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A new systematic computational approach to predicting target genes of transcription factors.

ABSTRACT: Identifying transcription factor target genes (TFTGs) is a vital step towards understanding regulatory mechanisms of gene expression. Methods for the de novo identification of TFTGs are generally based on screening for novel DNA binding sites. However, experimental screening of new binding sites is a technically challenging, laborious and time-consuming task, while computational methods still lack accuracy. We propose a novel systematic computational approach for predicting TFTGs directly on a genome scale. Utilizing gene co-expression data, we modeled the prediction problem as a 'yes' or 'no' classification task by converting biological sequences into novel reverse-complementary position-sensitive n-gram profiles and implemented the classifiers with support vector machines. Our approach does not necessarily predict new DNA binding sites, which other studies have shown to be difficult and inaccurate. We applied the proposed approach to predict auxin-response factor target genes from published Arabidopsis thaliana co-expression data and obtained satisfactory results. Using ten-fold cross validations, the area under curve value of the receiver operating characteristic reaches around 0.73.

SUBMITTER: Dai X

PROVIDER: S-EPMC1935008 | biostudies-other | 2007

REPOSITORIES: biostudies-other

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A new systematic computational approach to predicting target genes of transcription factors.

Dai Xinbin X He Ji J Zhao Xuechun X

Nucleic acids research 20070618 13

Identifying transcription factor target genes (TFTGs) is a vital step towards understanding regulatory mechanisms of gene expression. Methods for the de novo identification of TFTGs are generally based on screening for novel DNA binding sites. However, experimental screening of new binding sites is a technically challenging, laborious and time-consuming task, while computational methods still lack accuracy. We propose a novel systematic computational approach for predicting TFTGs directly on a g ...[more]

PMID: 17576669

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Project description:BackgroundGenome streamlining, the process by which genomes become smaller and encode fewer genes over time, is a common phenomenon among pathogenic bacteria. This reduction is driven by selection for minimized energy expenditure in a nutrient-rich environment. As pathogens evolve to become more reliant on the host, metabolic genes and resulting capabilities are lost in favor of siphoning metabolites from the host. Characterizing genome streamlining, gene loss, and metabolic pathway degradation can be useful in assessing pathogen dependency on host metabolism and identifying potential targets for host-directed therapeutics.ResultsPoMeLo (Predictor of Metabolic Loss) is a novel evolutionary genomics-guided computational approach for identifying metabolic gaps in the genomes of pathogenic bacteria. PoMeLo leverages a centralized public database of high-quality genomes and annotations and allows the user to compare an unlimited number of genomes across individual genes and pathways. PoMeLo runs locally using user-friendly prompts in a matter of minutes and generates tabular and visual outputs for users to compare predicted metabolic capacity between groups of bacteria and individual species. Each pathway is assigned a Predicted Metabolic Loss (PML) score to assess the magnitude of genome streamlining. Optionally, PoMeLo places the results in an evolutionary context by including phylogenetic relationships in visual outputs. It can also initially compute phylogenetically-weighted mean genome sizes to identify genome streamlining events. Here, we describe PoMeLo and demonstrate its use in identifying metabolic gaps in genomes of pathogenic Treponema species.ConclusionsPoMeLo represents an advance over existing methods for identifying metabolic gaps in genomic data, allowing comparison across large numbers of genomes and placing the resulting data in a phylogenetic context. PoMeLo is freely available for academic and non-academic use at https://github.com/czbiohub-sf/pomelo .

Dataset Information

A new systematic computational approach to predicting target genes of transcription factors.

Publications

A new systematic computational approach to predicting target genes of transcription factors.

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