Increased Sample Throughput On Applied Biosystems Genomic Analysis Platform Simplifies Study Of Small RNAs

Multiplexing of up to 256 Samples on SOLiD™ System Improves Workflows, Reduces Cost of RNA Analysis Studies

FOSTER CITY, Calif.--(BUSINESS WIRE)--Research related to the roles that small non-coding RNA molecules play in living cells is one of the fastest growing areas in biology. For these kinds of studies, researchers analyze large numbers of biological samples to examine how patterns of differentially expressed RNAs influence cellular processes related to basic biology and complex diseases such as cancer. To enable scientists to rapidly discover and profile novel small RNA molecules without requiring prior knowledge of sequence information, Applied Biosystems Inc. (NYSE:ABI) today announced the commercial availability of a new small RNA expression analysis solution optimized for the SOLiD™ System, the company's ultra-high-throughput platform for DNA sequencing and genomic analysis research. This solution includes a multiplexing technology (also known as barcoding) that enables the simultaneous analysis of up to 256 biological samples in a single sequencing run. The multiplexing technology is currently available in limited release through an early access program.

This new multiplexing technology is expected to simplify the workflows and reduce the experimental time and cost of applications such as studying the function of small RNA molecules, validation of whole genome association results, targeted resequencing, chromatin immunoprecipitation (ChIP), rare and somatic mutation detection, and epigenetic studies.

Use of this multiplexing technology is expected to dramatically reduce both labor and reagent costs for researchers preparing samples for the SOLiD System by allowing them to pool multiple libraries of nucleic acid fragments which reduces the number of emulsion PCR reactions. These pooled samples can then be sequenced in a single reaction. The combination of the SOLiD System's high sample and sequence throughput allows researchers to use each pooled, labeled set of samples in different slide configurations, enabling the ability to sequence up the 256 samples in a single sequencing run.

The new SOLiD Small RNA Expression Kit provides researchers with an innovative workflow that greatly reduces the time, cost, and experimental variability associated with small RNA library preparation. The SOLiD System is capable of generating up to 240 million sequence reads, or tags per run, for RNA expression analysis applications. The kit converts total RNA into a library suitable for input into the SOLiD System workflow for high-throughput genomic analysis. The simple protocol reduces the library sample preparation workflow to a single day compared to four days with alternative platforms. The kit is expected to improve the detection of biologically relevant changes for researchers working with small RNA molecules. It also requires very small sample quantities, enabling studies not previously possible.

One participant in the early access program for multiplexing technology in expression analysis applications is Jesse M. Gray, Ph.D., postdoctoral research fellow in the laboratory of Dr. Michael E. Greenberg, Ph.D., director of the F. M. Kirby Neurobiology Center at Children's Hospital Boston. For many years, the Greenberg laboratory has been investigating how gene expression changes in response to nerve cell activation. Through whole transcriptome analysis using the small RNA expression kit with multiplexing capability, Dr. Gray has been able to detect and characterize not just whether neuronal activity induces a gene to be expressed, but which variants of that gene are expressed.

"Before we had the multiplexing technology, preparing multiple samples for a transcriptome analysis experiment was time intensive. Currently, use of the SOLiD System multiplexing technology, which allows us to pool 16 samples in one sequencing run, has enabled us to complete the same analysis in one week at a 5 to 10-fold savings in reagents used for the emulsion PCR step," said Dr. Gray. "By using this approach, it is now feasible to include not just one or two, but many different samples or conditions in a sequencing run. This kind of breakthrough on the SOLiD platform will bring us one step closer to making a major shift away from array-based to sequencing-based gene expression assays."

Use of the new small RNA expression analysis solution with multiplexing technology will allow researchers to label individual biological samples with a unique identifier when preparing nucleic acid fragment libraries for tag-based applications, such as RNA expression analysis. By enabling researchers to simultaneously investigate the RNA contents of multiple samples, this technology harnesses the ultra-high-throughput capabilities of the SOLiD System.

One class of small non-coding RNAs that has been studied extensively in recent years is microRNAs, which are gene expression regulatory molecules comprised of about 20 nucleic acid bases. Approximately 6,200 microRNAs have been discovered across organisms; but advances in technology such as the SOLiD System are expected to reveal many more novel molecules of potential scientific interest. Because microRNAs consist of just a few bases, effective profiling of samples for these small RNAs will benefit from a multiplexing technology that allows researchers to investigate greater numbers of samples that require a lower throughput of sequence reads per sample than do large scale genomic analysis studies.

In addition to the multiplexing technology, the SOLiD System's 2-base encoding benefits microRNA profiling studies. In profiling of microRNAs, sequencing allows researchers to discover variants that may occur in different species of these molecules, which can greatly influence the function of the microRNA molecule. For discovery of genetic variants, highly accurate sequencing is necessary for reliable data. The SOLiD System's 2-base encoding chemistry discriminates random or systematic errors from true variants throughout the genome to reveal genetic variants with greater than 99.94 percent accuracy.

"As scientists learn more about the key roles that small RNAs play in biological systems, the SOLiD platform will be integral to enabling new approaches for gene expression analysis," said Shaf Yousaf, president for Applied Biosystems' molecular and cell biology genomic analysis division. "This new small RNA analysis kit, equipped with multiplexing capability, will accelerate these research studies and enable them to be conducted in a more efficient and cost-effective manner."

For more information about the multiplexing technology, please visit: http://marketing.appliedbiosystems.com/mk/submit/SOLID_KNOWLEDGE_RD?_ JS=T&rd=ew

For more information about the SOliD Small RNA Expression Kit, please visit: http://marketing.appliedbiosystems.com/images/Product_Microsites/ Solid_Knowledge_MS/pdf/Small_RNA_AP_f.pdf

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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, ChIP, microbial sequencing, digital karyotyping, medical sequencing, genotyping, gene expression, and small RNA discovery, 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. Applera, 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.

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