Novel Applications of the Paired-End diTag (PET) Technology in Pharmacogenomics

Kuo   Ping   Chiu

doi:10.2174/187569208784017539

Abstract

Genomics is becoming the integral part of Pharmacogenomics, and the Paired-End diTag (PET) technology is creating a new paradigm in Genomics. The PET technology directly links the 5 terminal tags of cDNAs or genomic sequences with their corresponding 3 terminal tags to form PET ditags and concatenates them for efficient sequencing. The GIS (Gene Identification Signature)-PET analysis was developed for studying transcriptomes and pathway aberrations. It can precisely demarcate the alternative transcription start site (TSS) and the alternative polyadenylation site (PAS). The paired-end nature makes the identification of fusion genes, fusion transcripts, and pseudogenes very straightforward. Additionally, PET-associated genes can be correlated to pathway database to systematically reveal global pathway aberrations. Changes in metabolic and signal transduction pathways can be compared across different cell types. Later, the ChIP (Chromatin immunoprecipitation)-PET analysis was developed. This approach facilitates genome-wide mapping of transcription factor binding sites (TFBSs), as shown in the studies of p53, c-Myc, estrogen receptor, Oct4/Nanog/Sox2, STAT1, NFκB. In addition, study of trimethylations of lysine4 and lysine27 in H3 histone protein demonstrated the capability of ChIP-PET for genome-wide mapping of epigenetic modifications. Integration of all these PET data would produce a comprehensive picture of genetic and epigenetic cis-acting elements, gene expression and regulation, and pathway activities; and data can be analyzed and compared at molecular, gene, and pathway levels. This article reviews the advancement of the PET technology and discusses its potential applications in Pharmacogenomics.

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