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. 2008 Mar 19;3(3):e1821.
doi: 10.1371/journal.pone.0001821.

Identification of direct target genes using joint sequence and expression likelihood with application to DAF-16

Ron X Yu  1 , Jie Liu, Nick True, Wei Wang
Affiliations

Identification of direct target genes using joint sequence and expression likelihood with application to DAF-16

Ron X Yu et al. PLoS One. .

Abstract

A major challenge in the post-genome era is to reconstruct regulatory networks from the biological knowledge accumulated up to date. The development of tools for identifying direct target genes of transcription factors (TFs) is critical to this endeavor. Given a set of microarray experiments, a probabilistic model called TRANSMODIS has been developed which can infer the direct targets of a TF by integrating sequence motif, gene expression and ChIP-chip data. The performance of TRANSMODIS was first validated on a set of transcription factor perturbation experiments (TFPEs) involving Pho4p, a well studied TF in Saccharomyces cerevisiae. TRANSMODIS removed elements of arbitrariness in manual target gene selection process and produced results that concur with one's intuition. TRANSMODIS was further validated on a genome-wide scale by comparing it with two other methods in Saccharomyces cerevisiae. The usefulness of TRANSMODIS was then demonstrated by applying it to the identification of direct targets of DAF-16, a critical TF regulating ageing in Caenorhabditis elegans. We found that 189 genes were tightly regulated by DAF-16. In addition, DAF-16 has differential preference for motifs when acting as an activator or repressor, which awaits experimental verification. TRANSMODIS is computationally efficient and robust, making it a useful probabilistic framework for finding immediate targets.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Comparison between the expression profiles of PHO81 and its two homologs SPL2 and YPL110C in the eight TFPE experiments of Pho4p.
Red and green colors represent up- and down-regulation, respectively. The brightness of the color is proportional to the absolute expression ratio.
Figure 2
Figure 2. Expression profiles of class 1 and class 2 direct targets of DAF-16 in Caenorhabditis elegans identified by TRANSMODIS.
Figure 3
Figure 3. Enriched motifs in the class 1 and class 2 target genes of DAF-16.
The x axis is the position and the y axis is the log2 ratio between the target and non-target weight matrices.
See this image and copyright information in PMC

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