the first top cluster, gene expression in PHM stimulated with WS and MS compared to the control, the cytokine genes especially csf2, csf3, il23A, il6 and stat4 were found in all bacterial stimulation. These gene clusters showed the molecular functions in PHM including cytokine activity, growth receptor binding, growth factor activity and cytokine receptor binding. These results indicated that the cluster of human genes infected by B. pseudomallei revealed the association between immune response genes and their molecular functions. These clusters of PHM genes might be the important biomarker genes which related for understanding the human immune response against B. pseudomallei infection and prognosis the melioidosis patients.
细菌感染刺激人类基因表达的微阵列分析
人类细胞抗细菌感染的基因表达谱已成为解释健康和疾病中全基因组表达变化的重要工具,对疾病的诊断和预后具有重要意义。在细菌注射刺激下,识别具有相似生物活性或功能的人类基因是一种很好的方法。本研究的目的是通过微阵列转录谱,将伪氏伯克霍尔德氏菌宽型(WS)和突变株(MS)刺激的人类基因表达与对照进行聚类。采用K-means聚类算法,根据两株菌株刺激的原代人单核细胞(PHM)的fold change (FC)值对人基因表达进行聚类。在确定k-簇的阶段,对WS、MS和无菌株刺激(对照)的PHM基因进行实验,结果分别为7个、7个和7个簇。根据三种基于刺激菌株的聚类模式,同一等级水平的聚类基因显示出相似的分子功能,而不同等级的聚类基因显示出不同的功能。此外,具有最高FC值的集群也是至关重要的。在顶部的第一个簇中,与对照组相比,WS和MS刺激的PHM中的基因表达,细胞因子基因特别是csf2, csf3, il23A, il6和stat4在所有细菌刺激中都被发现。这些基因簇在PHM中的分子功能包括细胞因子活性、生长受体结合、生长因子活性和细胞因子受体结合。这些结果表明,假芽孢杆菌感染的人类基因簇揭示了免疫应答基因与其分子功能之间的关联。这些PHM基因簇可能是了解人类对假芽孢杆菌感染的免疫反应和类鼻疽患者预后相关的重要生物标记基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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