# US 9,519,752 B2 · Bioinformatics systems, apparatuses, and methods executed on an integrated circuit processing platform

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- Number: US 9,519,752 B2
- Document ID: US9519752B2
- Status: Granted
- Kind: B2
- Application number: 14/988,666
- Filed: 2016-01-05
- Published: 2016-05-12
- Granted: 2016-12-13
- Earliest claimed: 2013-01-17
- Assignees: Edico Genome, Corp.
- Applicants: Edico Genome, Inc.
- Inventors: Pieter Van Rooyen; Robert J. Mcmillen; Michael Ruehle
- Web page: https://patentgrep.com/patent/US9519752B2

## CPC

- G16B 50/30: Data warehousing; Computing architectures
- G06F 13/16: for access to memory bus (G06F13/28 takes precedence)
- G06F 13/4068: {Electrical coupling}
- G06F 13/4265: {on a point to point bus (G06F13/4247, G06F13/4282 take precedence)}
- G16B 30/00: ICT specially adapted for sequence analysis involving nucleotides or amino acids
- G16B 30/10: Sequence alignment; Homology search
- G16B 30/20: Sequence assembly
- G16B 40/00: ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
- G16B 40/10: Signal processing, e.g. from mass spectrometry [MS] or from PCR
- G16B 50/00: ICT programming tools or database systems specially adapted for bioinformatics
- G16B 50/50: Compression of genetic data
- H03K 19/17736: Structural details of routing resources
- H10D 84/90: Masterslice integrated circuits
- H10D 84/907: {CMOS gate arrays}
- H10D 89/10: Integrated device layouts
- H10W 20/01: {Manufacture or treatment}
- H10W 20/064: {by modifying the conductivity of conductive parts, e.g. by alloying}
- H10W 20/43: Layouts of interconnections
- H10D 84/938: {Implementation of memory functions}
- H10D 84/983: {Levels of metallisation}
- Y02D 10/00: Energy efficient computing, e.g. low power processors, power management or thermal management
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G06F: ELECTRIC DIGITAL DATA PROCESSING (computer systems based on specific computational models G06N)
- H03K: PULSE TECHNIQUE (measuring pulse characteristics G01R; modulating sinusoidal oscillations with pulses H03C; transmission of digital information H04L; discriminator circuits detecting phase difference between two signals by counting or integrating cycles of oscillation H03D3/04; automatic control, starting, synchronisation or stabilisation of generators of electronic oscillations or pulses where the type of generator is irrelevant or unspecified H03L; coding, decoding or code conversion, in general H03M)
- H10D: INORGANIC ELECTRIC SEMICONDUCTOR DEVICES
- H10W: GENERIC PACKAGES, INTERCONNECTIONS, CONNECTORS OR OTHER CONSTRUCTIONAL DETAILS OF DEVICES COVERED BY CLASS H10
- Y02D: CLIMATE CHANGE MITIGATION TECHNOLOGIES IN INFORMATION AND COMMUNICATION TECHNOLOGIES [ICT], I.E. INFORMATION AND COMMUNICATION TECHNOLOGIES AIMING AT THE REDUCTION OF THEIR OWN ENERGY USE

## Abstract

A system, method and apparatus for executing a sequence analysis pipeline on genetic sequence data includes an integrated circuit 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 integrated circuit 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.

## Claims

### Claim 1

A system for executing a sequence analysis pipeline on genetic sequence data, the system comprising:
a memory for storing one or more genetic reference sequences, an index of the one or more genetic reference sequences, and a plurality of reads of genomic data, each of the genetic reference sequences and the plurality of reads of genomic data comprising a sequence of nucleotides; and
an integrated circuit formed of a set of 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 the memory, the hardwired digital logic circuits being arranged as a set of processing engines, each processing engine being formed of a subset of the hardwired digital logic circuits to perform at least one step in the sequence analysis pipeline on the plurality of reads of genomic data, the set of processing engines comprising:
a mapping module in a first configuration of the hardwired digital logic circuits to access in the memory, via the memory interface, at least some of the sequence of nucleotides in a selected read of the plurality of reads and the index of the one or more genetic reference sequences, and to map the selected read to one or more segments of the one or more genetic reference sequences based on the index to produce a mapped read;
an alignment module in a second configuration of the hardwired digital logic circuits to access the one or more genetic reference sequences from the memory via the memory interface to align the mapped read from the mapping module to one or more positions in the one or more segments of the one or more genetic reference sequences to produce an aligned read; and
a variant calling module in a third configuration of the hardwired digital logic circuits to access the aligned read and at least one of the genetic reference sequences, compare the sequence of nucleotides in the aligned reads to the sequence of nucleotides of the at least one genetic reference sequence, to determine one or more differences between the sequence of nucleotides in the aligned read and the sequence of nucleotides in the at least one genetic reference sequence, and to generate one or more variant calls representing the one or more differences; and
one or more of the plurality of physical electrical interconnects comprising an output from the integrated circuit for communicating result data from the mapping module and/or the alignment module and/or variant calling module.

### Claim 2 (depends on 1)

The system in accordance with claim 1, wherein the index of the one or more genetic reference sequences further comprises a hash table, and wherein the mapping module applies a hash function to the at least some of the sequence of nucleotides in the selected read to access the hash table of the index.

### Claim 3 (depends on 2)

The system in accordance with claim 2, wherein the integrated circuit and the memory are housed on an expansion card.

### Claim 4 (depends on 3)

The system in accordance with claim 3, wherein the expansion card is a peripheral component interconnect (PCI) card.

### Claim 5 (depends on 4)

The system in accordance with claim 4, wherein the system further comprises a sequencer, the sequencer having an electronic data source that provides digital signals representing the plurality of reads of genomic data.

### Claim 6 (depends on 5)

The system in accordance with claim 5, wherein the expansion card is physically integrated with the sequencer.

### Claim 7 (depends on 6)

The system in accordance with claim 6, further comprising a cloud computing cluster having one or more servers, wherein the integrated circuit is housed in at least one of the one or more servers.

### Claim 8 (depends on 7)

The system in accordance with claim 7, wherein the cloud computing cluster further comprises the electronic data source providing digital signals representing the plurality of reads of genomic data to the integrated circuit.

### Claim 9

A system for executing a sequence analysis pipeline on genetic sequence data, the system comprising:
a memory for storing one or more genetic reference sequences comprising one or more segments, an index of the one or more genetic reference sequences, and a plurality of reads of genomic data, each of the one or more genetic reference sequences and the plurality of reads of genomic data comprising a sequence of nucleotides; and
an integrated circuit formed of a set of 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 the memory, the digital logic circuits being arranged as a set of processing engines, each processing engine being formed of a subset of the digital logic circuits to perform at least one step in the sequence analysis pipeline on the plurality of reads of genomic data, the set of processing engines comprising:
an alignment module configured to access in the memory, via the memory interface, the one or more genetic reference sequences and a selected read of genomic data, to align the selected read of genomic data to one or more positions in the one or more segments of the one or more genetic reference sequences, to produce an aligned read, the aligned read comprising a sequence of nucleotides; and
a variant calling module configured to access in the memory, via the memory interface, the aligned read and at least one genetic reference sequence, compare the nucleotides in the aligned read to the nucleotides of the at least one genetic reference sequence to determine one or more differences between the sequences of nucleotides in the aligned read and the sequence of nucleotides in the at least one genetic reference sequence, and generate one or more variant calls representing the one or more differences; and
one or more of the plurality of physical electrical interconnects comprising an output from the integrated circuit for communicating result data from the alignment module and/or variant calling module.

### Claim 10 (depends on 9)

The system in accordance with claim 9, wherein the integrated circuit and the memory are housed on an expansion card.

### Claim 11 (depends on 10)

The system in accordance with claim 10, wherein the expansion card is a peripheral component interconnect (PCI) card.

### Claim 12 (depends on 11)

The system in accordance with claim 11, wherein the system further comprises a sequencer, the sequencer having an electronic data source that provides digital signals representing the plurality of reads of genomic data.

### Claim 13 (depends on 12)

The system in accordance with claim 12, wherein the expansion card is physically integrated with the sequencer.

### Claim 14 (depends on 9)

The system in accordance with claim 9, further comprising a cloud computing cluster having one or more servers, wherein the integrated circuit is housed in at least one of the one or more servers.

### Claim 15 (depends on 14)

The system in accordance with claim 14, wherein the cloud computing cluster further comprises the electronic data source providing digital signals representing the plurality of reads of genomic data to the integrated circuit.

### Claim 16

A system for executing a sequence analysis pipeline on genetic sequence data, the system comprising:
a memory for storing one or more genetic reference sequences, an index of the one or more genetic reference sequences, and a plurality of reads of genomic data, each of the genetic reference sequences and the plurality of reads of genomic data comprising a sequence of nucleotides; and
an integrated circuit formed of a set of 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 the memory, the hardwired digital logic circuits being arranged as a set of processing engines, each processing engine being formed of a subset of the hardwired digital logic circuits to perform at least one step in the sequence analysis pipeline on the plurality of reads of genomic data, the set of processing engines comprising:
a mapping module in a first configuration of the hardwired digital logic circuits to access in the memory, via the memory interface, at least some of the sequence of nucleotides in a selected read of the plurality of reads and the index of the one or more genetic reference sequences, and to map the selected read to one or more segments of the one or more genetic reference sequences based on the index to produce a mapped read; and
an alignment module in a second configuration of the hardwired digital logic circuits to access the one or more genetic reference sequences from the memory via the memory interface to align the mapped read from the mapping module to one or more positions in the one or more segments of the one or more genetic reference sequences to produce an aligned read;
a variant calling module connected with the integrated circuit to access the aligned read and at least one of the genetic reference sequences, compare the sequence of nucleotides in the aligned reads to the sequence of nucleotides of the at least one genetic reference sequence, to determine one or more differences between the sequence of nucleotides in the aligned read and the sequence of nucleotides in the at least one genetic reference sequence, and to generate one or more variant calls representing the one or more differences; and
one or more of the plurality of physical electrical interconnects comprising an output from the integrated circuit for communicating result data from the mapping module and/or the alignment module and/or variant calling module.

### Claim 17 (depends on 16)

The system in accordance with claim 16, wherein the integrated circuit and the memory are housed on an expansion card.

### Claim 18 (depends on 17)

The system in accordance with claim 17, wherein the expansion card is a peripheral component interconnect (PCI) card.

### Claim 19 (depends on 18)

The system in accordance with claim 18, wherein the system further comprises a sequencer, the sequencer having an electronic data source that provides digital signals representing the plurality of reads of genomic data.

### Claim 20 (depends on 16)

The system in accordance with claim 16, further comprising a cloud computing cluster having one or more servers, wherein the integrated circuit is housed in at least one of the one or more servers.

### Claim 21 (depends on 20)

The system in accordance with claim 20, wherein the cloud computing cluster further comprises the electronic data source providing digital signals representing the plurality of reads of genomic data to the integrated circuit.

### Claim 22 (depends on 16)

The system in accordance with claim 16, wherein the integrated circuit comprises a graphics processing unit (GPU).

### Claim 23 (depends on 16)

The system in accordance with claim 16, wherein the integrated circuit comprises a field programmable gate array (FPGA) or an application specific integrated circuit (ASIC).

### Claim 24

An integrated circuit for executing a portion of a sequence analysis pipeline on a plurality of reads of genomic data using genetic reference sequence data, where each read of the plurality of reads of genomic data and the genetic reference sequence data represent a sequence of nucleotides, the integrated circuit comprising:
a memory storing the plurality of reads of genomic data and the genetic reference sequence data;
a field programmable gate array (FPGA), the FPGA being formed of a set of hardwired digital logic circuits, the hardwired digital logic circuits being interconnected by a plurality of physical electrical interconnects, one or more of the plurality of physical electrical interconnects comprising a memory interface to access the memory, the hardwired digital logic circuits being 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 plurality of reads of genomic data, the set of processing engines comprising a variant calling module configured to access one or more reads of the plurality of reads of genomic data and the genetic reference sequence data, compare the sequence of nucleotides in the one or more reads of genomic data to the sequence of nucleotides of the genetic reference sequence data to determine one or more differences between the sequence of nucleotides in the reads of genomic data and the sequence of nucleotides in the genetic reference sequence data, and generate one or more variant calls representing the one or more differences.

### Claim 25 (depends on 24)

The system in accordance with claim 24, wherein the FPGA and the memory are housed on an expansion card.

### Claim 26 (depends on 25)

The system in accordance with claim 25, wherein the expansion card is a peripheral component interconnect (PCI) card.

### Claim 27 (depends on 26)

The system in accordance with claim 26, wherein the system further comprises a sequencer, the sequencer having an electronic data source that provides digital signals representing the plurality of reads of genomic data.

### Claim 28 (depends on 24)

The system in accordance with claim 24, further comprising a cloud computing cluster having one or more servers, wherein the FPGA is housed in at least one of the one or more servers.

### Claim 29 (depends on 28)

The system in accordance with claim 28, wherein the cloud computing cluster further comprises an electronic data source providing digital signals representing the plurality of reads of genomic data to the integrated circuit.

### Claim 30 (depends on 29)

The system in accordance with claim 29, wherein the electronic data source is a sequencer.