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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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A sample of switching mechanisms with two classes (shown by plus symbol and filled square).
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Figure 1: A sample of switching mechanisms with two classes (shown by plus symbol and filled square).

Mentions: Gene expression analysis is a basic and important technique in molecular biology. There are two typical and simple concepts for expression analysis: (i) differential expression, which examines the difference in expression for a single gene between different experimental conditions (classes), such as case and control patients (1), and (ii) coexpression, which focuses on a combination of multiple genes, checking whether they are over- or underexpressed simultaneously (2). One notion with both of these two properties is differential co-expression, in which coexpression patterns differ depending upon the experimental conditions (3,4). We address an issue of finding one type of differential coexpression, which hereafter we call a ‘switching mechanism’. The switching mechanism has two experimental conditions for expression of two genes, where two genes are positively correlated under one experimental condition while they are negatively correlated under the other condition (3,5–8). Figure 1 shows one simulated example of the switching mechanism. A simple, well-known case of the switching mechanism is Max, a transcription factor, which plays a role of an activator or a suppressor, depending on whether it binds to Myc (i.e. Myc-Max) or Mad (i.e. Mad-Max) (9). Another case is thyroid hormone receptor (TR), which forms a complex called TR-RXR and can be also an activator or a suppressor, depending on the absence or presence (amount) of thyroid hormone (10). Finding the switching mechanisms would be a key step to elucidating complex biological systems.Figure 1.


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

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

A sample of switching mechanisms with two classes (shown by plus symbol and filled square).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 1: A sample of switching mechanisms with two classes (shown by plus symbol and filled square).
Mentions: Gene expression analysis is a basic and important technique in molecular biology. There are two typical and simple concepts for expression analysis: (i) differential expression, which examines the difference in expression for a single gene between different experimental conditions (classes), such as case and control patients (1), and (ii) coexpression, which focuses on a combination of multiple genes, checking whether they are over- or underexpressed simultaneously (2). One notion with both of these two properties is differential co-expression, in which coexpression patterns differ depending upon the experimental conditions (3,4). We address an issue of finding one type of differential coexpression, which hereafter we call a ‘switching mechanism’. The switching mechanism has two experimental conditions for expression of two genes, where two genes are positively correlated under one experimental condition while they are negatively correlated under the other condition (3,5–8). Figure 1 shows one simulated example of the switching mechanism. A simple, well-known case of the switching mechanism is Max, a transcription factor, which plays a role of an activator or a suppressor, depending on whether it binds to Myc (i.e. Myc-Max) or Mad (i.e. Mad-Max) (9). Another case is thyroid hormone receptor (TR), which forms a complex called TR-RXR and can be also an activator or a suppressor, depending on the absence or presence (amount) of thyroid hormone (10). Finding the switching mechanisms would be a key step to elucidating complex biological systems.Figure 1.

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