Construction of predictive promoter models on the example of antibacterial response of human epithelial cells

Ekaterina Shelest,Edgar Wingender

doi:10.1186/1742-4682-2-2

Abstract

BackgroundBinding of a bacteria to a eukaryotic cell triggers a complex network of interactions in and between both cells. P. aeruginosa is a pathogen that causes acute and chronic lung infections by interacting with the pulmonary epithelial cells. We use this example for examining the ways of triggering the response of the eukaryotic cell(s), leading us to a better understanding of the details of the inflammatory process in general.ResultsConsidering a set of genes co-expressed during the antibacterial response of human lung epithelial cells, we constructed a promoter model for the search of additional target genes potentially involved in the same cell response. The model construction is based on the consideration of pair-wise combinations of transcription factor binding sites (TFBS).It has been shown that the antibacterial response of human epithelial cells is triggered by at least two distinct pathways. We therefore supposed that there are two subsets of promoters activated by each of them. Optimally, they should be "complementary" in the sense of appearing in complementary subsets of the (+)-training set. We developed the concept of complementary pairs, i.e., two mutually exclusive pairs of TFBS, each of which should be found in one of the two complementary subsets.ConclusionsWe suggest a simple, but exhaustive method for searching for TFBS pairs which characterize the whole (+)-training set, as well as for complementary pairs. Applying this method, we came up with a promoter model of antibacterial response genes that consists of one TFBS pair which should be found in the whole training set and four complementary pairs.We applied this model to screening of 13,000 upstream regions of human genes and identified 430 new target genes which are potentially involved in antibacterial defense mechanisms.

Highlights

Binding of a bacteria to a eukaryotic cell triggers a complex network of interactions in and between both cells
We came up with a promoter model of antibacterial response genes that consists of one transcription factor binding sites (TFBS) pair which should be found in the whole training set and four complementary pairs
The overwhelming majority of methods and tools estimating the relevance of predicted transcription factors (TFs) binding sites in promoter regions are based on their over- and underrepresentation in a positive (+) training set in comparison with some negative () training set

Summary

Introduction

Binding of a bacteria to a eukaryotic cell triggers a complex network of interactions in and between both cells. In spite of numerous sophisticated approaches devoted to this subject [1,2,3,4,5,6,7,8,9], we still lack a standard method which would enable us to produce promoter models This may indicate that the existing approaches have their distinct shortcomings and that, the field is still open for new ideas. P. aeruginosa is a pathogen that causes acute and chronic lung infections affecting pulmonary epithelial cells [10,11] We use this example for examining the ways in which the response of the eukaryotic cell(s) is triggered, leading us to a better understanding of the details of the inflammatory process in general

Methods

Results

Discussion

Conclusion