Methods and systems for determining and displaying pedigrees

Abstract

The disclosed embodiments concern methods, apparatus, systems and computer program products for determining and displaying pedigrees based on IBD data. Some implementations use a probabilistic relationship model to obtain various likelihoods of various potential relationships based on pairwise IBD data, and pairwise age data. Some implementations build large pedigrees by combining smaller pedigrees. Some implementations display pedigree graphs with various features that are informative and easy to understand.

1 . A method, implemented using a computer system that includes one or more processors and system memory, for determining pedigree relationships among a plurality of genetically related individuals, the method comprising:
 a) identifying, among the plurality of genetically related individuals, a closest relative of a starting individual using genetic data of the plurality of genetically related individuals;   b) applying pairwise Identity-by-Descent (IBD) data and pairwise age data of the starting individual and the closest relative to a probabilistic relationship model to obtain various likelihoods of various potential relationships between the starting individual and the closest relative;   c) selecting one or more potential relationships between the starting individual and the closest relative that have relationship likelihoods meeting a relationship criterion, and forming a pedigree from each of the one or more potential relationships;   d) identifying, among genetically related individuals not included in pedigrees already formed, a closest relative of any individual already in a pedigree;   e) applying pairwise IBD data and pairwise age data of the closest relative and the individual already in the pedigree to the probabilistic relationship model to obtain various likelihoods of various potential relationships between the closest relative and the individual already in the pedigree;
 selecting one or more potential relationships between the closest relative and the individual already in the pedigree that have relationship likelihoods meeting the relationship criterion, and adding each of the one or more potential relationships to each pedigree already formed to grow each pedigree into one or more growing pedigrees; 
   f) selecting growing pedigrees that have pedigree likelihoods meeting a pedigree criterion as the pedigrees already formed; and   g) repeating (1d)-(1g) one or more times,   
       wherein (1a)-(1h) are performed by the computer system. 
     
     
         2 . The method of  claim 1 , wherein the pairwise IBD data comprise a length of IBD segments. 
     
     
         3 . The method of  claim 2 , wherein the lengths of IBD segments comprise a length of full IBD segments and/or a length of half IBD segments. 
     
     
         4 . The method of  claim 1 , wherein the pairwise IBD data comprise a number of IBD segments. 
     
     
         5 . The method of  claim 4 , wherein the number of IBD segments comprise a number of full IBD segments and/or a number of half IBD segments. 
     
     
         6 . The method of  claim 1 , wherein the probabilistic relationship model is a machine-learning model. 
     
     
         7 . The method of  claim 1 , wherein the probabilistic relationship model models the probability distribution of the pairwise IBD data for each relationship and/or the probability distribution of the pairwise age data for each relationship as a Gaussian distribution, a Poisson distribution, or an exponential distribution. 
     
     
         8 . The method of  claim 1 , further comprising: storing into a database or retrieving from a database relationship data of a pedigree having the highest pedigree likelihood among the growing pedigrees selected in (1g). 
     
     
         9 . The method of  claim 8 , further comprising:
 a) generating a pedigree graph using the relationship data of the pedigree having the highest pedigree likelihood; and   b) displaying the pedigree graph on a display device.   
     
     
         10 - 19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein pairwise IBD data between two individuals are used to determine how closely related the two individuals are. 
     
     
         21 . The method of  claim 1 , wherein the relationship criterion is a ratio of an instant relationship likelihood over a maximum relationship likelihood being larger than a value c. 
     
     
         22 . The method of  claim 1 , wherein the pedigree criterion is a ratio of an instant pedigree likelihood over a maximum pedigree likelihood being larger than a specific value d. 
     
     
         23 . The method of  claim 1 , wherein (1h) comprises repeating (1d)-(1g) until all individuals of the plurality of genetically related individuals have been identified as a closest relative or excluded from the pedigree. 
     
     
         24 . The method of  claim 1 , further comprising:
 b) identifying two pedigrees from among a plurality of pedigrees constructed using operations (1a)-(1h), the two pedigrees being a genealogically closest pair of pedigrees among all pairs in the plurality pedigrees.   
     
     
         25 . The method of  claim 24 , wherein in operation (24c) a genealogical similarity between two pedigrees that are the genealogically closest pair of pedigrees is measured as a union over all IBD segments shared between an individual in a first pedigree in the genealogically closest pair of pedigrees and an individual in a second pedigree in the genealogically closest pair of pedigrees. 
     
     
         26 . The method of  claim 24  or  25 , further comprising:
 c) combining the two pedigrees identified in operation (24c) into a combined pedigree. 
 
     
     
         27 . The method of  claim 26 , further comprising:
 d) repeating operations (24c) and (26d) to agglomerate a plurality of pedigrees into a large pedigree.   
     
     
         28 . The method of  claim 26 , wherein in operation (26d) the two pedigrees are combined by:
 a) identifying a first set of individuals in a first pedigree who share IBD with individuals in a second pedigree;   b) identifying a second set of individuals in the second pedigree who share IBD with individuals in the first pedigree;   c) identifying a common ancestor of the first set of individuals;   d) identifying a common ancestor of the second set of individuals;   e) inferring a degree of relatedness between the common ancestor of the first set and the common ancestor of the second set; and   f) connecting the two common ancestors by an inferred degree of relatedness between the common ancestors.   
     
     
         29 - 35 . (canceled) 
     
     
         36 . A method, implemented using a computer system that includes one or more processors and system memory, for combining two or more pedigrees into a larger pedigree, the method comprising:
 a) identifying a first pedigree and a second pedigree from among a plurality of pedigrees, the two pedigrees being a genealogically closest pair of pedigrees among all pairs in the plurality pedigrees;   b) identifying a first set of individuals in the first pedigree who share IBD with individuals in the second pedigree;   c) identifying a second set of individuals in the second pedigree who share IBD with individuals in the first pedigree;   d) identifying a common ancestor of the first set of individuals;   e) identifying a common ancestor of the second set of individuals;   f) inferring a degree of relatedness between the common ancestor of the first set and the common ancestor of the second set; and   g) connecting the two common ancestors by an inferred degree of relatedness between the common ancestors to form a larger pedigree.   
     
     
         37 - 99 . (canceled) 
     
     
         100 . A method, implemented using a computer system comprising a processor and system memory, of generating pedigree graphs, the method comprising:
 a) receiving, by the processor, annotation data to annotate one or more ungenotyped nodes of a first pedigree graph that depicts relationships among a first plurality of individuals, wherein the first pedigree graph comprises a plurality of genotyped nodes and one or more ungenotyped nodes, each node representing an individual, a genotyped node represents an individual whose genetic data have been used to determine the pedigree relationships depicted by the pedigree graph, and an ungenotyped node represents an individual whose genetic data have not been used to determine the pedigree relationships depicted by the pedigree graph,   b) generating, using the processor, a second pedigree graph that depicts relationships among a second plurality of individuals, wherein the second pedigree graph comprises a plurality of genotyped nodes and one or more ungenotyped nodes, each node representing an individual;   c) matching, using the processor, one or more annotated, ungenotyped nodes of the first pedigree graph respectively with one or more corresponding nodes of the second pedigree graph;   d) annotating, using the processor, the one or more corresponding nodes of the second pedigree graph respectively using annotation data of their matching nodes of the first pedigree graph.   
     
     
         101 - 119 . (canceled)