Methods and system for detecting sequence variants

Abstract

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.

Description

[0001] related application [0002] This application claims priority to US Patent Application Nos. 61 / 884,380 and 14 / 041,850, both of which were filed on September 30, 2013 and both of which are incorporated by reference in their entirety. technical field [0003] The present invention relates to methods and systems for aligning sequences (eg, nucleic acid sequences) to each other to generate contiguous sequence reads corresponding to a sample (eg, a genetic sample). The invention additionally relates to methods for identifying variants in a sample. Background technique [0004] Genetics has evolved from an analytical science to an information science. However, scientists have previously struggled to figure out how to extract and identify nucleic acids, and such techniques now seem less important. Next-generation sequencing (eg, whole-transcriptome shotgun sequencing, pyrosequencing, ion semiconductor sequencing, sequencing-by-synthesis) can generate millions of reads cov...

AI Technical Summary

Problems solved by technology

[0040] Because the inability to detect rare variants close to structural variants significantly limits the quality of genetic analysis, there is a need for sequence alignment techniques that can account for structural variants, resulting in better alignment of rare mutations or variants

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