Multiplex parallel pair-end-ditag sequencing approaches in system biology

Characterization of all the functional components constituted in human genome relies in our ability to completely elucidate the genetic/epigenetic regulatory networks, chromatin states, nuclear architectures, and genome variations. Such endeavors demand for the development of robust and effective genomic technologies. In the past few years, the availability of disruptive next generation DNA sequencing technologies has offered new promise for whole genome interrogation. However, despite the massive parallel and ultra-high throughput capacity, the common nature of short read lengths found within these platforms limits their applications for many types of whole genome-based analyses. To overcome such constrain, pair end ditag (PET) based sequencing concept was conceived as an immediate solution to expand the information content and extend the linear coverage. By sequencing paired end signatures from any desired DNA fragment and mapping them to the reference genome, PET strategy allows the accurate demarcation of target DNA boundaries and defines their locations on the genomic landscape. Furthermore, the ability to delineate relationship between two ends of a DNA molecule enables the full scale discovery of unconventional gene products, genome rearrangements, and chromatin interactions. Coupling with the massively parallel and ultra-high throughput sequencing platforms, such unique features of PET strategy have the potential to revolutionize the approaches used to decipher regulatory networks in system biology, define the genome organizations, and characterize genome variations; which ultimately leads to the development of strategies for personalized medicine. (C) 2009 John Wiley & Sons, Inc. WIREs Syst Biol Med 2010 2 224-234