Synthetic polynucleotides and methods of use thereof in genetic analysis

The present invention provides a synthetic standard comprising a polynucleotide (e.g., DNA or RNA) comprising a variety of clinically important germline and somatic cell variants. These materials are used to calibrate, assess, and/or validate the performance of polynucleotide-based genetic analytical assays (e.g., NGS assays). In one aspect, the invention provides a method for validating assay performance, comprising generating a synthetic variant DNA fragment comprising a variant having a known allele frequency, where the fragment comprises a molecular tag; combining the synthetic variant DNA with the wild-type DNA to create a test sample; preparing one or more diluents of the test sample; performing a target assay on one or more diluents of the test sample; and comparing the results of the assay using the test sample to the known target allele frequency, thereby verifying the performance of the assay. 本发明提供了一种合成标准品，其包括含有多种临床上重要的种系和体细胞变体的多核苷酸(例如DNA或RNA)。这些材料用于校准、评估和/或验证基于多核苷酸的遗传分析测定法(例如NGS测定法)的性能。在一个方面，本发明提供