Applied Biosystems announces early-access program for its next-generation sequencing platform

Applied Biosystems, an Applera Corporation business, has announced the launch of the early-access program for its next-generation DNA sequencing system. The company said that it has shipped initial units of its SOLiD™ System to leading research institutions that include Stanford University, and has begun accepting orders from other customers.

The SOLiD platform, based on sequencing by oligonucleotide ligation and detection, is Applied Biosystems’ next-generation system for ultra high throughput DNA analysis. Unlike polymerase sequencing approaches, the SOLiD System utilises a proprietary technology called stepwise ligation, which generates high quality data for applications such as whole genome sequencing, medical sequencing, genotyping, gene expression and small RNA discovery.

The promise of next-generation sequencing technology is to broaden the applications of genomic information in medical research and health care, reduce the cost of DNA sequencing without sacrificing quality, and enable discoveries that may revolutionise the practice of medicine.

Applied Biosystems acquired prototype technology for next-generation sequencing from Agencourt Personal Genomics in July 2006 and has rapidly developed the SOLiD System. In less than a year, Applied Biosystems has increased sample throughput five-fold and base read length by 66 per cent, resulting in a system that is expected to accelerate advances in medical research, health care and other life science applications.

Applied Biosystems is developing applications for the SOLiD System in collaboration with leading academic and research institutions that include Stanford, Broad Institute, Wellcome Trust Sanger Institute, Baylor College of Medicine, Joint Genome Institute, University of Queensland (Australia), and Washington University among others. This development process has resulted in one of the most advanced ultra high throughput next-generation sequencing platforms. The SOLiD System is distinguished by the following attributes:

• The SOLiD System features 2-base encoding, a proprietary mechanism that interrogates each base twice for errors during sequencing. The application of 2-base encoding rules during analysis removes measurement errors, resulting in high accuracy sequence data.
• The SOLiD System can generate more than one gigabase of useable data per run, which makes it one of the highest throughput next-generation sequencing systems. A gigabase is a measure that is the equivalent of one third of the human genome, which contains 3 billion bases of DNA.
• The SOLiD System’s high accuracy, combined with mate-pair analysis, enables detection of sequence variation including, SNPs (single nucleotide polymorphisms), gene copy number variations, single base duplications, inversions, insertions and deletions. Mate-pair sample preparation is a method that enables highly accurate sequence assembly required for the analysis of complex genomes such as human, mouse and other model organisms. Combined with high accuracy, mate-pair analysis provides scientists with a flexible system that performs a variety of different applications, including gene expression studies for the detection of low-expressed genes, which are invisible on hybridisation arrays.
• The SOLiD System is designed to accommodate future sequencing applications. Adaptable to bead enrichment, the SOLiD platform can be scaled to support a higher density of sequence per slide. This provides the infrastructure for performing more complex genome studies as they are undertaken.

“We have made rapid progress in developing the SOLiD System, which we believed had the best commercial viability among more than 40 next-generation sequencing technologies we evaluated,” said Mark P. Stevenson, president for Applied Biosystems’ molecular and cell biology division. “We will continue to work with our customers and collaborators to further refine the system and develop the breadth of applications for what we believe will be the life science community’s platform of choice for both current and future DNA analysis projects.”

Scientists at Stanford University have been using results generated on the SOLiD System to better understand complex biological processes. Dr Arend Sidow, PhD, an associate professor at Stanford School of Medicine, has analysed 282 megabases of aligned sequence data generated by the SOLiD System. Dr Sidow was able to create a high resolution map of nucleosome positioning in C. elegans (round worm), a model organism in the study of biological processes. The location of nucleosomes - tightly wound packing units of DNA - is thought to affect gene expression and provide insights into important regulatory mechanisms such as DNA transcription.

“I believe the SOLiD System technology has the potential to deliver real breakthroughs in any application of sequencing aimed at understanding biological functions in complex genomes,” said Dr Sidow. “After evaluating a number of potential technologies, we look forward to applying this ultra high throughput technology to projects such as targeted resequencing of cancer genes and other medically relevant research.”

In a microbial sequencing project, Dr George Weinstock, PhD, co-director at the Human Genome Sequencing Center at Baylor College of Medicine, first sequenced a strain of Escherichia coli using Sanger sequencing technologies. He then used the SOLiD System to resequence the genome for validation of the assembly. The SOLiD System read pair data identified a large duplication that had been missed in the assembly of the Sanger sequences.

“The mate-pair technology in the SOLiD System will enable us to generate highly accurate sequence data for infectious disease pathogens and other microbes,” said Dr Weinstock. “In our future efforts, we will continue to correlate phenotypes with genotypes of bacteria that have closely related genomes. For this research, we look forward to next-generation sequencing technologies capable of identifying all kinds of genetic variation that may occur between different species.”

Dr Elaine Mardis, PhD, director of technology development and co-director at the Genome Sequencing Center at Washington University School of Medicine, is an expert in the development of DNA sequencing technology. She is responsible for the many procedures and high throughput automated systems currently in use at the Genome Sequencing Center.

“We are very enthusiastic about being an early access site for the Applied Biosystems SOLiD System,” said Dr. Mardis. “Early access to the SOLiD System will enable us to evaluate this very important next-generation sequencing platform, and to develop key applications that capitalise on the strengths of this system. Early access to this system will perpetuate our long and productive relationship with Applied Biosystems.”

Applied Biosystems is a global leader in the development and commercialisation of instrument-based systems, consumables, software, and services for the life science market. The company commercialised the technology that helped scientists to sequence the human genome. By developing the SOLiD System, Applied Biosystems continues its leadership in DNA sequencing by commercialising technology that helps scientists to better understand and treat disease, based on genomic information.