# US 2020/0399701 A1 · Systems and methods for using density of single nucleotide variations for the verification of copy number variations in human embryos

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- Number: US 2020/0399701 A1
- Document ID: US20200399701A1
- Status: Published application
- Kind: A1
- Application number: 16/906,441
- Filed: 2020-06-19
- Published: 2020-12-24
- Earliest claimed: 2019-06-21
- Assignees: CooperSurgical, Inc.
- Applicants: CooperSurgical, Inc.
- Inventors: John BURKE; Brian RHEES; Joshua David BLAZEK; Michael Jon LARGE
- Web page: https://patentgrep.com/patent/US20200399701A1

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- 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
- C12Q 2600/156: Polymorphic or mutational markers
- G16B 20/10: Ploidy or copy number detection
- G16B 20/20: Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
- G16B 40/20: Supervised data analysis
- G16B 40/30: Unsupervised data analysis
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY

## Abstract

A method for verifying a genomic variant region in an embryo, is disclosed. Embryo sequencing data is received by one or more processors. The received embryo sequencing data is aligned to a reference genome, by the one or more processors. A genomic variant region is identified in the aligned embryo sequencing data, by the one or more processors. A number of single nucleotide variants (SNVs) is counted in the identified genomic variant region, by the one or more processors. The counted number of SNVs in the identified genomic variant region is normalized against a baseline count of SNVs for a reference region corresponding to the identified genomic variant region to generate a normalized SNV density for the genomic variant region, by the one or more processors. The identified genomic variant region is verified, by the one or more processors, if the normalized SNV density in the identified genomic variant region satisfies a tolerance criterion.

## Claims

### Claim 1

A method for verifying a genomic variant region in an embryo, comprising:
receiving, by one or more processors, embryo sequencing data;
aligning, by the one or more processors, the received embryo sequencing data to a reference genome;
identifying, by the one or more processors, a genomic variant region in the aligned embryo sequencing data;
counting, by the one or more processors, a number of single nucleotide variants (SNVs) in the identified genomic variant region;
normalizing, by the one or more processors, the counted number of SNVs in the identified genomic variant region against a baseline count of SNVs for a reference region corresponding to the identified genomic variant region to generate a normalized SNV density for the genomic variant region; and
verifying, by the one or more processors, the identified genomic variant region, if the normalized SNV density in the identified genomic variant region satisfies a tolerance criterion.

### Claim 2 (depends on 1)

The method of claim 1, wherein the genomic variant region is a copy number variation region.

### Claim 3 (depends on 1)

The method of claim 1, wherein the genomic variant region is an aneuploidy region.

### Claim 4 (depends on 1)

The method of claim 1, wherein the genomic variant region is a polyploidy region.

### Claim 5 (depends on 1)

The method of claim 1, wherein the reference region is an exact length of the identified genomic variant region.

### Claim 6 (depends on 1)

The method of claim 1, wherein the reference region is derived from an euploid sample.

### Claim 7 (depends on 1)

The method of claim 1, wherein the tolerance criterion is an expected SNV density for a reference region derived from an euploid embryo.

### Claim 8 (depends on 7)

The method of claim 7, wherein the identified genomic variant region is verified if the normalized SNV density of the identified genomic variant region is greater or lesser than a pre-set confidence interval of the expected SNV density for the reference region.

### Claim 9 (depends on 8)

The method of claim 8, wherein the lower pre-set confidence interval is 95%.

### Claim 10 (depends on 1)

The method of claim 1, wherein the tolerance criterion is an expected SNV density for a reference region derived from a mosaic embryo.

### Claim 11 (depends on 10)

The method of claim 10, wherein the identified genomic variant region is verified if the normalized SNV density of the identified genomic variant region is above a pre-set confidence interval of the expected SNV density for the reference region.

### Claim 12 (depends on 11)

The method of claim 11, wherein the pre-set confidence interval 95%.

### Claim 13 (depends on 1)

The method of claim 1, wherein the tolerance criterion is a preset variance number of SNVs over or under a baseline count of SNVs for the reference region.

### Claim 14

A non-transitory computer-readable medium storing computer instruction for verifying a genomic variant region in an embryo, comprising:
receiving, by one or more processors, embryo sequencing data;
aligning, by the one or more processors, the received embryo sequencing data to a reference genome;
identifying, by the one or more processors, a genomic variant region in the aligned embryo sequencing data;
counting, by the one or more processors, a number of single nucleotide variants (SNVs) in the identified genomic variant region;
normalizing, by the one or more processors, the counted number of SNVs in the identified genomic variant region against a baseline count of SNVs for a reference region corresponding to the identified genomic variant region to generate a normalized SNV density for the genomic variant region; and
verifying, by the one or more processors, the identified genomic variant region, if the normalized SNV density in the identified genomic variant region satisfies a tolerance criterion.

### Claim 15

A system for verifying a genomic variant region in an embryo, comprising:
a data store for storing embryo sequencing data;
a computing device communicatively connected to the data store, comprising,
an alignment engine configured to receive and align the embryo sequencing data against a reference genome,
a genomic variant caller configured to identify a genomic variant region in the aligned embryo sequencing data, and
a verification engine configured to:
count a number of single nucleotide variants (SNVs) in the identified genomic variant region and normalize the SNVs count in the identified genomic variant region against a baseline count of SNVs for a reference region corresponding to the identified genomic variant region to generate a normalized SNV density for the identified genomic variant region, and
verify the identified genomic variant region if the normalized SNV density in the identified genomic variant region satisfies a tolerance criterion; and
a display communicatively connected to the computing device and configured to display a report containing genomic variant region results from the verification engine.

### Claim 16 (depends on 15)

The system of claim 15, wherein the genomic variant region is a copy number variation region.

### Claim 17 (depends on 15)

The system of claim 15, wherein the genomic variant region is an aneuploidy region.

### Claim 18 (depends on 15)

The system of claim 15, wherein the genomic variant region is a polyploidy region.

### Claim 19 (depends on 15)

The system of claim 15, wherein the reference region is an exact length of the identified genomic variant region.

### Claim 20 (depends on 15)

The system of claim 15, wherein the reference region is derived from an euploid sample.

### Claim 21 (depends on 15)

The system of claim 15, wherein the tolerance criterion is an expected SNV density for a reference region derived from an euploid embryo.

### Claim 22 (depends on 21)

The system of claim 21, wherein the identified genomic variant region is verified if the normalized SNV density of the identified genomic variant region is greater or lesser than a pre-set confidence interval of the expected SNV density for the reference region.

### Claim 23 (depends on 22)

The system of claim 22, wherein the lower pre-set confidence interval is 95%.

### Claim 24 (depends on 15)

The system of claim 15, wherein the tolerance criterion is an expected SNV density for a reference region derived from a mosaic embryo.

### Claim 25 (depends on 24)

The system of claim 24, wherein the identified genomic variant region is verified if the normalized SNV density of the identified genomic variant region is above a pre-set confidence interval of the expected SNV density for the reference region.

### Claim 26 (depends on 25)

The system of claim 25, wherein the pre-set confidence interval 95%.

### Claim 27 (depends on 15)

The system of claim 15, wherein the tolerance criterion is a preset variance number of SNVs over or under a baseline count of SNVs for the reference region.