Wellcome Trust Sanger Institute and Applied Biosystems Announce Project to Advance Study of Cancer Genomics
Researchers to Use SOLiD(TM) System for Comprehensive Coverage of Genetic Changes That Occur in Development of Disease CAMBRIDGE, England & FOSTER CITY, Calif.–Researchers from the United Kingdom and the United States are working together to investigate one of science’s most challenging mysteries – the genetic underpinnings of cancer in the human genome. The Wellcome Trust Sanger Institute, a leading genome research institute, and Applied Biosystems (NYSE:ABI – News), an Applera Corporation business, are sequencing a cancer genome and normal DNA from the same individual to comprehensively detect and characterize the genetic changes that occur during the development of the disease. The purpose of this research is to provide the highest resolution picture to date of genetic variation in the development of cancer. Preliminary scientific findings resulting from this collaboration will be presented at the Cold Spring Harbor Laboratory’s Biology of Genomes meeting in New York from May 6 – 10. In this collaboration, scientists will use five Applied Biosystems SOLiD™ Systems in an effort to sequence the genomes of a small cell lung cancer cell line, and a non-cancerous cell line and comprehensively cover all of the genomic variations in both cell lines. This project is expected to advance research recently carried out by The Sanger Institute’s Cancer Genome Project that examined low coverage of structural variation in cancerous and normal cell lines. Structural variants consist of gene copy-number variations, single-base duplications, inversions, translocations, insertions and deletions. In this project, by surveying both single-base changes – SNPs (single nucleotide polymorphisms) – and larger segments of genomic rearrangements, or structural variations, researchers expect to obtain more in-depth coverage of all types of genetic variation that contribute to cancer. The scientific research to be conducted by Applied Biosystems and The Sanger Institute will advance cancer research already accomplished as part of The Sanger Institute’s Cancer Genome Project. In that study, researchers found that the number of driver mutations – those that drive the development of cancer – is greater than previously thought, suggesting that many more genes contribute to cancer development. Researchers believe that the use of highly accurate, ultra-high throughput genomic analysis technologies will now help them to more thoroughly investigate how these mutations, including SNPs and structural variants, contribute to the development of cancer. The development of sophisticated genomic analysis sequencing technologies has opened the door to a new era of life-science research, in which there is potential to find genetic variations, including rare mutations that contribute to complex diseases. The use of these sequencing technologies for cancer research can enable the complete survey of cancer genomes within individuals. Scientists at The Sanger Institute have been using SOLiD Systems to employ a DNA sequencing technique known as deep-shotgun resequencing to obtain DNA sequence information of both cancerous and normal genomes from the same individual. Deep shotgun resequencing refers to the sequencing of an entire genome using very large numbers of small DNA fragments, such that every base is likely to be covered many times. In this collaboration, scientists from both organizations plan to increase sequence coverage of both genomes by identifying one SNP for every 500,000 bases of DNA. They anticipate that such low frequency SNP detection will be made possible by the SOLiD System’s high accuracy, which includes 2-base encoding. The platform’s 2-base encoding chemistry discriminates random or systematic errors from true SNPs to reveal SNPs with greater than 99.94 percent sequencing accuracy. One of the goals of this research is to generate 20-fold genome coverage of the cancer genome and 20-fold genome coverage of normal DNA using paired-end reads of a wide range of insert sizes, making use of the SOLiD System’s ability to analyze insert sizes of up to 10,000 base pairs from both cancer and normal DNA. Insert sizes are pairs of sequences separated by a known distance between them. The scientists will use mate-pair analysis on the SOLiD System, a crucial technique which enables highly accurate sequence assembly and the detection of a comprehensive range of sequence variation. Scientists at The Sanger Institute have been using multiple mate-pair insert sizes ranging from 400 base pairs to 3,500 base pairs to help create a catalog of mutations in an individual cancer. This portrait of genetic variation will offer researchers the ability to lay the groundwork for a complete cataloging of the events that are required for the generation of individual cancers. “The Wellcome Trust Sanger Institute Cancer Genome Project is dedicated to implementing sophisticated genomic analysis technologies in the study of somatic changes in cancer genomes,” said Professor Mike Stratton, co-leader of The Sanger Institute’s Cancer Genome Project. “We anticipate that the SOLiD System’s high-throughput capabilities will allow us to cost-effectively reduce the number of runs needed to achieve the 20-fold coverage we are seeking, and will enable us to identify and recognize single nucleotide polymorphisms and rearrangements more accurately.” The SOLiD System is an end-to-end next-generation genomic analysis solution comprised of the sequencing unit, chemistry, a computing cluster and data storage. The platform is based on sequencing by oligonucleotide ligation and detection. Unlike polymerase sequencing approaches, the SOLiD System utilizes a proprietary technology called stepwise ligation, which generates high-quality data for applications including: whole genome sequencing, chromatin immunoprecipitation (ChIP), microbial sequencing, digital karyotyping, medical sequencing, genotyping, gene expression, and small RNA discovery, among others. Unparalleled throughput and scalability distinguish the SOLiD System from other genetic analysis sequencing platforms. The system can be scaled to support a higher density of sequence per slide through bead enrichment. Beads are an integral part of the SOLiD System’s open-slide format architecture, which enables the system to generate greater than 6 gigabases of sequence data per run. The SOLiD System has demonstrated runs greater than 10 gigabases per run at customer locations. The combination of the open-slide format, bead enrichment, and software algorithms provide the infrastructure for allowing it to scale to even higher throughput, without significant changes to the platform’s current hardware or software. “Applied Biosystems’ collaboration with The Sanger Institute allows us to extend our leadership in genomics research by applying our technology to advance important studies that impact the human condition,” said Shaf Yousaf, president for Applied Biosystems’ molecular and cell biology genomic analysis division. “We believe that the SOLiD System is well suited to carry out studies of complex genomes and will play a significant role in new discoveries in cancer research.” Applied Biosystems is a global leader in the development and commercialization of instrument-based systems, consumables, software, and services for the life-science market. The company is the market leader for DNA sequencing platforms. In addition to the SOLiD System for next-generation DNA sequencing, the company offers a full line of capillary electrophoresis-based systems and chemistries. Today, more than 14,000 of Applied Biosystems’ genetic analyzers are actively in use and have contributed to the sequencing of more than 450 completed genomes and approximately 700 others in progress. Capillary electrophoresis provides a proven method for sequence and fragment analysis for a variety of applications. The SOLiD System expands the boundaries of sequencing to enable new applications such as large-scale resequencing, hypothesis-neutral expression, methylation, and ChIP experiments. For some applications, the two platforms will be used at different points in the experimental process. Further information about the SOLiD System is available at http://solid.appliedbiosystems.com. About Wellcome Trust Sanger Institute The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992 as the focus for UK sequencing efforts. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms such as mouse and zebrafish, and more than 90 pathogen genomes. In October 2005, new funding was awarded by the Wellcome Trust to enable the Institute to build on its world-class scientific achievements and exploit the wealth of genome data now available to answer important questions about health and disease. These programmes are built around a Faculty of more than 30 senior researchers. The Wellcome Trust Sanger Institute is based in Hinxton, Cambridge, UK. Information about the Wellcome Trust Sanger Institute is available at http://www.sanger.ac.uk. About Applera Corporation and Applied Biosystems Applera Corporation consists of two operating groups. Applied Biosystems serves the life science industry and research community by developing and marketing instrument-based systems, consumables, software, and services. Customers use these tools to analyze nucleic acids (DNA and RNA), small molecules, and proteins to make scientific discoveries and develop new pharmaceuticals. Applied Biosystems’ products also serve the needs of some markets outside of life science research, which we refer to as “applied markets,” such as the fields of: human identity testing (forensic and paternity testing); biosecurity, which refers to products needed in response to the threat of biological terrorism and other malicious, accidental, and natural biological dangers; and quality and safety testing, such as testing required for food and pharmaceutical manufacturing. Applied Biosystems is headquartered in Foster City, CA, and reported sales of approximately $2.1 billion during fiscal 2007. The Celera Group is a diagnostics business delivering personalized disease management through a combination of products and services incorporating proprietary discoveries. Berkeley HeartLab, a subsidiary of Celera, offers services to predict cardiovascular disease risk and optimize patient management. Celera also commercializes a wide range of molecular diagnostic products through its strategic alliance with Abbott and has licensed other relevant diagnostic technologies developed to provide personalized disease management in cancer and liver diseases. Information about Applera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available at http://www.applera.com, or by telephoning 800.762.6923. Information about Applied Biosystems is available at http://www.appliedbiosystems.com. 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These factors include but are not limited to: (1) rapidly changing technology and dependence on customer acceptance of the SOLiD System; (2) the risk of unanticipated difficulties associated with the further development of the SOLiD™ System; and (3) other factors that might be described from time to time in Applera Corporation’s filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Applera does not undertake any duty to update this information, including any forward-looking statements, unless required by law.