Applied Biosystems Expands Sequencing-Based RNA Analysis Solutions Portfolio

SOLiD™ Whole Transcriptome Expression Kit Provides Comprehensive, Specific Analysis of All Known RNAs Present in Biological Samples

FOSTER CITY, Calif.--(BUSINESS WIRE)--Applied Biosystems Inc. (NYSE:ABI) today announced the development of a sequencing-based molecular tool for the genomic analysis of whole transcriptomes, the vast collection of RNAs transcribed from a genome. This technology, which provides detailed characterization of expressed protein-encoding genes, identifies many non-coding RNAs, and includes sample multiplexing capability, is expected to be available for limited release through an early access program that will begin in November 2008. This offering will expand the company's RNA expression analysis solutions portfolio for use with its SOLiD™ System, the company's ultra-high-throughput genomic analysis platform.

The SOLiD™ Whole Transcriptome Expression Kit is expected to provide researchers greater insights into biological pathways and molecular mechanisms that regulate cell fate decision, development and disease progression. The kit is designed to provide new views of a cell's transcriptome, such as expression of non-coding RNAs, identification of alternative splicing events, expressed SNPs (single nucleotide polymorphisms) or mutations, or translocations and fusion transcripts. The application of the kit should advance treatment of complex diseases, such as diabetes, heart disease and cancer, and accelerate time course studies in which analysis of differential RNA expression provides insight into the level and mechanism of action of a particular treatment.

John McPherson, Ph.D., cancer genomics director at the Ontario Institute for Cancer Research (OICR), is cataloging genetic alterations that occur in different types of cancers to better classify tumors and identify the important early events driving the disease. He has been exploring different approaches for identifying how genetic variants in both coding and non-coding RNA transcripts impact cancer formation. OICR will be one of the customer sites evaluating the whole transcriptome kit.

"We recognize the growing importance of understanding how altered expression of genetic variants contributes to the formation of complex diseases such as cancer," said Dr. McPherson. "Of the various technologies available for detecting expression levels of disease-specific genetic variants where altered expression provides insights into the disease, sequencing-based methods for RNA expression analysis provide the most specific measurement possible, especially for detecting all kinds of alterations that can occur to both coding and non-coding RNA transcripts. I'm very interested in evaluating this new technology from Applied Biosystems for RNA expression analysis applications."

Like the recently introduced SOLiD Small RNA Expression Kit, the whole transcriptome kit is based on proprietary Ambion® technology and is expected to provide researchers with an innovative workflow that greatly reduces the time, cost, and experimental variability associated with RNA library preparation. Use of either of these kits is expected to reduce the time researchers need to prepare samples for RNA analysis by approximately 50 percent, compared to alternative approaches. Applying multiplexing further simplifies the downstream workflow for RNA analysis. For example, using the multiplexing capability of the kit, up to 10 RNA libraries can be sequenced simultaneously, thereby reducing the cost of analysis per sample. In addition, the technology conserves strandedness of cDNA which allows researchers to discern between overlapping RNAs transcribed from the sense or antisense strand.

The SOLiD System is capable of generating up to 240 million sequence reads, or tags per run, for RNA expression analysis applications. This is the highest demonstrated throughput for a sequencing-based RNA expression analysis application. This throughput is necessary to assure the highest sensitivity and dynamic range for these kinds of applications. Also, the high number of tags enables researchers to multiplex samples in a single sequencing reaction, further reducing the cost of this type of analysis.

Currently, the most widely used method to analyze global patterns of gene expression is the DNA microarray. However, because microarrays are hybridization-based technologies, they are unable to detect RNA transcripts expressed at low levels and they cannot be used to detect RNA transcripts from repeated sequences. Additionally, microarrays offer limited dynamic range to detect subtle changes in expression level of target genes, which is critical in understanding biological response to stimuli or environmental changes. By enabling global, hypothesis-neutral analysis of gene expression profiles, researchers who use this kit will be able to detect all known and novel RNAs present in biological samples, with no bias toward known RNA molecules as with probe-based array technologies.

"Global transcriptome analysis is becoming a crucial area of investigation for researchers who strive to have a more complete understanding of the human genome," said Shaf Yousaf, president for Applied Biosystems' molecular and cell biology genomic analysis division. "The whole transcriptome kit will follow on the recent launch of the SOLiD Small RNA Expression kit, providing the company a broad portfolio of tools for analysis of coding and non-coding RNAs on a genomic analysis platform. Based on the positive reception we received for the small RNA kit, we accelerated our efforts to develop a kit for whole transcriptome analysis based on the same Ambion technology."

To use the SOLiD Whole Transcriptome Expression Kit, researchers first isolate and purify total RNA or mRNA from cell or tissue samples. Since the whole transcriptome kit is not limited to human samples, it can also be used to analyze the transcriptomes of model organisms in agricultural study applications. Ribosomal RNA is removed from these samples, followed by a RNA fragmentation step. Researchers then hybridize and ligate adapters to these RNA fractions, and a reverse transcription reaction results in double stranded cDNA. Since both adapters are ligated in a defined manner, the strandedness of cDNA is conserved in the resulting library. Data analysis tools will also be available to early access participants, and accessible to all researchers on the SOLiD System Software Community website.

By developing genome, epigenome and transcriptome analysis solutions for its genomic analysis platforms, Applied Biosystems continues to advance science, demonstrating its leadership by helping scientists to better understand the biology underlying health and disease.

For more information about the SOLiD RNA expression analysis portfolio, please visit solid.appliedbiosystems.com.

About the SOLiD System
The SOLiD System is an end-to-end genomic analysis solution comprised of a sequencing unit, 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 and targeted resequencing, transcriptome analysis, small RNA discovery, gene expression profiling, chromatin immunoprecipitation (ChIP), microbial and eukaryotic resequencing, digital karyotyping, medical sequencing, and genotyping, among others.

Unparalleled throughput, scalability and accuracy distinguish the SOLiD System from other next generation 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 of nearly 15 billion bases of mappable sequence data per run in customer laboratories, and has demonstrated runs of greater than 20 billion bases of mappable sequence data at Applied Biosystems' research and development facilities. 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 system's current hardware or software. The SOLiD System's unique 2-base encoding provides built-in error checking capability that distinguishes random or systematic errors from true single base changes, or single nucleotide polymorphisms (SNPs). This capability helps researchers to detect SNPs with greater than 99.94 percent sequencing accuracy.

About Applied Biosystems Inc.
Applied Biosystems Inc. (formerly known as Applera Corporation) is a global leader in the development and marketing of instrument-based systems, consumables, software, and services for academic research, the life science industry and commercial markets. Driven by its employees' belief in the power of science to improve the human condition, the company commercializes innovative technology solutions for DNA, RNA, protein and small molecule analysis. Customers across the disciplines of academic and clinical research, pharmaceutical research and manufacturing, forensic DNA analysis, and agricultural biotechnology use the company's tools and services to accelerate scientific discovery, improve processes related to drug discovery and development, detect potentially pathogenic microorganisms, and identify individuals based on DNA sources. Applied Biosystems has a comprehensive service and field applications support team for a global installed base of high-performance genetic and protein analysis solutions. Applied Biosystems Inc. is headquartered in Norwalk, CT. On June 12, 2008, Applera Corporation and Invitrogen Corporation (NASDAQ:IVGN) announced that their Boards of Directors had approved a definitive merger agreement under which Invitrogen will acquire all of the outstanding shares of Applied Biosystems stock. The merger is subject to customary closing conditions and is targeted to close in the fall of 2008. Further information regarding the merger will be provided in a joint proxy statement/prospectus to be mailed to stockholders of the company and Invitrogen. Investors and security holders are urged to read this document when it becomes available because it will contain important information. Information about Applied Biosystems, including reports and other information filed by the company with the Securities and Exchange Commission, is available at http://www.appliedbiosystems.com. All information in this news release is as of the date of the release, and Applied Biosystems 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 our 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, we note 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 our filings with the Securities and Exchange Commission.

For Research Use Only. Not for use in diagnostic procedures.

©Copyright 2008. Applied Biosystems Inc. All rights reserved. Applied Biosystems, and AB (Design) are registered trademarks and SOLiD is a trademark of Applied Biosystems Inc. or its subsidiaries in the U.S. and/or certain other countries. Ambion is a registered trademark of Ambion, Inc., an Applied Biosystems Business.

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