DETERMINATION OF NUCLEIC ACID SEQUENCE IMBALANCE

Abstract

Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists in a biological sample. One or more cutoff values ​​are selected to determine an imbalance, for example, the ratio of two sequences (or sets of sequences). The cutoff value can be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, that contains a background of maternal nucleic acid sequences. 1 [ cutoff value can be determined based on an average concentration of a sequence per reaction. In one aspect, the cutoff value is determined by a proportion of informative wells that are estimated to contain a particular nucleic acid sequence, wherein the proportion is determined based on the aforementioned percentage and / or average concentration. The cutoff value can be determined using many different types of methods, such as sequential likelihood ratio testing (SPRT).