Aspects of coverage in medical DNA sequencing

Background: DNA sequencing is now emerging as an important component in biomedical studies of diseases like cancer. Short-read, highly parallel sequencing instruments are expected to be used heavily for such projects, but many design specifications have yet to be conclusively established. Perhaps the most fundamental of these is the redundancy required to detect sequence variations, which bears directly upon genomic coverage and the consequent resolving power for discerning somatic mutations. Results: We address the medical sequencing coverage problem via an extension of the standard mathematical theory of haploid coverage. The expected diploid multi-fold coverage, as well as its generalization for aneuploidy are derived and these expressions can be readily evaluated for any project. The resulting theory is used as a scaling law to calibrate performance to that of standard BAC sequencing at 8

• Type: Journal
• Year: 2008
• Where: BMCBI
• Authors: Michael C. Wendl, Richard K. Wilson
• Keywords: BMCBI 2008, Sequencing, Sequencing Coverage Problem, Somatic Mutations