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A systems biology approach to construct the gene regulatory network of systemic inflammation via microarray and databases mining.

Chen BS, Yang SK, Lan CY, Chuang YJ - BMC Med Genomics (2008)

Bottom Line: When primary pathogenetic events remains unclear due to its immense complexity, construction and analysis of the gene regulatory network of inflammation at times becomes the best way to understand the detrimental effects of disease.In this study, Data mining and dynamic network analyses were integrated to examine the gene regulatory network in the inflammatory response system.Compared with previous methodologies reported in the literatures, the proposed gene network perturbation method has shown a great improvement in analyzing the systemic inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Lab of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu, 300, Taiwan. bschen@ee.nthu.edu.tw.

ABSTRACT

Background: Inflammation is a hallmark of many human diseases. Elucidating the mechanisms underlying systemic inflammation has long been an important topic in basic and clinical research. When primary pathogenetic events remains unclear due to its immense complexity, construction and analysis of the gene regulatory network of inflammation at times becomes the best way to understand the detrimental effects of disease. However, it is difficult to recognize and evaluate relevant biological processes from the huge quantities of experimental data. It is hence appealing to find an algorithm which can generate a gene regulatory network of systemic inflammation from high-throughput genomic studies of human diseases. Such network will be essential for us to extract valuable information from the complex and chaotic network under diseased conditions.

Results: In this study, we construct a gene regulatory network of inflammation using data extracted from the Ensembl and JASPAR databases. We also integrate and apply a number of systematic algorithms like cross correlation threshold, maximum likelihood estimation method and Akaike Information Criterion (AIC) on time-lapsed microarray data to refine the genome-wide transcriptional regulatory network in response to bacterial endotoxins in the context of dynamic activated genes, which are regulated by transcription factors (TFs) such as NF-kappaB. This systematic approach is used to investigate the stochastic interaction represented by the dynamic leukocyte gene expression profiles of human subject exposed to an inflammatory stimulus (bacterial endotoxin). Based on the kinetic parameters of the dynamic gene regulatory network, we identify important properties (such as susceptibility to infection) of the immune system, which may be useful for translational research. Finally, robustness of the inflammatory gene network is also inferred by analyzing the hubs and "weak ties" structures of the gene network.

Conclusion: In this study, Data mining and dynamic network analyses were integrated to examine the gene regulatory network in the inflammatory response system. Compared with previous methodologies reported in the literatures, the proposed gene network perturbation method has shown a great improvement in analyzing the systemic inflammation.

No MeSH data available.


Related in: MedlinePlus

The important proinflammatory gene network induced or activated by NF-κB in immune system without LPS. The important proinflammatory gene network in normal condition.
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Figure 8: The important proinflammatory gene network induced or activated by NF-κB in immune system without LPS. The important proinflammatory gene network in normal condition.

Mentions: The NF-κB pathway, which is an important modular inflammatory system, is illustrated as a trimmed down gene regulatory network depicted in Figure 7 and 8. This concise network includes important proinflammatory cytokine genes: IL1A, IL1B, IL1R, IL6, TNFA, IL17, IL8 and the receptor genes IL1R, TLR4 and TNFR, all of which have well-known roles in the NF-κB signaling pathway. This concise network can help us to monitor the performance of inflammatory responses under diverse conditions. By the proposed method shown in this study, we can predict the dynamic profiles of those cytokines. As expected, our results are comparable to the findings published in previous studies [8,24] discussed in the following paragraphs. Our in silico findings confirm the wet-bench observation that many characterized genes in the common inflammation response are regulated by the transcription factor NF-κB [6].


A systems biology approach to construct the gene regulatory network of systemic inflammation via microarray and databases mining.

Chen BS, Yang SK, Lan CY, Chuang YJ - BMC Med Genomics (2008)

The important proinflammatory gene network induced or activated by NF-κB in immune system without LPS. The important proinflammatory gene network in normal condition.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2567339&req=5

Figure 8: The important proinflammatory gene network induced or activated by NF-κB in immune system without LPS. The important proinflammatory gene network in normal condition.
Mentions: The NF-κB pathway, which is an important modular inflammatory system, is illustrated as a trimmed down gene regulatory network depicted in Figure 7 and 8. This concise network includes important proinflammatory cytokine genes: IL1A, IL1B, IL1R, IL6, TNFA, IL17, IL8 and the receptor genes IL1R, TLR4 and TNFR, all of which have well-known roles in the NF-κB signaling pathway. This concise network can help us to monitor the performance of inflammatory responses under diverse conditions. By the proposed method shown in this study, we can predict the dynamic profiles of those cytokines. As expected, our results are comparable to the findings published in previous studies [8,24] discussed in the following paragraphs. Our in silico findings confirm the wet-bench observation that many characterized genes in the common inflammation response are regulated by the transcription factor NF-κB [6].

Bottom Line: When primary pathogenetic events remains unclear due to its immense complexity, construction and analysis of the gene regulatory network of inflammation at times becomes the best way to understand the detrimental effects of disease.In this study, Data mining and dynamic network analyses were integrated to examine the gene regulatory network in the inflammatory response system.Compared with previous methodologies reported in the literatures, the proposed gene network perturbation method has shown a great improvement in analyzing the systemic inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Lab of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu, 300, Taiwan. bschen@ee.nthu.edu.tw.

ABSTRACT

Background: Inflammation is a hallmark of many human diseases. Elucidating the mechanisms underlying systemic inflammation has long been an important topic in basic and clinical research. When primary pathogenetic events remains unclear due to its immense complexity, construction and analysis of the gene regulatory network of inflammation at times becomes the best way to understand the detrimental effects of disease. However, it is difficult to recognize and evaluate relevant biological processes from the huge quantities of experimental data. It is hence appealing to find an algorithm which can generate a gene regulatory network of systemic inflammation from high-throughput genomic studies of human diseases. Such network will be essential for us to extract valuable information from the complex and chaotic network under diseased conditions.

Results: In this study, we construct a gene regulatory network of inflammation using data extracted from the Ensembl and JASPAR databases. We also integrate and apply a number of systematic algorithms like cross correlation threshold, maximum likelihood estimation method and Akaike Information Criterion (AIC) on time-lapsed microarray data to refine the genome-wide transcriptional regulatory network in response to bacterial endotoxins in the context of dynamic activated genes, which are regulated by transcription factors (TFs) such as NF-kappaB. This systematic approach is used to investigate the stochastic interaction represented by the dynamic leukocyte gene expression profiles of human subject exposed to an inflammatory stimulus (bacterial endotoxin). Based on the kinetic parameters of the dynamic gene regulatory network, we identify important properties (such as susceptibility to infection) of the immune system, which may be useful for translational research. Finally, robustness of the inflammatory gene network is also inferred by analyzing the hubs and "weak ties" structures of the gene network.

Conclusion: In this study, Data mining and dynamic network analyses were integrated to examine the gene regulatory network in the inflammatory response system. Compared with previous methodologies reported in the literatures, the proposed gene network perturbation method has shown a great improvement in analyzing the systemic inflammation.

No MeSH data available.


Related in: MedlinePlus