REVIEWOpen AccessGenomic sequencing in clinical trialsKaren K Mestan1*, Leonard Ilkhanoff2, Samdeep Mouli3and Simon Lin4AbstractHuman genome sequencing is the process by which the exact order of nucleic acid base pairs in the 24 humanchromosomes is determined. Since the completion of the Human Genome Project in 2003, genomic sequencing israpidly becoming a major part of our translational research efforts to understand and improve human health anddisease. This article reviews the current and future directions of clinical research with respect to genomicsequencing, a technology that is just beginning to find its way into clinical trials both nationally and worldwide.We highlight the currently available types of genomic sequencing platforms, outline the advantages anddisadvantages of each, and compare first- and next-generation techniques with respect to capabilities, quality, andcost. We describe the current geographical distributions and types of disease conditions in which thesetechnologies are used, and how next-generation sequencing is strategically being incorporated into new andexisting studies. Lastly, recent major breakthroughs and the ongoing challenges of using genomic sequencing inclinical research are discussed.Keywords: Clinical trial, DNA, sequencing, human genome, bioinformaticsIntroductionHuman genome sequencing, the process by which theexact order of nucleic acid base pairs in the 24 humanchromosomes is determined, was the most significanttechnical challenge of the Human Genome Project.Completed in 2003, the 13-year project identified 20,000to 25,000 genes and determined the sequence of the 3billion chemical base pairs that make up human DNAas well as the regions that control them. Since then,improvements in sequencing speed, reliability, and costhave been the ongoing goals. Hence, genomic sequen-cing is rapidly becoming a major part of our transla-tional research efforts to understand and improvehuman health and disease. With the numerous advancesin genomic sequencing, there has been a dramaticincrease in the number of clinical trials now using thistechnology to study key disease outcomes [1].The objective of this review is to familiarize the trans-lational investigator with genomic sequencing technolo-gies as they apply to clinical trials. We describe thecurrently available types of genomic sequencing plat-forms, outline the advantages and disadvantages of each,and compare first- and next-generation techniques withrespect to capabilities, quality, and cost. To illustrate therecent impact and widespread movement of genomicsequencing into clinical and translational research, weprovide a summary of the types and distribution of clini-cal studies that are using genomic sequencing toenhance the understanding of complex pathophysiologyand identify important biomarkers of both rare andcommon diseases. We provide some key examples ofclinical trials in which translational researchers are uti-lizing this technology to better identify and individualizethe management of high-risk patients, and to achievemajor breakthroughs in drug development.Features of First- and Next-GenerationSequencingSo rapid are the advances in genomic sequencing tech-nology that the methods are commonly referred to asfirst- and next-generation sequencing (NGS). Sangersequencing, developed in the 1990s, was the earliestmethod used to sequence human DNA. In fact, it wasSanger technology that was used to sequence thehuman genome in the Human Genome Project. It isoften referred to as “first-generation sequencing”because it revolutionized how a single lab couldsequence millions (rather than thousands) of base pairs.Sanger sequencing is a multi-channel capillary approachthat allows relatively rapid DNA sequencing. Even* Correspondence: k-mestan@northwestern.edu1Department of Pediatrics, Division of Neonatology, Northwestern UniversityFeinberg School of Medicine, Chicago, IL, USAFull list of author information is available at the end of the articleMestan et al. Journal of Translational Medicine 2011, 9:222http://www.translational-medicine.com/content/9/1/222© 2011 Mestan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.
