Computation of Maximal Resolution of Copy Number Variation on a Nanofluidic Device using Digital PCR

TL;DR

This paper develops a mathematical framework to determine the maximum resolution of digital PCR devices for detecting copy number variations, and applies it to estimate X chromosome copy number.

Contribution

It introduces a method to compute the maximal distinguishable copy number in digital PCR, enhancing CNV analysis accuracy.

Findings

Computed maximum resolvable copy number for digital PCR

Validated the approach with X chromosome copy number estimation

Provided statistical confidence intervals for CNV detection

Abstract

Copy Number Variations (CNVs) of regions of the human genome are important in disease association studies.The digital array is a nanofluidic biochip which utilizes integrated channels and valves that partition mixtures of sample and reagents into 765 nanovolume reaction chambers. It was recently shown how one can perform statistical analysis of CNV in a DNA sample the digital array. In particular, 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. In this paper we perform 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. Then, 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.