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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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Expression values of the top 10 gene pairs in the output of WCOR for real data.
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Figure 5: Expression values of the top 10 gene pairs in the output of WCOR for real data.

Mentions: Figure 5 shows expression values under two experimental conditions (• and +) of the top 10 gene pairs in the output of WCOR. This figure reveals that the number of examples was very small for any gene pair, by which some pairs cannot necessarily be switching mechanisms. For example, the eighth ranked pair consisted of three distant islands, which could not have been a switching mechanisms, and the 10th ranked pair had two non-overlapped distributions which also could not have been a switching mechanism. On the other hand, Figure 6 shows the top 10 gene pairs in the output of ECOR. Each distribution of Figure 6 can be seen as a switching mechanism more clearly than those of Figure 5. This result indicates that the outputs of WCOR were likely to be the cases with the smaller number of examples, and ECOR works for removing dubious cases in the outputs of WCOR.Figure 5.


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

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

Expression values of the top 10 gene pairs in the output of WCOR for real data.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 5: Expression values of the top 10 gene pairs in the output of WCOR for real data.
Mentions: Figure 5 shows expression values under two experimental conditions (• and +) of the top 10 gene pairs in the output of WCOR. This figure reveals that the number of examples was very small for any gene pair, by which some pairs cannot necessarily be switching mechanisms. For example, the eighth ranked pair consisted of three distant islands, which could not have been a switching mechanisms, and the 10th ranked pair had two non-overlapped distributions which also could not have been a switching mechanism. On the other hand, Figure 6 shows the top 10 gene pairs in the output of ECOR. Each distribution of Figure 6 can be seen as a switching mechanism more clearly than those of Figure 5. This result indicates that the outputs of WCOR were likely to be the cases with the smaller number of examples, and ECOR works for removing dubious cases in the outputs of WCOR.Figure 5.

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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