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ROS-DET: robust detector of switching mechanisms in gene expression.

Kayano M, Takigawa I, Shiga M, Tsuda K, Mamitsuka H - Nucleic Acids Res. (2011)

Bottom Line: Furthermore, for each of the top 10 pairs ranked by ROS-DET, we attempted to identify a pathway, i.e. consecutive biological phenomena, being related with the corresponding two genes by checking the biological literature.In 8 out of the 10 pairs, we found two parallel pathways, one of the two genes being in each of the two pathways and two pathways coming to (or starting with) the same gene.This indicates that two parallel pathways would be cooperatively used under one experimental condition, corresponding to the positive correlation, and the two pathways might be alternatively used under the other condition, corresponding to the negative correlation.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji 611-0011, Japan.

ABSTRACT
A switching mechanism in gene expression, where two genes are positively correlated in one condition and negatively correlated in the other condition, is a key to elucidating complex biological systems. There already exist methods for detecting switching mechanisms from microarrays. However, current approaches have problems under three real cases: outliers, expression values with a very small range and a small number of examples. ROS-DET overcomes these three problems, keeping the computational complexity of current approaches. We demonstrated that ROS-DET outperformed existing methods, under that all these three situations are considered. Furthermore, for each of the top 10 pairs ranked by ROS-DET, we attempted to identify a pathway, i.e. consecutive biological phenomena, being related with the corresponding two genes by checking the biological literature. In 8 out of the 10 pairs, we found two parallel pathways, one of the two genes being in each of the two pathways and two pathways coming to (or starting with) the same gene. This indicates that two parallel pathways would be cooperatively used under one experimental condition, corresponding to the positive correlation, and the two pathways might be alternatively used under the other condition, corresponding to the negative correlation. ROS-DET is available from http://www.bic.kyoto-u.ac.jp/pathway/kayano/ros-det.htm.

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Pathways for the top ranked gene pair.
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Figure 9: Pathways for the top ranked gene pair.

Mentions: Figure 9 summarizes these genes into two parallel pathways which both go to TP53. This figure shows a direct implication to the mechanism between EID1 and USP4 (or USP7), being consistent with parallel pathways. Two conditions of GDS2656 are fetal and adult. Figure 6a shows that two genes are positively correlated under fetal while negatively correlated under adult, implying that TP53 might be alternatively regulated by NSMCE4A and USP4 under adult, while TP53 could be regulated in a cooperative manner under fetal. To confirm this finding, we attempted to check the expression of TP53 but we could not find TP53 in GDS2656, and so instead we checked the expression of TP53RK, a TP53 regulating kinase. Table 2 shows the biweight midcorrelation between TP53RK and each of two genes of the top ranked pair. The result shows that TP53RK is positively correlated with both NSMCE4A and USP4 under fetal, while under adult, TP53RK is positively and negatively correlated with NSMCE4A and USP4, respectively. This result is consistent with our finding, which implies cooperative regulation under fetal and alternative regulation under adult.Figure 9.


ROS-DET: robust detector of switching mechanisms in gene expression.

Kayano M, Takigawa I, Shiga M, Tsuda K, Mamitsuka H - Nucleic Acids Res. (2011)

Pathways for the top ranked gene pair.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3113587&req=5

Figure 9: Pathways for the top ranked gene pair.
Mentions: Figure 9 summarizes these genes into two parallel pathways which both go to TP53. This figure shows a direct implication to the mechanism between EID1 and USP4 (or USP7), being consistent with parallel pathways. Two conditions of GDS2656 are fetal and adult. Figure 6a shows that two genes are positively correlated under fetal while negatively correlated under adult, implying that TP53 might be alternatively regulated by NSMCE4A and USP4 under adult, while TP53 could be regulated in a cooperative manner under fetal. To confirm this finding, we attempted to check the expression of TP53 but we could not find TP53 in GDS2656, and so instead we checked the expression of TP53RK, a TP53 regulating kinase. Table 2 shows the biweight midcorrelation between TP53RK and each of two genes of the top ranked pair. The result shows that TP53RK is positively correlated with both NSMCE4A and USP4 under fetal, while under adult, TP53RK is positively and negatively correlated with NSMCE4A and USP4, respectively. This result is consistent with our finding, which implies cooperative regulation under fetal and alternative regulation under adult.Figure 9.

Bottom Line: Furthermore, for each of the top 10 pairs ranked by ROS-DET, we attempted to identify a pathway, i.e. consecutive biological phenomena, being related with the corresponding two genes by checking the biological literature.In 8 out of the 10 pairs, we found two parallel pathways, one of the two genes being in each of the two pathways and two pathways coming to (or starting with) the same gene.This indicates that two parallel pathways would be cooperatively used under one experimental condition, corresponding to the positive correlation, and the two pathways might be alternatively used under the other condition, corresponding to the negative correlation.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji 611-0011, Japan.

ABSTRACT
A switching mechanism in gene expression, where two genes are positively correlated in one condition and negatively correlated in the other condition, is a key to elucidating complex biological systems. There already exist methods for detecting switching mechanisms from microarrays. However, current approaches have problems under three real cases: outliers, expression values with a very small range and a small number of examples. ROS-DET overcomes these three problems, keeping the computational complexity of current approaches. We demonstrated that ROS-DET outperformed existing methods, under that all these three situations are considered. Furthermore, for each of the top 10 pairs ranked by ROS-DET, we attempted to identify a pathway, i.e. consecutive biological phenomena, being related with the corresponding two genes by checking the biological literature. In 8 out of the 10 pairs, we found two parallel pathways, one of the two genes being in each of the two pathways and two pathways coming to (or starting with) the same gene. This indicates that two parallel pathways would be cooperatively used under one experimental condition, corresponding to the positive correlation, and the two pathways might be alternatively used under the other condition, corresponding to the negative correlation. ROS-DET is available from http://www.bic.kyoto-u.ac.jp/pathway/kayano/ros-det.htm.

Show MeSH