Canonical, Stable, General Mapping using Context Schemes

TL;DR

This paper introduces context schemes, a general and stable method for sequence mapping in genomics that unambiguously recognizes reference bases and supports complex rearrangements, scalable to large query sequences and adaptable to graph-based references.

Contribution

The paper presents context schemes, a novel approach for sequence mapping that ensures unambiguous, stable, and scalable mappings, supporting complex genomic variations and graph-based references.

Findings

High-performance context schemes exist for genomic mapping.

Efficient algorithms for context scheme mapping are developed.

Context schemes support detection of complex rearrangements.

Abstract

Motivation: Sequence mapping is the cornerstone of modern genomics. However, most existing sequence mapping algorithms are insufficiently general. Results: We introduce context schemes: a method that allows the unambiguous recognition of a reference base in a query sequence by testing the query for substrings from an algorithmically defined set. Context schemes only map when there is a unique best mapping, and define this criterion uniformly for all reference bases. Mappings under context schemes can also be made stable, so that extension of the query string (e.g. by increasing read length) will not alter the mapping of previously mapped positions. Context schemes are general in several senses. They natively support the detection of arbitrary complex, novel rearrangements relative to the reference. They can scale over orders of magnitude in query sequence length. Finally, they are trivially extensible to more complex reference structures, such as graphs, that incorporate additional variation. We demonstrate empirically the existence of high performance context schemes, and present efficient context scheme mapping algorithms. Availability and Implementation: The software test framework created for this work is available from https://registry.hub.docker.com/u/adamnovak/sequence-graphs/. Contact: benedict@soe.ucsc.edu Supplementary Information: Six supplementary figures and one supplementary section are available with the online version of this article.