Drug Discovery Today: Technologies
Vol. 2, No. 3 2005
Editors-in-Chief Kelvin Lam – Pfizer, Inc., USA Henk Timmerman – Vrije Universiteit, The Netherlands DRUG DISCOVERY
TODAY
TECHNOLOGIES
Emerging technologies
Next generation sequencing technologies Thomas Jarvie 454 Life Sciences, 20 Commercial Street, Branford, CT 06405, USA
From the investigation of disease-associated loci in humans, to monitoring the changing genomes of pathogenic viruses and bacteria, sequencing is a powerful and versatile tool. A new generation of sequencing
Section Editors: Steve Gullans – RxGen, Inc., New Haven, CT, USA Robert Zivin – Johnson and Johnson, New Brunswick, NJ, USA
technologies will increase the speed and lower the cost of sequencing, and promises to expand the utility of sequencing in drug discovery and development. Introduction DNA sequencing is a central technology in our understanding of biology and plays a significant, supporting role in drug discovery and development. The Human Genome Project and the resequencing of selected regions of the human genome in disease association studies have contributed to a refined understanding of the molecular basis of many diseases. Sequencing of pathogenic microbes and drug resistant strains has aided in our understanding of drug resistance, the development of drug resistance over time and the mechanism of action of new drugs. Additionally, the sequencing of full viral genomes, or a subset of the genomes, derived from clinical samples provides a picture of the course of infection over time, response to antiviral therapies and an insight into possible strategies for further drug development. This review focuses on the next generation of sequencing technologies and the potential for these technologies to revolutionize pharmaceutical development.
The need for new sequencing methods Electrophoresis-based, Sanger sequencing technology is the most commonly used technology for sequencing and was the E-mail address: T. Jarvie ([email protected]) 1740-6749/$ ß 2005 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.ddtec.2005.08.003
mainstay of the Human Genome Project. A look into the Gold Database (http://www.genomesonline.org/) shows that Sanger-based sequencing has build a solid foundation of genomic sequence that the next generation of technologies can build upon through resequencing and comparative genomics studies. In addition to the whole genome sequencing, Sangerbased sequencing has been used to sequence countless amplicons for applications such as verification of clones, searching for SNPs, forensic analysis and resequencing. Over the past 10 years, significant improvements in Sanger technology have cut the cost of sequencing from $10/kb to $1/kb. Over the same period of time, the throughput for a state of the art instrument has increased from
Vol. 2, No. 3 2005
Editors-in-Chief Kelvin Lam – Pfizer, Inc., USA Henk Timmerman – Vrije Universiteit, The Netherlands DRUG DISCOVERY
TODAY
TECHNOLOGIES
Emerging technologies
Next generation sequencing technologies Thomas Jarvie 454 Life Sciences, 20 Commercial Street, Branford, CT 06405, USA
From the investigation of disease-associated loci in humans, to monitoring the changing genomes of pathogenic viruses and bacteria, sequencing is a powerful and versatile tool. A new generation of sequencing
Section Editors: Steve Gullans – RxGen, Inc., New Haven, CT, USA Robert Zivin – Johnson and Johnson, New Brunswick, NJ, USA
technologies will increase the speed and lower the cost of sequencing, and promises to expand the utility of sequencing in drug discovery and development. Introduction DNA sequencing is a central technology in our understanding of biology and plays a significant, supporting role in drug discovery and development. The Human Genome Project and the resequencing of selected regions of the human genome in disease association studies have contributed to a refined understanding of the molecular basis of many diseases. Sequencing of pathogenic microbes and drug resistant strains has aided in our understanding of drug resistance, the development of drug resistance over time and the mechanism of action of new drugs. Additionally, the sequencing of full viral genomes, or a subset of the genomes, derived from clinical samples provides a picture of the course of infection over time, response to antiviral therapies and an insight into possible strategies for further drug development. This review focuses on the next generation of sequencing technologies and the potential for these technologies to revolutionize pharmaceutical development.
The need for new sequencing methods Electrophoresis-based, Sanger sequencing technology is the most commonly used technology for sequencing and was the E-mail address: T. Jarvie ([email protected]) 1740-6749/$ ß 2005 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.ddtec.2005.08.003
mainstay of the Human Genome Project. A look into the Gold Database (http://www.genomesonline.org/) shows that Sanger-based sequencing has build a solid foundation of genomic sequence that the next generation of technologies can build upon through resequencing and comparative genomics studies. In addition to the whole genome sequencing, Sangerbased sequencing has been used to sequence countless amplicons for applications such as verification of clones, searching for SNPs, forensic analysis and resequencing. Over the past 10 years, significant improvements in Sanger technology have cut the cost of sequencing from $10/kb to $1/kb. Over the same period of time, the throughput for a state of the art instrument has increased from
