Methods for analyzing genotypes

Patent metadata

Field	Value
Publication number	US-2016283484-A1
Application number	US-201615083058-A
Country	US
Kind code	A1
Filing date	Mar 28, 2016
Priority date	Oct 3, 2013
Publication date	Sep 29, 2016
Grant date	—

Abstract

The disclosure provides methods and systems for analyzing genotype data. In some embodiments, a computer-implemented method comprises receiving data relating to one or more phenotypes of a subject or family members thereof, and ranking genes based on their association score with one or more phenotypes. Next, an output of the data is generated, the output comprising a comparison of the data based on the association score. The comparison can be in at least one of numeric and graphic form.

First claim

1 . A computer-implemented method, comprising:
a. receiving data relating to one or more phenotypes of a subject or family members of the subject; b. using a programmed computer processor, ranking a plurality of genes based at least in part on their association score with the one or more phenotypes; and c. generating a numeric or graphical output with at least a subset of the plurality of genes ranked based on their association score with the one or more phenotypes.

2 . A computer-implemented method, comprising:
a. receiving data relating to one or more genotypes of a subject or family members of the subject; b. receiving data relating to one or more phenotypes of the subject or family members of the subject; c. using a programmed computer processor, ranking a plurality of genes of the one or more genotypes using an inheritance pattern score that is based on allowed genotypes with respect to the one or more phenotypes; and d. generating a numeric or graphical output with at least a subset of the plurality of genes ranked based on the inheritance pattern score.

3 . A computer-implemented method, comprising:
a. receiving data relating to one or more phenotypes of a subject or family members of the subject; b. receiving data relating to one or more genotypes of the subject or family members of the subject; c. using a programmed computer processor, ranking a plurality of genes based at least in part on their association score with the one or more phenotypes; d. using the programmed computer processor, ranking the plurality of genes of the one or more genotypes using an inheritance pattern score that is based on allowed genotypes; and e. generating an output with at least a subset of the plurality of genes ranked based on the association score and inheritance pattern score.

4 . The method of claim 3 , wherein the one or more phenotypes comprise one or more diseases, traits, symptoms, laboratory values, diagnoses, behaviors, conditions, or a combination thereof.

5 . The method of claim 3 , wherein the association score comprises the association of one or more genes with one or more of: genes, proteins, RNAs, pathognomonic features, clinical features, diseases, traits, symptoms, laboratory values, diagnoses, behaviors, conditions, differential diagnoses, prognoses, genetic history, familial information, hereditary information, human phenotypes, non-human phenotypes, genotypes, genomes, exomes, pathways, disease ontology, phenotype ontology, and gene ontology, or any combination thereof.

6 .- 11 . (canceled)

12 . The method of claim 3 , wherein the association score is related to the number of clinical features and/or diagnoses associated with the plurality of genes.

13 . (canceled)

14 . The method of claim 12 , wherein the association score is a weighted score based on (i) familial and/or hereditary information; (ii) specificity of a clinical feature-to-gene relationship; and/or (iii) reciprocity of clinical features and/or diseases associated with the genes.

15 .- 16 . (canceled)

17 . The method of claim 3 , wherein the output comprises a comparison of the data based on the association score that identifies the likelihood of one or more of: causative genes, neutral genes and non-causative genes.

18 . (canceled)

19 . The method of claim 3 , wherein the data comprises two or more genotypes and wherein the ranking comprises ranking the two or more genotypes.

20 . The method of claim 19 , wherein the two or more genotypes are ranked based on the inheritance pattern score.

21 . The method of claim 20 , wherein the inheritance pattern score is at least partially based on a likelihood of the genotype to explain a particular inheritance pattern, a segregation pattern, or a combination thereof.

22 . The method of claim 3 , wherein the output is based on data from one or more databases that comprise one or more medical records, clinical notes, genomic databases, biomedical databases, clinical databases, scientific databases, disease databases, pathway and network databases, regulatory region databases, and biomarker databases, or any combination thereof.

23 .- 25 . (canceled)

26 . The method of claim 3 , wherein the ranking is indicative of the likelihood of a genotype variant to be associated with a disease.

27 .- 29 . (canceled)

30 . The method of claim 3 , further comprising generating the association score by:
a. generating, with the aid of a computer processor, a correlation between (i) one or more genes and (ii) a given phenotype or associated clinical feature among the one or more phenotypes or associated clinical features, to provide one or more sets of genes stored in a memory location; and b. designating each of the one or more sets of genes as (i) likely to be a causative of a given phenotype or associated clinical feature among the one or more phenotypes or associated clinical features if the given set of genes is associated with a plurality of search criteria correlated with the given phenotype or associated clinical feature, (ii) neutral if the given set of genes is not associated with any phenotype or clinical feature, or (iii) unlikely to be causative of the given phenotype or clinical feature if the set of genes is associated with a plurality of phenotypes or associated clinical features that do not include the given phenotype or associated clinical feature.

31 . (canceled)

32 . The method of claim 30 , further comprising intersecting the one or more sets of genes with one or more variants of an individual or a family of the individual having a phenotype or associated clinical feature that is caused by, or is suspected to be caused by, one or more genetic variants, wherein the one or more genetic variants are identified using a genetic sequencing system.

33 .- 34 . (canceled)

35 . The method of claim 3 , further comprising providing a diagnosis and/or treatment for the subject based on the output.

36 . (canceled)

37 . The method of claim 3 , wherein the inheritance pattern score is generated by generating, with the aid of a computer processor, one or more expected genotypes for all members of a family of the subject, wherein the one or more expected genotypes are generated for potential inheritance patterns of the family.

38 . The method of claim 37 , further comprising ranking the one or more expected genotypes based on a likelihood of an individual genotype among the one or more expected genotypes to provide a given inheritance pattern among the potential inheritance patterns.

39 . The method of claim 38 , further comprising analyzing a segregation pattern of a phenotype among the one or more phenotypes in the family, determining a most likely inheritance pattern based on the segregation pattern of the phenotype and ranking the one or more expected genotypes based on the most likely inheritance pattern.

40 .- 41 . (canceled)

42 . The method of claim 39 , further comprising identifying, with the aid of a genetic sequencing system, one or more genotypes of variants for one or more members of the family, assigning a rank to each genotype of a given variant based on the rank of the corresponding genotype in the one or more expected genotypes and using a programmed computer processor to correlate the genotype of a given variant that has a highest rank with at least a subset of

Assignees

• Personalis Inc

Inventors

• Chandratillake Gemma L
• Garcia Sarah K
• Chen Richard
• Clark Michael James

Classifications

• G06F17/30554

  Physics · mapped topic

• G06F19/18

  Physics · mapped topic

• G06F19/28

  Physics · mapped topic

• G06F17/3053 Primary

  Physics · mapped topic

• G16B20/00 Primary

  ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations · CPC title