October 27, 2007 At the 57th annual meeting of the American Society of Human Genetics, Applied Biosystems announced the worldwide commercial availability of SOLiD, the company’s next-generation DNA sequencing platform. The SOLiD System is an end-to-end next-generation genetic analysis solution comprised of the sequencing unit, chemistry, a computing cluster and data storage which promises unparalleled throughput, scalability, accuracy, and application flexibility.
Virtually all human diseases have genetic underpinnings. Currently, researchers studying complex diseases such as cancer, diabetes, and heart disease rely on reference human DNA sequences from large-scale DNA sequencing projects to broadly associate genetic variations to these diseases. Scientists also use a variety of methods to associate activity or level of expression of specific genes with characteristics of disease. This new era of life-science research calls for technologies that can help scientists to cost-effectively identify how genetic variation and patterns of gene expression contribute to disease, and the manner in which individual genotypes impact how people may respond to various treatments. Although life-science researchers have studied genetic variation and differential gene expression using a wide range of technologies, the use of the SOLiD System is expected to simplify the identification, collection, and analysis of genetic information.
The company began an early-access program for the SOLiD System in June of this year. Since then, the platform has improved throughput 4-fold and increased read lengths by 40%. The current system is capable of delivering up to 4 billion bases of sequence data per run, establishing it as the highest throughput next-generation sequencing platform available today. Data accuracy, another critical performance metric, remains at the highest level of accuracy among next-generation systems. Higher throughput and higher data accuracy result in lower costs for sequencing projects. As part of its early-access program, Applied Biosystems worked closely with customers and collaborators to expand the variety of applications now supported by the system.
“In the new era of next-generation life sciences, higher-throughput sequencing technologies with application flexibility should enable researchers to use a single system to make meaningful associations between variations in the kinds and amounts of DNA sequences and disease,” said Shaf Yousaf, president for Applied Biosystems’ molecular and cell biology systems division. “New approaches to studying genetic variation are expected to profoundly affect pharmaceutical development programs as researchers study how individual genotypes are linked to how people respond to treatments for disease.”
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, enabling the system to exceed 4 gigabases of sequence data per run in Applied Biosystems’ development laboratories. 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 has a raw base accuracy greater than 99.94% after 2-base encoding, a mechanism that discriminates random or systematic errors from true single nucleotide polymorphisms (SNPs). This represents a 5-fold higher accuracy than any data currently published to date on alternative next-generation sequencing platforms. The platform’s high accuracy, combined with mate-pair analysis, enables detection of sequence variation including SNPs, gene copy number variations, single-base duplications, inversions, insertions, and deletions. Mate-pair sample preparation is a method that enables highly accurate sequence assembly, which is necessary for the analysis of complex genomes such as human, mouse and other model organisms.
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.
Leading research institutions around the world are already using the SOLiD System to conduct a wide range of applications. Researchers at the Hubrecht Institute in The Netherlands are studying gene function in animal models, such as /C. elegans/ (roundworm), zebrafish, and rats, so that they can understand the function of similar genes in humans. The researchers are using the SOLiD System to sequence DNA samples from thousands of different animals with up to 10,000 times coverage of genomic regions of interest. This allows them to identify the specific mutations that have been introduced into these genomes. Researchers then associate these varied sequences with observed changes to the organisms. This process helps them to understand gene function in these animal models.
At Columbia University the SOLiD system is being used to compare whole-genome methylation patterns in breast cancer to investigate what roles abnormal patterns of methylation might play in carcinogenesis – the formation of cancer. “The throughput of the SOLiD System is tremendous, quickly reaching the point where we can plan for routine whole-genome methylation profiling of many samples,” said Columbia’s Dr. Edwards. “The scalability of the SOLiD System allows us to confidently make plans to expand our studies and develop new applications and analysis methods for epigenetic profiling that will help us to better understand what role methylation patterns play in carcinogenesis.”
At the University of Queensland in Australia, researchers are studying the transcriptome to better understand important cellular processes such as cell differentiation, kidney damage and repair, and tumor initiation and progression. They are using the SOLiD System for transcriptome analysis to measure the amounts of relevant variant mRNA transcripts expressed in animal models. The SOLiD System is making it possible for them to detect both rarely expressed mRNA transcripts and rare variants of known transcripts.
Meanwhile researchers at the University of Tokyo are studying promotor regions of the genome – the switches that turn genes on and off – to better understand how patterns of gene expression contribute to disease, regulatory networks, and cell differentiation. These scientists are using the SOLiD System to profile transcription start sites (TSS), because to effectively analyze promoter regions it is necessary to determine the location of TSS.
The SOLiD System is already enabling new ways of performing genetic analysis applications, which may set new standards for how scientists are able to approach complex challenges associated with understanding the biological basis for health and disease.
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