S. Dube, A. Mir, R.C. Jones, R. Ramakrishnan, and G. Sun (USA)
Copy Number Variation, Digital Polymerase Chain Reaction, Chromosome Aneuploidy, Genetic Variation, Statistical Analysis, Statistical Confidence Intervals
Copy Number Variations (CNVs) of regions of the human genome are important in disease association studies. It was recently shown how one can perform statistical analysis of CNV in a DNA sample utilizing a nanofluidic biochip, known as the digital array. This chip utilizes integrated channels and valves that partition mixtures of sample and reagents into 765 nanovolume reaction chambers. However, when the concentration of the input target molecules is large, a chamber could have multiple molecules. In this recent work, it was shown how one can accurately estimate the true concentration of the molecules in the DNA sample and then determine the ratios of different sequences along with statistical confidence intervals on these estimations. The goals of this paper are two fold. First, we utilize this mathematical analysis by presenting optimal number of positive chambers needed to obtain tightest confidence interval. This leads to computation of maximum number of copies which can be distinguished using the digital array which gives its resolution in terms of its ability to determine CNV. Second, we demonstrate the usefulness of the mathematical analysis to solve an important real-world problem of determination of the copy number of X chromosome as our example application.
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