Bioinformatics systems, apparatuses, and methods executed on an integrated circuit processing platform
Inventors
Van Rooyen, Pieter • Ruehle, Michael • McMillen, Robert J.
Assignees
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Publication Number
US-10083276-B2
Publication Date
2018-09-25
Expiration Date
Abstract
A system, method and apparatus for executing a sequence analysis pipeline on genetic sequence data includes a structured ASIC formed of a set of hardwired digital logic circuits that are interconnected by physical electrical interconnects. One of the physical electrical interconnects forms an input to the structured ASIC connected with an electronic data source for receiving reads of genomic data. The hardwired digital logic circuits are arranged as a set of processing engines, each processing engine being formed of a subset of the hardwired digital logic circuits to perform one or more steps in the sequence analysis pipeline on the reads of genomic data. Each subset of the hardwired digital logic circuits is formed in a wired configuration to perform the one or more steps in the sequence analysis pipeline.
Core Innovation
The invention relates to executing one or more steps of a sequence analysis pipeline on genetic data using an integrated circuit that comprises reconfigurable hardwired digital logic circuits interconnected by physical electrical interconnects. The logic circuits are in a wired configuration to access an index of one or more genetic reference sequences and map a plurality of reads of genomic data to one or more segments of the genetic reference sequences according to the index.
The invention further specifies a sequence-analysis flow based on seeds and hash-table structures. The logic circuits extract a seed representing a subset of a sequence of nucleotides represented by the read, calculate an address within the index based on the seed, access the address in the index, and receive a record representing position information in the genetic reference sequence.
For alignment and probabilistic evaluation, the logic circuits receive location information specifying a reference segment, access the genetic reference sequences based on the location information, and align the read of genomic data to the one or more segments to produce aligned genetic sequence data. The invention also includes a wavefront-based dynamic programming aligner with steering and backtrace to generate alignments, and an alternative mode that performs Hidden Markov Model (HMM) operations on a selection of nucleotide sequences from the read and a candidate haplotype sequence to determine a probability.
Claims Coverage
The independent claims cover wired configurations of reconfigurable hardwired digital logic circuits on an integrated circuit for index-based mapping, location-based alignment, and HMM-based candidate haplotype probability determination. Three inventive features are consolidated here.
Wired reconfigurable hardwired logic for index-based read mapping
An integrated circuit with reconfigurable hardwired digital logic circuits interconnected by physical electrical interconnects, including an input for receiving reads, where the logic circuits are in a wired configuration to access an index of one or more genetic reference sequences and map the plurality of reads of genomic data to one or more segments according to the index.
Index-based mapping using seed-derived lookup addresses
The logic circuits extract a seed from the read, calculate an address within the index based on the seed, access the address in the index to receive a record representing position information in the genetic reference sequence, determine one or more matching positions, and output at least one matching position.
Wired location-based alignment and HMM-based candidate haplotype probability
An integrated circuit comprising reconfigurable hardwired digital logic circuits in a wired configuration to receive location information specifying a reference segment, access one or more genetic reference sequences based on the location information, and align the read of genomic data to one or more segments, and a second set of reconfigurable hardwired digital logic circuits to receive a candidate haplotype sequence and the read, compare nucleotide sequences, perform Hidden Markov Model operations, and determine a probability for the candidate haplotype sequence.
The claims center on wired, reconfigurable hardwired digital logic circuits that access an index or reference sequences to map reads and align reads to reference segments, with an additional HMM-based mode for candidate haplotype probability determination.
Stated Advantages
Faster mapping/aligning/sorting compared to BWA.
Improved performance/efficiency in hardware-accelerated secondary/tertiary processing framework.
Rich error model seeded hashing.
Documented Applications
RNA-Seq.
small RNA/miRNA.
ChIP-Seq.
RIP-Seq.
methylation analysis.
SNP calling/discovery.
structural variation/mate-pair.
de novo assembly.
metagenomics.
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