Methods and systems for sequence calling
Inventors
Pratt, Mark • Almogy, Gilad • BARTOV, AVISHAI
Assignees
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Publication Number
US-12119087-B2
Publication Date
2024-10-15
Expiration Date
Abstract
The present disclosure provides methods and systems for accurate and efficient context-aware base calling of sequences. In an aspect, disclosed herein is a method for sequencing a nucleic acid molecule, comprising: (a) sequencing the nucleic acid molecule to generate a plurality of sequence signals; and (b) determining base calls of the nucleic acid molecule based at least in part on (i) the plurality of sequence signals and (ii) quantified context dependency for at least a portion of the plurality of sequence signals.
Core Innovation
The invention relates to context-aware processing of a plurality of sequence signals generated upon sequencing a nucleic acid. A system stores the plurality of sequence signals and aligns them to a reference genome in a reference signal database, where the reference genome comprises reference signals. The aligned signals are used to identify a reference locus comprising a homopolymer sequence and to generate a consensus sequence that includes a homopolymer sequence of N bases.
The consensus sequence comprises a homopolymer sequence of N bases based at least on the identified reference locus, a length of the homopolymer sequence of the reference locus, and the reference signal. The disclosed processing also supports generating and using consensus sequences from the plurality of sequence signals aligned to the reference signal.
A further aspect quantifies context dependency of the plurality of sequence signals based at least on a known sequence associated with the plurality of sequence signals. In this context-dependent quantification, the system aligns the plurality of sequence read signals to the reference genome in the reference signal database and quantifies context dependency in the aligned signals using the known sequence. The quantified context dependency is used to support homopolymer length determination and to define context-aware signal-to-homopolymer behavior described by context-specific mappings.
Claims Coverage
The partial content identifies two independent claims (clm-00001 and clm-00011). Together, they cover reference-signal alignment, reference-locus identification for homopolymers, consensus generation with an N-base homopolymer, and quantifying context dependency of aligned sequence signals using a known sequence.
Aligning plurality of sequence signals to a reference signal database
Align the plurality of sequence signals to a reference genome in a reference signal database, wherein the reference genome comprises reference signals.
Identifying a reference locus for a homopolymer sequence
Identify a reference locus comprising a homopolymer sequence based at least on said aligned sequence signals.
Generating a consensus sequence with an N-base homopolymer
Generate a consensus sequence from said plurality of sequence signals aligned to said reference signal, which consensus sequence comprises a homopolymer sequence of N bases, based at least on said identified reference locus, a length of said homopolymer sequence of said reference locus, and said reference signal.
Quantifying context dependency using a known sequence
Quantify said context dependency in said plurality of sequence read signals aligned to said reference signal, based at least on a known sequence associated with said plurality of sequence signals.
Across the independent claims, the core coverage is the combination of reference-signal alignment, reference-locus identification for homopolymers, and consensus generation that includes a homopolymer sequence of N bases; additionally, the claims include quantifying context dependency of aligned signals using a known sequence.
Stated Advantages
Documented Applications
No documented applications found
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