METHODS AND SYSTEMS FOR DETECTING SEQUENCE VARIANTS

摘要

The invention provides methods for identifying rare variants near a structural variation in a genetic sequence, for example, in a nucleic acid sample taken from a subject. The invention additionally includes methods for aligning reads (e.g., nucleic acid reads) to a reference sequence construct accounting for the structural variation, methods for building a reference sequence construct accounting for the structural variation or the structural variation and the rare variant, and systems that use the alignment methods to identify rare variants. The method is scalable, and can be used to align millions of reads to a construct thousands of bases long, or longer.

主权项

1. A method for identifying a mutation in proximity to a structural variation in a sequence, the method comprising the steps of:
obtaining a plurality of nucleic acid sequence reads, wherein at least one nucleic acid read comprises a mutation; applying said reads to a reference sequence construct comprising at least two alternative sequences at a position in the construct, one of which is a structural variation; scoring sequence overlaps for each nucleic acid read against the reference construct; aligning each read to a location on the construct such that the score for each read is maximized; and identifying the mutation as being aligned within 100 bp or fewer of the structural variation.