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2013 ; 7 Suppl 6
(Suppl 6
): S13
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Inferring functional transcription factor-gene binding pairs by integrating
transcription factor binding data with transcription factor knockout data
#MMPMID24565265
Yang TH
; Wu WS
BMC Syst Biol
2013[]; 7 Suppl 6
(Suppl 6
): S13
PMID24565265
show ga
BACKGROUND: Chromatin immunoprecipitation (ChIP) experiments are now the most
comprehensive experimental approaches for mapping the binding of transcription
factors (TFs) to their target genes. However, ChIP data alone is insufficient for
identifying functional binding target genes of TFs for two reasons. First, there
is an inherent high false positive/negative rate in ChIP-chip or ChIP-seq
experiments. Second, binding signals in the ChIP data do not necessarily imply
functionality. METHODS: It is known that ChIP-chip data and TF knockout (TFKO)
data reveal complementary information on gene regulation. While ChIP-chip data
can provide TF-gene binding pairs, TFKO data can provide TF-gene regulation
pairs. Therefore, we propose a novel network approach for identifying functional
TF-gene binding pairs by integrating the ChIP-chip data with the TFKO data. In
our method, a TF-gene binding pair from the ChIP-chip data is regarded to be
functional if it also has high confident curated TFKO TF-gene regulatory relation
or deduced hypostatic TF-gene regulatory relation. RESULTS AND CONCLUSIONS: We
first validated our method on a gathered ground truth set. Then we applied our
method to the ChIP-chip data to identify functional TF-gene binding pairs. The
biological significance of our identified functional TF-gene binding pairs was
shown by assessing their functional enrichment, the prevalence of protein-protein
interaction, and expression coherence. Our results outperformed the results of
three existing methods across all measures. And our identified functional targets
of TFs also showed statistical significance over the randomly assigned TF-gene
pairs. We also showed that our method is dataset independent and can apply to
ChIP-seq data and the E. coli genome. Finally, we provided an example showing the
biological applicability of our notion.