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Robustness analysis on interspecies interaction network for iron and glucose competition between Candida albicans and zebrafish during infection.

Lin C, Lin CN, Wang YC, Liu FY, Chien YW, Chuang YJ, Lan CY, Hsieh WP, Chen BS - BMC Syst Biol (2014)

Bottom Line: Candida albicans has emerged as an important model organism for the study of infectious disease.The behaviors of the highly connected or differentially regulated proteins identified from the resulting networks were further investigated. “Robustness” is an important system property that measures the ability of the system tolerating the intrinsic perturbations in a dynamic network.Moreover, the networks also assist in elucidating the offensive and defensive mechanisms of C. albicans and zebrafish during their competition for iron and glucose.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
Candida albicans has emerged as an important model organism for the study of infectious disease. Using high-throughput simultaneously quantified time-course transcriptomics, this study constructed host-pathogen interspecies interaction networks between C. albicans and zebrafish during the adhesion, invasion, and damage stages. Given that iron and glucose have been identified as crucial resources required during the infection process between C. albicans and zebrafish, we focused on the construction of the interspecies networks associated with them. Furthermore, a randomization technique was proposed to identify differentially regulated proteins that are statistically eminent for the three infection stages. The behaviors of the highly connected or differentially regulated proteins identified from the resulting networks were further investigated. “Robustness” is an important system property that measures the ability of the system tolerating the intrinsic perturbations in a dynamic network. This characteristic provides a systematic and quantitative view to elucidate the dynamics of iron and glucose competition in terms of the interspecies interaction networks. Here, we further estimated the robustness of our constructed interspecies interaction networks for the three infection stages. The constructed networks and robustness analysis provided significant insight into dynamic interactions related to iron and glucose competition during infection and enabled us to quantify the system’s intrinsic perturbation tolerance ability during iron and glucose competition throughout the three infection stages. Moreover, the networks also assist in elucidating the offensive and defensive mechanisms of C. albicans and zebrafish during their competition for iron and glucose. Our proposed method can be easily extended to identify other such networks involved in the competition for essential resources during infection.

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Heatmap of Zebrafish glucose-related immune proteins with statistically significant interactions in the adhesion stage. The heatmap of the listed proteins in table 5 shows the expression levels of the time-course microarray data with nine times.
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Figure 5: Heatmap of Zebrafish glucose-related immune proteins with statistically significant interactions in the adhesion stage. The heatmap of the listed proteins in table 5 shows the expression levels of the time-course microarray data with nine times.

Mentions: Based on the host-pathogen interaction network constructed above, we were able to obtain the number of linkages of each target protein in zebrafish and the corresponding interspecies interaction proteins in C. albicans during the three infection stages, identifying important hub proteins in both species (see Additional file 1.xlsx in supplementary file for details). To further identify the target proteins and interspecies interaction proteins that had statistically significant roles during each of the three infection stages, we randomized our simultaneously quantified time-course microarray data with respect to time-points. It should be noted that since zebrafish proteins were set as targets for interspecies interaction, this randomization was only applied to zebrafish and not to C. albicans data. Microarray data of zebrafish target immune proteins in the iron-related and glucose-related pool were each randomized 10,000 times. Interspecies interaction networks were constructed and the number of linkages of each protein recorded in each run, yielding the distribution of the number of linkages for each protein in the three infection stages. A protein was determined to be statistically significant in the corresponding stage if its original number of linkages was located closer to the low-probability area rather than the mean at a significance level of p < 0.05 with Student's t-test. Zebrafish target proteins or C. albicans interspecies interaction proteins were determined to be statistically significant for each of the three infection stages (see Table 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 for the complete lists and Figure 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 for the corresponding heatmap. See Additional file 2.zip for the original heatmap).


Robustness analysis on interspecies interaction network for iron and glucose competition between Candida albicans and zebrafish during infection.

Lin C, Lin CN, Wang YC, Liu FY, Chien YW, Chuang YJ, Lan CY, Hsieh WP, Chen BS - BMC Syst Biol (2014)

Heatmap of Zebrafish glucose-related immune proteins with statistically significant interactions in the adhesion stage. The heatmap of the listed proteins in table 5 shows the expression levels of the time-course microarray data with nine times.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4305985&req=5

Figure 5: Heatmap of Zebrafish glucose-related immune proteins with statistically significant interactions in the adhesion stage. The heatmap of the listed proteins in table 5 shows the expression levels of the time-course microarray data with nine times.
Mentions: Based on the host-pathogen interaction network constructed above, we were able to obtain the number of linkages of each target protein in zebrafish and the corresponding interspecies interaction proteins in C. albicans during the three infection stages, identifying important hub proteins in both species (see Additional file 1.xlsx in supplementary file for details). To further identify the target proteins and interspecies interaction proteins that had statistically significant roles during each of the three infection stages, we randomized our simultaneously quantified time-course microarray data with respect to time-points. It should be noted that since zebrafish proteins were set as targets for interspecies interaction, this randomization was only applied to zebrafish and not to C. albicans data. Microarray data of zebrafish target immune proteins in the iron-related and glucose-related pool were each randomized 10,000 times. Interspecies interaction networks were constructed and the number of linkages of each protein recorded in each run, yielding the distribution of the number of linkages for each protein in the three infection stages. A protein was determined to be statistically significant in the corresponding stage if its original number of linkages was located closer to the low-probability area rather than the mean at a significance level of p < 0.05 with Student's t-test. Zebrafish target proteins or C. albicans interspecies interaction proteins were determined to be statistically significant for each of the three infection stages (see Table 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 for the complete lists and Figure 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 for the corresponding heatmap. See Additional file 2.zip for the original heatmap).

Bottom Line: Candida albicans has emerged as an important model organism for the study of infectious disease.The behaviors of the highly connected or differentially regulated proteins identified from the resulting networks were further investigated. “Robustness” is an important system property that measures the ability of the system tolerating the intrinsic perturbations in a dynamic network.Moreover, the networks also assist in elucidating the offensive and defensive mechanisms of C. albicans and zebrafish during their competition for iron and glucose.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
Candida albicans has emerged as an important model organism for the study of infectious disease. Using high-throughput simultaneously quantified time-course transcriptomics, this study constructed host-pathogen interspecies interaction networks between C. albicans and zebrafish during the adhesion, invasion, and damage stages. Given that iron and glucose have been identified as crucial resources required during the infection process between C. albicans and zebrafish, we focused on the construction of the interspecies networks associated with them. Furthermore, a randomization technique was proposed to identify differentially regulated proteins that are statistically eminent for the three infection stages. The behaviors of the highly connected or differentially regulated proteins identified from the resulting networks were further investigated. “Robustness” is an important system property that measures the ability of the system tolerating the intrinsic perturbations in a dynamic network. This characteristic provides a systematic and quantitative view to elucidate the dynamics of iron and glucose competition in terms of the interspecies interaction networks. Here, we further estimated the robustness of our constructed interspecies interaction networks for the three infection stages. The constructed networks and robustness analysis provided significant insight into dynamic interactions related to iron and glucose competition during infection and enabled us to quantify the system’s intrinsic perturbation tolerance ability during iron and glucose competition throughout the three infection stages. Moreover, the networks also assist in elucidating the offensive and defensive mechanisms of C. albicans and zebrafish during their competition for iron and glucose. Our proposed method can be easily extended to identify other such networks involved in the competition for essential resources during infection.

Show MeSH
Related in: MedlinePlus