© 2008 Oxford University Press
This article appears in the following Nucleic Acid Symposium Series issue: Joint Symposium of the 18th International Roundtable on Nucleosides, Nucleotides and Nucleic Acids and the 35th International Symposium on Nucleic Acids Chemistry [View the issue table of contents]
Quantitative, Sensitive Analysis of DNA and RNA
SEQUENOM, Inc. San Diego, CA USA
*Corresponding Authors; E-mail: ccantor{at}sequenom.com
Abstract
DNA or RNA sequences that contain useful information about disease risk, disease occurrence, therapeutic response, and probable prognosis are potentially valuable biomarkers. They can be accessed by biopsy, or in ideal cases non-invasively from easily accessible fluids like blood or urine. Tolls are available for biomarker discovery, validation, and clinical use. Discovery usually requires whole genome analysis, and currently this is done with either nucleic acid arrays (DNA chips) or sequencing. Validation requires high quality data scalability to large numbers of samples. Clinical utility normally needs a high degree of automation, and for non-invasive approaches, great experimental sensitivity and specificity but on small numbers of samples.
No one platform can efficiently span the broad range of requirements and project sizes. SEQUENOM uses an automated mass spectrometry platform for the quantitative analysis of DNA and RNA in a variety of settings including genotyping, genecopy number measurements, gene expression, epigenetics, and automated bacterial and viral identification.
In collaboration with Amit Meller at Boston University, SEQUENOM is developing optically detected nanospores as a companion platform for its mass spectrometry offering. Both platform use similar homogeneous solution biochemistry to prepare samples. Both platforms depend on vary rapid digital signal processing for real time data analysis and interpretation. The nanopore method uses pores large enough to pass single-stranded DNA but too small to pass double strands. Hence pore passage strips off one of the DNA stands, and optical method are used to detect changes in fluorophores on this strand or attached to reporter probes, as it is stripped. We expect that, when mature, the nanopore method will be extremely const effective for whole genome analysis of genotypes, gene expression, epigenetics, and whole genome sequencing. A key aspect of the nanopore method is its speed. Post sample preparation, many analyses may require only seconds of instrument time.