Industry Insight: Applied Biosystems – the next generation of sequencing

Posted: 23 November 2007 | | No comments yet

For many years Applied Biosystems has continued to provide robust, reliable tools to analyse DNA and RNA, small molecules, and proteins, in order to make scientific discoveries, develop new pharmaceuticals and conduct standardised testing. Applied Biosystems has developed and introduced dozens of technologies that have catalysed the genomic and proteomics revolutions and are now essential to life science research and applied fields. The company’s biggest contribution has almost certainly been in the development and commercialisation of robust and reliable DNA sequencer technology, and the provision of quality reagents and consumables needed to ensure effective and comparable experimental data. Through the years, our DNA sequencers have remained the gold standard. The first automated DNA sequencer, introduced in 1986, could run 16 samples in a 12-hour cycle, analysing approximately 4,800 base pairs of DNA per day.

By 2002, with the release of the 3730xl DNA Analyzer, we brought high throughput, high quality data and low cost per sample to genetic analysis, with capacity reaching up to two million base pairs of DNA in one 24-hour period. This step up in capabilities was just one example of our continuous stream of development over the following years, which has more recently included products such as the BigDye XTerminator™ Purification Kit that more quickly produces higher quality DNA sequence data and requires less work for purification. Alongside this, new Variant Reporter™ software has been developed for accelerating and streamlining the analysis process for sequence data.

Although current sequencing capacity is far greater and less costly than in the past, the future of sequencing relies heavily on the development of new and innovative products that will make large-scale sequencing projects more efficient and cost effective. The traditional gold-standard Sanger approach to sequencing has been responsible for the complete sequencing of hundreds of microbial and a few higher eukaryote genomes, including human and murine. With the launch of the SOLiD™ System for next generation sequencing, we have met the demand for even faster, cheaper sequencing methods without compromising the quality of the data. The SOLiD System can generate up to four gigabases of mappable data in a single run by the massively parallel reading of millions of DNA fragments, making it the highest throughput system available. Unlike polymerase sequencing approaches, the system uses a proprietary technology called stepwise ligation that can analyse millions of templates simultaneously.

In terms of product development, the new SOLiD System is a good example of our desire to build extensible technologies. This new platform is designed to support higher levels of sequencing throughput per day, using an open slide format amenable to higher bead densities and the existing instrument platform.

In the world of proteomics too, Applied Biosystems, (in partnership with MDS Analytical Technologies), is the number one provider and innovator of quantitative proteomics solutions based on mass spectrometry. In recent years the introduction of iTRAQ® reagents in combination with either the 4800 Plus MALDI TOF/TOF™ Analyzer for maximum depth of protein coverage, or the QSTAR® Elite LC/MS/MS system for speed of analysis, has revolutionised protein identification and expression analysis.

To complement these discovery approaches, the developments of instruments like the QTRAP® LC/MS/MS Systems, are emerging for targeted quantitative proteomic analysis. These hypothesis-driven experiments can monitor tens to hundreds of known proteins or candidate biomarkers simultaneously with very high sensitivity, specificity, and speed, across large numbers of samples to give much greater statistical accuracy.

Applied Biosystems now include the world’s first commercially available miniSTR kit, the AmpFlSTR® MiniFiler™ PCR Amplification Kit. This kit increases the ability to obtain DNA results from compromised samples that previously would have yielded, limited or no genetic data, and gives forensic scientists a better chance of delivering interpretable results from cold cases, as well as new but challenging samples.

Applera, Applied Biosystems, AB (Design), iTRAQ and AmpFlSTR are registered trademarks and SOLiD, MiniFiler, Variant Reporter and BigDye XTerminator are trademarks of Applera Corporation or its subsidiaries in the US and/or certain other countries. QTRAP and QSTAR are registered trademarks and Cliquid, MALDI TOF/TOF and MIDAS are trademarks of Applied Biosystems/MDS Sciex, a joint venture between Applera Corporation and MDS, Inc.

Sue Ann Molero

Sue Ann Molero is currently Senior Marketing Manager for High Throughput Discovery, Applied Biosystems, European Division. She has been at Applied Biosystems for the last 12 years in a variety of marketing roles at the California headquarters, Asia-Pacific and Europe.