An Algorithm for Identifying Novel Targets of Transcription Factor Families: Application to Hypoxia-inducible Factor 1 Targets

Yue Jiang, Bojan Cukic, Donald A. Adjeroh, Heath D. Skinner, Jie Lin, Qingxi J. Shen, Bing-Hua Jiang
2009 Cancer Informatics  
Effi cient and effective analysis of the growing genomic databases requires the development of adequate computational tools. We introduce a fast method based on the suffi x tree data structure for predicting novel targets of hypoxia-inducible factor 1 (HIF-1) from huge genome databases. The suffi x tree data structure has two powerful applications here: one is to extract unknown patterns from multiple strings/sequences in linear time; the other is to search multiple strings/sequences using
more » ... ple patterns in linear time. Using 15 known HIF-1 target gene sequences as a training set, we extracted 105 common patterns that all occur in the 15 training genes using suffi x trees. Using these 105 common patterns along with known subsequences surrounding HIF-1 binding sites from the literature, the algorithm searches a genome database that contains 2,078,786 DNA sequences. It reported 258 potentially novel HIF-1 targets including 25 known HIF-1 targets. Based on microarray studies from the literature, 17 putative genes were confi rmed to be upregulated by HIF-1 or hypoxia inside these 258 genes. We further studied one of the potential targets, COX-2, in the biological lab; and showed that it was a biologically relevant HIF-1 target. These results demonstrate that our methodology is an effective computational approach for identifying novel HIF-1 targets.
doi:10.4137/cin.s1054 fatcat:oglwknsfd5c33gnxazuew4vfwa