Bioinformatics systems, apparatuses, and methods for performing secondary and/or tertiary processing

Abstract

A system, method and apparatus for executing a bioinformatics analysis on genetic sequence data is provided. Particularly, a genomics analysis platform for executing a sequence analysis pipeline is provided. The genomics analysis platform includes one or more of a first integrated circuit, where each first integrated circuit forms a central processing unit (CPU) that is responsive to one or more software algorithms that are configured to instruct the CPU to perform a first set of genomic processing steps of the sequence analysis pipeline. Additionally, a second integrated circuit is also provided, where each second integrated circuit forming a field programmable gate array (FPGA), the FPGA being configured by firmware to arrange a set of hardwired digital logic circuits that are interconnected by a plurality of physical interconnects to perform a second set of genomic processing steps of the sequence analysis pipeline, the set of hardwired digital logic circuits of each FPGA being arranged as a set of processing engines to perform the second set of genomic processing steps. A shared memory is also provided.

What is claimed is: 
     
         1 . A genomics analysis system for executing a sequence analysis pipeline on genetic sequence data, the genetic sequence data including one or more of a read of genomic sequence data from a subject, a genetic reference sequence, an index of the genetic reference sequence, and a candidate haplotype sequence, the genomics analysis platform comprising:
 a cloud accessible server comprising one or more of a first integrated circuit, each first integrated circuit forming a central processing unit (CPU) or graphic processing unit (GPU) having a first set of physical electronic interconnects, the CPU or GPU being responsive to one or more software algorithms that are configured to instruct the CPU or GPU to perform a first set of genomic processing operations of the sequence analysis pipeline, wherein the first set of genomic processing operations include one or more steps in a first set of secondary processing operations;   one or more of a second integrated circuit, each second integrated circuit forming a field programmable gate array (FPGA) having a second set of physical electronic interconnects to connect with at least one CPU or GPU via a portion of the first set of physical electronic interconnects, the FPGA being configurable by firmware to arrange a set of configurable hardwired digital logic circuits to perform a second set of secondary processing operations of the sequence analysis pipeline, the set of hardwired digital logic circuits of each FPGA being arranged as a set of processing engines to perform the second set of secondary processing operations, wherein the second set of secondary processing operations include one or more steps in a mapping and/or an aligning operation as well as a Hidden Markov Model (HMM) operation; and   a memory electronically connectable with one or more of each CPU or GPU and each FPGA via at least a portion of one or more of the first and second set of physical electronic interconnects, the memory being accessible by each CPU or GPU and each FPGA to provide the genetic sequence data thereto, and to store result data from the first and second sets of secondary processing operations performed on the genetic sequence data by each CPU and each FPGA.   
     
     
         2 . The genomics analysis system in accordance with  claim 1 , wherein the second set of secondary processing operations comprises both a mapping and an aligning operation. 
     
     
         3 . The genomics analysis system in accordance with  claim 2 , wherein the second set of secondary processing operations include an aligning operation, wherein the aligning operation comprises one or more of a Smith-Waterman, a Burrows-Wheeler, and a Needleman-Wunsch alignment operation. 
     
     
         4 . The genomics analysis system in accordance with  claim 3 , wherein the aligning operation comprises one or more of a gapped or a gapless alignment. 
     
     
         5 . The genomics analysis system in accordance with  claim 4 , wherein the aligning operation is a Smith-Waterman alignment, and the Smith-Waterman alignment includes a back trace operation. 
     
     
         6 . The genomics analysis system in accordance with  claim 1 , wherein the read of genomic sequence data comprises a plurality of reads of genomic sequence data, and the CPU and/or GPU is configured to merge the plurality of reads into one or more contiguous nucleotide sequences. 
     
     
         7 . The system in accordance with  claim 6 , wherein merging the plurality of reads comprises constructing a De Bruijn graph, from which the candidate haplotype is generated. 
     
     
         8 . The genomics analysis system in accordance with  claim 7 , wherein the HMM operation comprises:
 accessing, from the memory, at least some of a sequence of nucleotides in the read of genomic sequence data and a candidate haplotype sequence, the candidate haplotype sequence comprising a sequence of nucleotides;   comparing the at least some of the sequence of nucleotides in the read of genomic sequence data to the sequence of nucleotides in the candidate haplotype sequence; and   performing the HMM analysis on the at least some of the sequence of nucleotides in the read of genomic sequence data and at least some of the sequence of nucleotides in the candidate haplotype sequence to produce HMM result data, the HMM result data comprising a probability that the candidate haplotype sequence represents the true genetic sequence of a subject.   
     
     
         9 . A system for executing a sequence analysis on a read of genomic data, derived from a genetic sequence of a subject, using a candidate haplotype sequence to determine a probability of observing the read of genomic data assuming the candidate haplotype sequence is a true representation of the subject's genetic sequence, each read of genomic data and the candidate haplotype sequence representing a sequence of nucleotides, the system comprising:
 a cloud accessible server; and   an integrated circuit connected with the cloud-based server, the integrated circuit being formed of a set of configurable hardwired digital logic circuits that are interconnected by a plurality of physical electrical interconnects, one or more of the plurality of physical electrical interconnects comprising a memory interface for the integrated circuit to access a memory, the configurable hardwired digital logic circuits being arranged as a first set of processing engines, the first set of processing engines to perform a plurality of steps in the sequence analysis on the read of genomic data and the candidate haplotype sequence, the first set of processing engines comprising a variant calling module in a first hardwired configuration to:
 receive both a candidate haplotype sequence and a read of genomic data via one or more of the plurality of physical electrical interconnects, both the candidate haplotype sequence and the read of genomic data comprising a sequence of nucleotides; 
 compare the sequence of nucleotides of the candidate haplotype sequence to the sequence of nucleotides of the genomic data; 
 perform one or more Hidden Markov Model (HMM) operations on each of the nucleotide sequences of the read of genomic data and the candidate haplotype sequence; 
 determine a probability for the candidate haplotype sequence to thereby determine whether the candidate haplotype sequence is a true representation of the subject's genetic sequence. 
   
     
     
         10 . The system in accordance with  claim 9 , wherein the integrated circuit is a field programmable gate array (FPGA), and wherein the hardwired digital logic circuit of each processing engine is formed by a programming of the FPGA. 
     
     
         11 . The system in accordance with  claim 10 , wherein the cloud-accessible server comprises one or more of a central processing unit (CPU) and a graphics processing unit (GPU) that is responsive to one or more software algorithms that are configured to instruct the CPU and/or GPU to perform a first set of sequence analysis processing steps on the read of genomic data to generate the candidate haplotype sequence. 
     
     
         12 . The system in accordance with  claim 11 , wherein the read of genomic data comprises a plurality of reads of genomic data, and the CPU and/or GPU is configured to merge the plurality of reads into one or more contiguous nucleotide sequences. 
     
     
         13 . The system in accordance with  claim 12 , wherein the CPU and/or GPU is further configured for generating the one or more candidate haplotypes from the one or more contiguous nucleotide sequences. 
     
     
         14 . The system in accordance with  claim 13 , wherein merging the plurality of reads comprises constructing a De Bruijn graph from which graph the candidate haplotype is generated. 
     
     
         15 . A genomics analysis system for executing a sequence analysis pipeline on genetic sequence data from a subject, the genetic sequence data including a plurality of reads of genomic sequence data from a subject, a genetic reference sequence, an index of the genetic reference sequence, and a candidate haplotype sequence, the genomics analysis platform comprising:
 a cloud accessible server comprising one or more of a first integrated circuit, each first integrated circuit forming a central processing unit (CPU) or graphic processing unit (GPU) having a first set of physical electronic interconnects, the CPU or GPU being responsive to one or more software algorithms that are configured to instruct the CPU or GPU to merge the plurality of reads into one or more contiguous nucleotide sequences, wherein merging the plurality of reads comprises constructing a De Bruijn graph from which the candidate haplotype sequence is generated; and   one or more of a second integrated circuit, each second integrated circuit forming a field programmable gate array (FPGA) having a second set of physical electronic interconnects to connect with at least one of the CPU or GPU via a portion of the first set of physical electronic interconnects, the FPGA being configurable by firmware to arrange a set of configurable hardwired digital logic circuits to perform a set of secondary processing operations, wherein the set of secondary processing operations include performing a Hidden Markov Model (HMM) operation on the candidate haplotype sequence, wherein the HMM operation comprises:   accessing, from a memory, at least some of a sequence of nucleotides in the read of genomic sequence data and the candidate haplotype sequence, the candidate haplotype sequence comprising a sequence of nucleotides;   comparing the at least some of the sequence of nucleotides in the read of genomic sequence data to the sequence of nucleotides in the candidate haplotype sequence; and   performing the HMM analysis on the at least some of the sequence of nucleotides in the read of genomic sequence data and at least some of the sequence of nucleotides in the candidate haplotype sequence to produce HMM result data, the HMM result data comprising a probability that the candidate haplotype sequence represents the true genetic sequence of a subject.   
     
     
         16 . The genomics analysis system in accordance with  claim 15 , wherein the CPU or GPU is further configured for accessing the MINI results data, and further performing a variant call operation on the MINI results data to generate variant call results data. 
     
     
         17 . The genomics analysis system in accordance with  claim 16 , wherein the CPU or GPU is further configured for accessing the variant call results data, and further configured for performing a tertiary analysis on the variant results data. 
     
     
         18 . The genomics analysis system in accordance with  claim 17 , wherein the tertiary analysis is performed for determining whether the subject should be included or excluded from a clinical trial. 
     
     
         19 . The genomics analysis system in accordance with  claim 17 , wherein the tertiary analysis comprises one or more of: determining a marker for a disease, determining a disease variant, determining a potential for a disease, making a clinical interpretation based on a variant analysis, and generating a disease profile or diagnosis for the subject. 
     
     
         20 . The genomics analysis system in accordance with  claim 17 , wherein the generating of the disease profile or diagnosis for the subject comprises one or more of: Non-invasive prenatal testing, a NICU test, a Laboratory Developed Test, and a cancer diagnosis.