Abstract: Disclosed is a method for improving the sensitivity and accuracy of quantitative detection of polynucleotides in a sample, such a clinical specimen, by a method that utilizes a two- or three-step process of tagging/labeling target molecules and adding an adapter sequence for adding a universal primer for efficient amplification of targets while decreasing target amplification bias. When combined with the step of statistically correcting for sequencing errors, the method can significantly increase the accuracy of quantitative detection of polynucleotides in a sample.