Applied Biosystems Genomic Analysis Platform Fuels New Era of Life-Sciences Research

When Applied Biosystems (NYSE:ABI), an Applera Corporation business, introduced its ultra-high-throughput genomic analysis system less than a year ago, the company entered a new era of life-science research, enabling scientists to adopt new approaches for studying the genetic basis of health and disease. Researchers at the Broad Institute of MIT and Harvard, as well as Columbia University Medical Center (CUMC), have adopted innovative approaches for their research related to large-scale discovery of genetic variation and cancer research, respectively. This week, scientists from these institutions will present preliminary findings from their research using the SOLiD™ System at the Cold Spring Harbor Laboratory’s Biology of Genomes meeting in New York. As part of its ongoing commitment to commercializing best-in-class genomic analysis platforms, Applied Biosystems today announced significant new enhancements to the SOLiD System platform, the company’s new technology for DNA sequencing and genomic analysis research. These include upgrades to software and chemistry that double throughput, simplify workflows and decrease system run times. These enhancements are expected to support future innovative approaches to some of the most important areas of research for the scientific community. "The SOLiD System has already had a tremendous impact in driving significant life-science research, including important projects related to medically relevant genetic variation and cancer research,” said Shaf Yousaf, president for Applied Biosystems’ molecular and cell biology genomic analysis division. "These new performance enhancements enable the SOLiD System to continue to establish new standards for ultra-high-throughput genomic analysis, helping Applied Biosystems to maintain its established leadership in DNA sequencing and other high-throughput genomic analysis applications.” Large-Scale Discovery of Genetic Variation at the Broad Institute Researchers at the Broad Institute are using the SOLiD System for large-scale discovery of genetic variation in human genome samples. This research is expected to be included as part of the Broad Institute’s contribution to the 1000 Genomes Project, a worldwide research effort sponsored by the National Human Genome Research Institute (NHGRI), the Wellcome Trust and the Beijing Genomics Institute. This project will involve the sequencing of 1,000 genomes from people from around the world to create the most detailed and medically useful picture to date of human genetic variation. The data generated as part of the 1000 Genomes Project are expected to reveal clues about how variant DNA sequences contribute to conditions such as cancer, diabetes and heart disease. In analysis of DNA single base changes – also known as SNPs (single nucleotide polymorphisms) – scientists at the Broad Institute used two SOLiD Systems to generate more than 50 billion bases of DNA sequence over the past six weeks. At the Cold Spring Harbor Laboratory meeting, Dr. Chad Nusbaum, co-director of the Broad Institute’s genome biology program, will present highly accurate polymorphism discovery data from a human genome sample that belongs to a trio, which is a family of a father, mother, and offspring. Among other findings, Dr. Nusbaum’s team will report that SNPs discovered as a result of using the SOLiD System were matched with high accuracy to a database of known SNPs. Genomic analysis platforms capable of ultra-high throughput are quickly becoming established as the standard for the study of complex genomes because as the technologies mature, the cost of analysis continues to decrease. The Broad Institute completed sequencing experiments with yields of up to 13.4 billion bases per run; more than two times the number of bases that comprise an entire diploid human genome. Methylation Profiling Studies at Columbia University Medical Center Reveal Clues about Breast Cancer The SOLiD System is helping researchers at Columbia University Medical Center (CUMC) to develop new approaches to methylation profiling studies of cancer. In these kinds of studies, researchers evaluate patterns of methylation, which is a chemical modification to DNA, at CpG sites in the genome. Dense regions of these sites are often located near gene promoters and within repetitive regions of the genome, where cytosine (C) and guanine (G) nucleotides are present in tandem at greater frequency than in other parts of the genome. Researchers study patterns of methylation in these CpG-rich regions as to better understand how methylation contributes to cancer. These scientists, including Dr. John Edwards, associate research scientist at CUMC’s genome center, and Dr. Timothy Bestor, a professor in CUMC’s department of genetics and development, have been using the SOLiD System to help carry out a novel approach for studying whole-genome methylation profiles of a panel of breast cancer tumors and normal controls. This approach incorporates the mate-pair analysis capabilities of the SOLiD System to map the methylation state of all regions of the genome, including promoters, genic regions, and repetitive elements. Mate-pair analysis – the ability of a genetic analysis system to analyze pairs of sequences separated by a known distance between them – allows researchers to precisely determine where those sequences are located in the genome. At the Cold Spring Harbor Laboratory meeting this week, Dr. Edwards will present data of whole-genome methylation profiles of a panel of tumors and matched normal controls that show, for the first time, in a whole genome context, the differences in methylation patterns between normal and tumor breast tissue. Based on this data, Dr. Edwards will describe a new role for methylation in cancer, where methylation changes in particular regions of cancer genomes may reflect a cellular defense system that kills cancerous cells. "Using the SOLiD System, we have interrogated the methylation status of more than 500 million CpG sites, which far exceeds the sum total of methylation data previously available,” said Dr. Bestor. "The DNA data quality of runs from the platform that included the new performance enhancements has been excellent.” SOLiD System Enhancements Set New Levels of Performance and Ease-of-Use for Genomic Analysis Applied Biosystems this week is making available new upgrades to chemistry and software that will double throughput, simplify workflows and decrease system run times. These enhancements will be a part of all future shipments of the SOLiD System. These enhancements will also be made available to existing customers through local service and support teams located around the world. With these new enhancements, the SOLiD System can consistently generate more than 6 billion bases of sequence data per run, which doubles throughput levels compared to when the system became commercially available just six months ago. This level of throughput maintains the SOLiD System as the highest throughput genomic analysis system available today. The SOLiD System is expected to scale further, as it has already demonstrated more than 10 billion bases per run at some customer locations, and up to 17 billion bases at Applied Biosystems’ research and development facilities. In addition to the number of bases sequenced per run, throughput can also be measured by the number of sequence tags that a genetic analysis system can generate for quantitative applications, such as gene expression profiling, identification of transcription factor binding sites, and serial analysis of gene expression (SAGE). Sequence tags, derived from short pieces of mRNA transcripts, are used for sequencing-based quantitative gene expression techniques. These techniques, such as SAGE, are used to rapidly identify differences in genome-wide patterns of gene expression, which could be associated with disease, regulatory cell networks or cell differentiation. With the upgrades to software and chemistry announced today, the SOLiD System now generates up to 240 million sequence tags per run. This increase in throughput of sequence tags is expected to further reduce the cost of conducting sequencing-based gene expression applications. Upgrades to chemistry and software have also resulted in improvements to sample preparation methods. These improvements are expected to result in simplified workflows, with less DNA sample now being required for use in DNA sequencing and RNA analysis applications. The number of manual pipetting steps researchers need to perform when preparing samples used in emulsion PCR have also been reduced. A smaller emulsion device, an optimized emulsion PCR protocol, and software upgrades have significantly shortened run times for both fragment and mate-pair library runs. Another result is higher quality data for most sequencing reactions, including more even representation of bases across the entire sequence composition range – GC content – of the genome. Many of the new performance enhancements are possible because of the inherent scalability and flexibility of the SOLiD System platform. Unparalleled throughput and scalability distinguish the SOLiD System infrastructure from other genomic analysis sequencing platforms. The system can be scaled to support a higher density of sequence reads per slide through bead enrichment. Beads are an integral part of the SOLiD System’s open-slide format architecture. 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. The SOLiD System also has the flexibility to accommodate future approaches to life science research. For example, the unique flexibility of the system’s 2-slide format enables researchers to simultaneously perform two independent applications, such as genotyping and gene expression. About the SOLiD System The SOLiD System is an end-to-end 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. 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. Further information about the SOLiD System is available at http://solid.appliedbiosystems.com. 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. 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 unless required by law. Applied Biosystems Forward Looking Statements Certain statements in this press release are forward-looking. These may be identified by the use of forward-looking words or phrases such as "should, "planned," and "expect," among others. These forward-looking statements are based on Applera Corporation's current expectations. The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for such forward-looking statements. In order to comply with the terms of the safe harbor, Applera Corporation notes that a variety of factors could cause actual results and experience to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. 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. For Research Use Only. Not for use in diagnostic procedures. ©Copyright 2008. Applied Biosystems. All rights reserved. Applera, Applied Biosystems, and AB (Design) are registered trademarks and SOLiD is a trademark of Applera Corporation or its subsidiaries in the U.S. and/or certain other countries.