# US 2016/0259882 A1 · Method and system for estimating genomic health

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- Number: US 2016/0259882 A1
- Document ID: US20160259882A1
- Status: Published application
- Kind: A1
- Application number: 15/034,459
- Filed: 2015-11-04
- Published: 2016-09-08
- Earliest claimed: 2013-11-04
- Assignees: Medisapiens Oy
- Applicants: Medisapiens Oy
- Inventors: Kalle OJALA; Sami KILPINEN
- Web page: https://patentgrep.com/patent/US20160259882A1

## CPC

- G16B 20/00: ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY

## Abstract

Techniques for estimating genomic health of a sexually reproducing organism. Stored information on hereditary diseases is used to determine a risk for each disease for allele combinations in a specimen, and to determine a degree of severity, wherein the risk and severity are commensurate. For each hereditary disease a risk is determined for the specimen to have the disease from the from the specimen's genotype; a default risk is assigned, if the hereditary disease exhibits Mendelian inheritance and if the specimen is a carrier of the disease. The risk for the hereditary disease is multiplied by an expansive function (e.g., square) of the severity. A statistically representative value of the multiplied risks is calculated, replacing zero values with marginal finite values if the expansive function cannot process zero values.

## Claims

### Claim at position 1

1-9. (canceled)

### Claim 10

A method comprising:
estimating overall genomic health of a sexually reproducing organism or its virtual presentation, wherein said estimating comprises:
in a set-up phase:
storing information on a plurality of hereditary diseases potentially affecting a species of the sexually reproducing organism;
for each hereditary disease in the plurality of hereditary diseases:
determining a risk for that disease for a plurality of allele combinations in a specimen of the species;
determining a degree of severity in the species;
wherein the risk and severity are commensurate;
in a specimen-specific phase:
for each hereditary disease:
determining a risk for the specimen to have the hereditary disease from the from the specimen's genotype;
assigning a default risk which is between 0.2 and 0.8 of the range of values for the risk, if the hereditary disease exhibits Mendelian inheritance and if the specimen is a carrier of the disease;
multiplying the risk for the hereditary disease by an expansive function of the severity; and
calculating a statistically representative value of the multiplied risks.

### Claim 11 (depends on 10)

The method of claim 10, further comprising:
calculating a degree of heterozygosity as a portion of the specimen's loci that are heterozygous, wherein the degree of heterozygosity is commensurate with the statistically representative value of the multiplied risks; and
calculating a combined genomic health index as a combination of the statistically representative value of the multiplied risks and the degree of heterozygosity.

### Claim 12 (depends on 10)

The method of claim 10, further comprising:
applying a compressive scaling function on the calculated statistically representative value, replacing zero values with marginal finite values if the compressive scaling function cannot process zero values;
wherein the compressive scaling function is scaled in such a manner that a specimen free from hereditary diseases obtains a base value of 10N, wherein N is an integer, and the specimen known to have highest statistically representative value of the multiplied risks obtains a value of k·10N, wherein k=0.3−0.7.

### Claim 13 (depends on 2, 11)

The method of claim 11, wherein the sexually reproducing organism is a non-human organism, the method further comprising:
selecting a pair of potential parent specimens with known genotypes;
calculating possible genotypes for each locus for several virtual descendants, plus portion of descendants having each of the calculated genotypes;
estimating an average degree of heterozygosity for the virtual descendants plus the portions of the virtual descendants that, for each inherited disease, are healthy, carriers, or have the disease;
creating a plurality of virtual descendants;
utilizing genotype frequencies from the calculation of genotypes to populate genotype data of the virtual descendants, by using genotype frequencies estimated for real descendants;
applying the method according to claim 2 to the virtual descendants, to calculate a combined genomic health index for each virtual descendant from the average heterozygosity and the populated genotype data of the virtual descendant;
calculating a second statistically representative value from the calculated combined genomic health indices for the virtual descendants; and
calculating a breeding score for the pair of potential parent specimens, wherein the breeding score is at least partially based on a detected portion of combined genomic health indices of real specimens that are below the second statistically representative value calculated for the virtual descendants.

### Claim 14 (depends on 13)

The method of claim 13, wherein the calculating possible genotypes plus portion of descendants having the calculated genotypes comprises adjusting probabilities to inherited genes based on closeness between genes.

### Claim 15 (depends on 10)

The method of claim 10, wherein the sexually reproducing organism is an animal.

### Claim 16 (depends on 15)

The method of claim 15, wherein the animal is a non-human animal.

### Claim 17 (depends on 11)

The method of claim 11, wherein the sexually reproducing organism is an animal.

### Claim 18 (depends on 17)

The method of claim 17, wherein the animal is a non-human animal.

### Claim 19 (depends on 12)

The method of claim 12, wherein the sexually reproducing organism is an animal.

### Claim 20 (depends on 19)

The method of claim 19, wherein the animal is a non-human animal.

### Claim 21 (depends on 13)

The method of claim 13, wherein the sexually reproducing organism is an animal.

### Claim 22 (depends on 21)

The method of claim 21, wherein the animal is a non-human animal.

### Claim 23 (depends on 14)

The method of claim 14, wherein the sexually reproducing organism is an animal.

### Claim 24 (depends on 23)

The method of claim 23, wherein the animal is a non-human animal.

### Claim 25

A data processing system comprising:
a memory system for storing program code instructions and data;
a processing system including at least one processing unit, wherein the processing system executes at least a portion of the program code instructions and processes the data;
an interface for receiving data representative of a genotype of a each of a plurality of sexually reproducing organims;
wherein the memory system stores program code instructions that, when executed by the processing system, instruct the processing system to estimate an overall genomic health of a sexually reproducing organism or its virtual presentation, wherein said estimating comprises:
in a set-up phase:
storing information on a plurality of hereditary diseases potentially affecting a species of a sexually reproducing organism;
for each hereditary disease in the plurality of hereditary diseases:
determining a risk for that disease for a plurality of allele combinations in a specimen of the species;
determining a degree of severity in the species;
wherein the risk and severity are commensurate;
in a specimen-specific phase:
for each hereditary disease:
determining a risk for the specimen to have the hereditary disease from the from the specimen's genotype;
assigning a default risk which is between 0.2 and 0.8 of the range of values for the risk, if the hereditary disease exhibits Mendelian inheritance and if the specimen is a carrier of the disease;
multiplying the risk for the hereditary disease by an expansive function of the severity; and
calculating a statistically representative value of the multiplied risks.

### Claim 26 (depends on 25)

The system of claim 25, wherein the estimating further comprises:
calculating a degree of heterozygosity as a portion of the specimen's loci that are heterozygous, wherein the degree of heterozygosity is commensurate with the statistically representative value of the multiplied risks; and
calculating a combined genomic health index as a combination of the statistically representative value of the multiplied risks and the degree of heterozygosity.

### Claim 27 (depends on 25)

The system of claim 25, wherein the estimating further comprises:
applying a compressive scaling function on the calculated statistically representative value, replacing zero values with marginal finite values if the compressive scaling function cannot process zero values;
wherein the compressive scaling function is scaled in such a manner that a specimen free from hereditary diseases obtains a base value of 10N, wherein N is an integer, and the specimen known to have highest statistically representative value of the multiplied risks obtains a value of k·10N, wherein k=0.3−0.7.

### Claim 28 (depends on 2, 27)

The system of claim 27, wherein the sexually reproducing organism is a non-human organism, and the estimating further comprises:
selecting a pair of potential parent specimens with known genotypes;
calculating possible genotypes for each locus for several virtual descendants, plus portion of descendants having each of the calculated genotypes;
estimating an average degree of heterozygosity for the virtual descendants plus the portions of the virtual descendants that, for each inherited disease, are healthy, carriers, or have the disease;
creating a plurality of virtual descendants;
utilizing genotype frequencies from the calculation of genotypes to populate genotype data of the virtual descendants, by using genotype frequencies estimated for real descendants;
applying the method according to claim 2 to the virtual descendants, to calculate a combined genomic health index for each virtual descendant from the average heterozygosity and the populated genotype data of the virtual descendant;
calculating a second statistically representative value from the calculated combined genomic health indices for the virtual descendants; and
calculating a breeding score for the pair of potential parent specimens, wherein the breeding score is at least partially based on a detected portion of combined genomic health indices of real specimens that are below the second statistically representative value calculated for the virtual descendants.

### Claim 29 (depends on 28)

The system of claim 28, wherein the calculating possible genotypes plus portion of descendants having the calculated genotypes comprises adjusting probabilities to inherited genes based on closeness between genes.

### Claim 30 (depends on 25)

The system of claim 25, wherein the sexually reproducing organism is an animal.

### Claim 31 (depends on 31)

The system of claim 31, wherein the animal is a non-human animal.

### Claim 32

A tangible non-transitory program carrier comprising program code instructions for a data processing system, wherein the data processing system comprises: a memory system for storing program code instructions and data; a processing system including at least one processing unit, wherein the processing system executes at least a portion of the program code instructions and processes the data; and an interface for receiving data representative of a genotype of a each of a plurality of sexually reproducing organims;
wherein the tangible non-transitory program carrier comprises program code instructions that, when executed by the processing system, instruct the processing system to carry out the method comprising:
estimating overall genomic health of a sexually reproducing organism or its virtual presentation, wherein said estimating comprises:
in a set-up phase:
storing information on a plurality of hereditary diseases potentially affecting a species of the sexually reproducing organism;
for each hereditary disease in the plurality of hereditary diseases:
determining a risk for that disease for a plurality of allele combinations in a specimen of the species;
determining a degree of severity in the species;
wherein the risk and severity are commensurate;
in a specimen-specific phase:
for each hereditary disease:
determining a risk for the specimen to have the hereditary disease from the from the specimen's genotype;
assigning a default risk which is between 0.2 and 0.8 of the range of values for the risk, if the hereditary disease exhibits Mendelian inheritance and if the specimen is a carrier of the disease;
multiplying the risk for the hereditary disease by an expansive function of the severity; and
calculating a statistically representative value of the multiplied risks.