Applied Biosystems Debuts New SOLiD(TM) 3 System Expected to Enable $10K Genome

Applied Biosystems (NYSE:ABI) today announced a new genomic analysis platform, the SOLiD™ 3 System, that is expected to enable scientists to sequence a human genome for approximately $10,000. Significant cost-reduction and productivity enhancements have been built into the company’s latest ultra-high-throughput genomic analysis platform, enabling researchers to dramatically drive down the cost of sequencing entire genomes of all organisms, and expand applications for RNA and epigenetic analysis. Use of this system is expected to help life science researchers move one step closer to the mainstream use of genomic data for clinical research and personalized medicine.

Earlier this year, Applied Biosystems used the SOLiD 3 System’s underlying oligonucleotide ligation and detection technology to sequence a human genome for less than $60,000. Technical enhancements to the new platform that enable higher sample and data throughput are expected to further decrease the cost of genomic sequencing. For example, the availability of lower cost genomic data is expected to accelerate disease association and biomarker discovery studies to improve diagnostics and disease management, support clinical trials that successfully match the right treatments for individuals, and help the general population to better understand their individual genetic makeup.

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, has been using the SOLiD Small RNA Expression Kit with multiplexing capability to investigate gene expression changes in response to nerve cell activation. He believes that the inherent scalability and sensitivity of the SOLiD technology has advantages for many sequencing-based and tag counting applications.

"The $10,000 genome represents yet another striking decrease in the cost per base for sequencing projects,” said Dr. Gray. "The reduced cost of sequencing will allow us to include more experimental time-points in our studies and run more experiments overall. This significant cost decrease will also allow for higher throughput across all types of sequencing experiments, not just for sequencing human genomes.”

Reducing Cost of Sequencing-based Applications

There are a number of attributes associated with the SOLiD 3 System that should enable researchers to greatly reduce the cost of sequencing projects, and increase their productivity for all applications, such as upgrades to the system architecture, streamlined workflows, and multiplexing capabilities. Taken together, these cost reduction and productivity attributes are expected to significantly reduce the time and resources needed to generate sufficient coverage of genomes of humans and other organisms.

System Architecture Supports Industry’s Highest Throughput Sequencing Platform

The open-slide format architecture of the SOLiD 3 System uses beads containing DNA sample to input genomic information into the system. These beads are added to slides that are analyzed by the system. The new platform supports the deposit of high densities of beads per slide, which results in the generation of up to 20 gigabases of mappable sequence data per run. The combination of the open-slide format, bead enrichment, and software algorithms provides the infrastructure for allowing the platform to scale to even higher levels of throughput, without significant changes to the underlying technology. The inherent scalability of the platform, or the ability to sequence higher densities of DNA sample per run, enables approximately 7-fold coverage across the entire human genome in a single run. Enhancements to the system architecture combined with a new powerful compute cluster, easier slide loading, optimized chemistry, and longer read lengths of more than 50 base pairs, result in a platform that enables cost-effective sequencing and targeted resequencing applications.

Streamlined Workflows Shorten Time to Results

Enhancements that streamline workflows for sequencing applications shorten the time needed to obtain data from samples, saving labor and reducing reagent costs. The SOLiD 3 System includes walk-away automation, which facilitates up to seven days of unattended operation. This reduces the need for technician interaction with the platform and increases laboratory productivity. The system’s multiplexing capability, which will be useful for applications of resequencing, small RNA expression and whole transcriptome analysis, is expected to dramatically reduce both labor and reagent costs for researchers preparing samples for the SOLiD 3 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 3 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 to 256 samples in a single sequencing run. Additionally, pre-filled and pre-mixed reagent tubes reduce the number of steps needed when preparing samples. Altogether, these technology improvements enable researchers to more rapidly convert samples into mappable sequence data and reduce run times by up to 42%, compared to earlier versions of the platform.

Comprehensive Software Suite Simplifies Data Analysis

The optimization of system software and the development of data analysis software tools are expected to streamline the analysis of multiple genomic regions across large numbers of samples and simplify the discovery of biological variation. These software improvements, including email notification, automated offline analysis, remote monitoring and new application-specific analysis tools are expected to help researchers better manage data related to genomic analysis studies.

A Platform for a Systems-Biology Approach to Studying Organisms

With unsurpassed sensitivity, the SOLiD 3 System allows researchers to adopt a systems-biology approach to studying simple and complex organisms. Systems biology is the study of an organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions. On a single platform, researchers can use a global, hypothesis-neutral approach to survey the contents of genomes, transcriptomes, and epigenomes, or the collection of chemical modifications to DNA. By using the SOLiD 3 System for this systems-biology approach, researchers will be able to detect most known and novel messenger RNAs (mRNAs) present in single cells, with no bias toward known mRNA molecules as with current probe-based array technologies. The new platform is capable of detecting more than 400 million sequence tags per run, allowing researchers to survey approximately four mouse or human transcriptomes in a single run, while maintaining the sensitivity to detect molecules present at a single copy per cell.

"In this sense, SOLiD 3 and the $10,000 genome will help scientists using this platform to harness the natural sensitivity advantage that sequencing-based RNA expression analysis has over microarray studies,” added Dr. Gray. "The longer read lengths in the SOLiD 3 System are particularly exciting for being able to detect novel splice forms in RNA expression analysis experiments.”

Kenneth S. Kosik, M.D., Harriman Professor of neuroscience research, and co-director of the Neuroscience Research Institute at the University of California at Santa Barbara, is studying how microRNA expression regulates cell differentiation. Dr. Kosik believes that the SOLiD 3 System will allow him to adopt a hypothesis-neutral approach to investigating how non-coding RNAs regulate brain function, brain tumor formation, and possibly neurodegeneration.

"In our research, it’s very important to be able to quickly and reliably detect known and novel RNAs including non-coding RNAs so that we can learn more about how they function in the mechanisms of neural plasticity and their impairment in neurodegeneration,” said Dr. Kosik. "A technology, like the SOLiD 3 System, that provides the sensitivity to detect novel or rare transcripts in a hypothesis-neutral manner, offers the scalability for high sample throughput. This approach will greatly enhance our ability to understand the role of non-coding RNAs in regulating gene expression and ultimately in brain function.”

Expanded Support for a Variety of Genomic Analysis Applications

Researchers have utilized the SOLiD technology for a variety of applications, including transcriptome analysis, chromatin immunoprecipitation, microbial sequencing. Enhancements to the new SOLiD 3 System, including longer read lengths and the incorporation of an imaging buffer that improves signal to noise ratios, will enable researchers to utilize the platform for de novo sequencing of microbial genomes, resequencing for candidate gene studies, methylation profiling of silenced genes, and digital karyotyping of biological samples. The superior accuracy of the system, greater than 99.94% with 2-base encoding, provides researchers performing studies of genetic variation with the highest data quality compared to other sequencing platforms. Use of the system for genetic variation studies enables researchers to detect novel single base changes, or SNPs, with less coverage than is needed when using competitive sequencing platforms and fewer false positive results.

Applied Biosystems has continued to develop DNA sequencing platforms since the launch of the industry’s first automated DNA sequencer in 1986. This marked the beginning of an ongoing commitment from the company to evolve its DNA sequencing chemistries, systems and analytical tools to meet the increasing demands of the scientific community for higher-throughput, more sophisticated DNA sequencing solutions. Today, more than 14,000 of Applied Biosystems’ genetic analyzers are actively utilized in research and regulated markets, and have contributed to the sequencing of more than 450 completed genomes.

"In less than two decades, Applied Biosystems has evolved three generations of sequencing technology from gel slabs to capillary electrophoresis to next-generation sequencing, and is now providing a platform that is expected to ultimately accelerate the realization of personalized medicine,” said Mark Stevenson, Applied Biosystems’ president and chief operating officer. "With our new SOLiD 3 System, scientists will be able to generate more genetic information in a matter of weeks than was produced by the Human Genome Project in ten years.”

About the SOLiD 3 System

The SOLiD 3 System is the life science industry’s most comprehensive solution from sample to results. The platform is based on sequencing by oligonucleotide ligation and detection. Unlike polymerase sequencing approaches, the platform utilizes a proprietary technology called stepwise ligation, which generates the industry’s most cost-effective and accurate mappable sequence data for a variety of applications. The SOLiD 3 System is capable of generating 20 billion bases of mappable sequence data per run in customer laboratories, and has demonstrated runs of greater than 25 billion bases of mappable sequence data at Applied Biosystems’ research and development facilities. The SOLiD 3 System is supported by one of the life-science industry’s most comprehensive service and support organization of more than 2,000 dedicated field personnel worldwide, specializing in business consulting and protocol development, instrument optimization, and data and application integration. Further information about the SOLiD 3 System is available at http://solid.appliedbiosystems.com.

The SOLiD 3 System is available as an upgrade to an existing platform, or as a stand-alone instrument. To receive the SOLiD 3 upgrade, contact a regional service representative, who can install components that include a new compute cluster, automation components and reagent cooling hardware, and software. The SOLiD 3 System is expected to be globally available in early 2009.

About Applied Biosystems Inc.

Applied Biosystems Inc. (formerly known as Applera Corporation) develops and markets 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 has been provided in a joint proxy statement/prospectus mailed to stockholders of the company and Invitrogen. Investors and security holders are urged to read this document because it contains 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.

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