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US 2016/0102348 A1Published application
Methods, systems, and computer-readable media for accelerated base calling
AssigneeLife Technologies Corporation
InventorBenjamin DONNET
Life of this patent
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Abstract
Embodiments disclose methods, systems, and computer-readable media for accelerated base calling of sequencing data. These methods may be adapted to accelerate sequence determination for data arising from a variety of different nucleic acid sequencing platforms. In various embodiments, configurable logic circuits such as FPGAs and GPUs may be adapted to perform raw signal processing, basecalling, and/or sequence determination operations providing further enhancements to the sequence analysis methods.
Claims20
A method for sample nucleotide sequence determination, the method comprising:
- (a) flowing nucleotides onto a sensor array adapted for sequencing, the sensor array including a first well containing a sample polynucleotide;
- (b) receiving from the sensor array, signal data relating to chemical reactions resulting from the flow of nucleotides, the signal data including a phase-synchrony error component;
- (c) processing the signal data using a hardware-embedded basecaller that identifies putative basecalls corresponding to a nucleotide sequence for the sample polynucleotide using a plurality of parallel channels, each channel processing a selected nucleotide identification hypothesis using a normalization module to identify gain and offset associated with the phase-synchrony error component of the signal data generating normalized signal data, and a solver module that further evaluates the normalized signal data and identifies a putative basecall corresponding to the normalized signal data;
- (d) generating from the putative basecalls, a resulting nucleotide identification with the highest confidence of being attributable to a select nucleotide flow;
- (e) repeating steps (c)-(d) such that for each iteration of the basecaller the nucleotide sequence of the sample polynucleotide is extended by at least one nucleotide;
- and
- (f) outputting the resulting identified nucleotide sequence for the sample polynucleotide.
4 more elements
A system for sample nucleotide sequence determination comprising:
- a sensor array adapted for sequencing, the sensor array including a first well containing a sample polynucleotide and configured to receive a plurality of flows of nucleotides;
- a signal data processor that receives signal data from the sensor array, the signal data resultant from chemical reactions associated with the flow of nucleotides and including a phase-synchrony error component;
- a basecall processor that receives signal data from the signal data processor and identifies putative basecalls corresponding to a nucleotide sequence for the sample polynucleotide using a plurality of parallel channels, wherein each channel further comprises (a) a normalization component that processes a selected nucleotide identification hypothesis identifying gain and offset associated with the phase-synchrony error component of the signal data generating normalized signal data, (b) a solver component that further evaluates the normalized signal data and identifies a putative basecall corresponding to the normalized signal data, and (c) a best candidate selector that generates a resulting nucleotide identification with the highest confidence of being attributable to a select nucleotide flow;
- and
- a data output module that assembles the resulting nucleotide identifications and outputs an identified nucleotide sequence for the sample polynucleotide.
2 more elements
An sequence determination apparatus comprising:
- a basecall processor that receives signal data from a sequencing instrument and identifies putative basecalls corresponding to a nucleotide sequence for a sample polynucleotide contained in a first well of a sensor array associated with the sequencing instrument wherein the signal data results from chemical reactions that take place for a plurality of flows of nucleotides into the first well during sequencing on the sequencing instrument;
- a plurality of parallel channels implemented as a plurality of logic gates within the basecall processor, each channel comprising:
- (a) a normalization component that processes a selected nucleotide identification hypothesis identifying gain and offset associated with the phase-synchrony error component of the signal data generating normalized signal data, (b) a solver component that further evaluates the normalized signal data and identifies a putative basecall corresponding to the normalized signal data, and (c) a best candidate selector that generates a resulting nucleotide identification with the highest confidence of being attributable to a select nucleotide flow;
- and
- a data output module that assembles the resulting nucleotide identifications and outputs an identified nucleotide sequence for the sample polynucleotide.
2 more elements
Dependencies are inferred from the claim text.