IBD-Groupon: an efficient method for detecting group-wise identity-by-descent regions simultaneously in multiple individuals based on pairwise IBD relationships

He, Dan

doi:10.1093/bioinformatics/btt237

Cited by 16 publications

(15 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…• how to efficiently identify pairs of segments in individuals which were inherited from a recent common ancestry [7,14,19] • predicting haplotypes or the sequence of alleles on a chromosome from the genotype information which mixes the two chromosomes [15,3,16,2,20,56] • identifying the population origin of each region of an individual's genome for individuals who are admixed or a mixture of multiple ancestral populations [51,47].…”

Section: Box 2: Computational Problems In Geneticsmentioning

confidence: 99%

Discovering genes involved in disease and the mystery of missing heritability

Eskin

2015

Commun. ACM

View full text Add to dashboard Cite

It has been known for many decades that genetic differences among individuals account for a substantial portion of trait differences. Only recently has technology been developed to cost effectively measure genetic differences among individuals which creates the possibility of developing models that can predict disease related traits from an individual's genetics. These models are a key component of personalized medicine and developing such models raise many computational challenges which provide important opportunities for Computer Scientists to make contributions toward human health.

show abstract

Section: Box 2: Computational Problems In Geneticsmentioning

confidence: 99%

Discovering genes involved in disease and the mystery of missing heritability

Eskin

2015

Commun. ACM

View full text Add to dashboard Cite

show abstract

“…IBD calls can be made from IBD probabilities using a thresholding approach in which all probabilities exceeding a threshold are output as IBD. Alternatively, methods such as DASH [ 12 ], EMI [ 19 ], and IBD-Groupon [ 18 ] leverage the clique nature of IBD graphs to output cliques over a region as opposed to IBD pairs. The choice of IBD calling method is a function of the objective of the study.…”

Section: Resultsmentioning

confidence: 99%

“…Since these methods consider pairs of individuals independently, they are computationally efficient at the genome-wide scale. However, they do not exploit the clique structure of true IBD segments [ 12 , 18 ], and lack power relative to multiway approaches for smaller IBD segments [ 15 , 18 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…In thresholding approaches, all segments exceeding a probability cutoff are output as IBD. Recent clique-calling methods such as DASH [ 12 ], IBD-Groupon [ 18 ], and Efficient Multiple-IBD (EMI) algorithm [ 19 ] have been proposed to output cliques of IBD. The probabilities output by PIGS can be used as input to either thresholding or clique-based methods and we discuss the relative merits of these approaches in detail below (see Results).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PIGS: improved estimates of identity-by-descent probabilities by probabilistic IBD graph sampling

et al. 2015

View full text Add to dashboard Cite

Identifying segments in the genome of different individuals that are identical-by-descent (IBD) is a fundamental element of genetics. IBD data is used for numerous applications including demographic inference, heritability estimation, and mapping disease loci. Simultaneous detection of IBD over multiple haplotypes has proven to be computationally difficult. To overcome this, many state of the art methods estimate the probability of IBD between each pair of haplotypes separately. While computationally efficient, these methods fail to leverage the clique structure of IBD resulting in less powerful IBD identification, especially for small IBD segments.We develop a hybrid approach (PIGS), which combines the computational efficiency of pairwise methods with the power of multiway methods. It leverages the IBD graph structure to compute the probability of IBD conditional on all pairwise estimates simultaneously. We show via extensive simulations and analysis of real data that our method produces a substantial increase in the number of identified small IBD segments.

show abstract

“…Genotypes for each genotyped individual were obtained from Illumina Omni 2.5M SNP arrays, and then phased into haplotypes using SHAPEIT2 [12]. We identify IBD segments between pairs of genotyped individuals using GERMLINE [17], although IBD-Groupon for detecting IBD in groups could be used instead [19]. For each IBD segment I, we combine pairs until we obtain a cohort of individuals who share this segment, C 2 {2, n}.…”

Section: ) Place Ibd Segments In Ancestorsmentioning

confidence: 99%

Ancestral Haplotype Reconstruction in Endogamous Populations using Identity-By-Descent

Finke

Kourakos

Brown

et al. 2020

Preprint

View full text Add to dashboard Cite

In this work we develop a novel algorithm for reconstructing the genomes of ancestral individuals, given genotype or sequence data from contemporary individuals and an extended pedigree of family relationships. A pedigree with complete genomes for every individual enables the study of allele frequency dynamics and haplotype diversity across generations, including deviations from neutrality such as transmission distortion. When studying heritable diseases, ancestral haplotypes can be used to augment genome-wide association studies or compute polygenic risk scores for the reconstructed individuals.The building blocks of our reconstruction algorithm are segments of Identity-By-Descent (IBD) shared between two or more genotyped individuals. The method alternates between finding a source for each IBD segment and assembling IBD segments placed within each ancestral individual. After each iteration we perform conflict resolution to remove IBD segments that do not align with wellreconstructed haplotypes and upweight the probability that these segments should be placed in other individuals. We repeat this process until we are no longer successfully reconstructing additional ancestral haplotypes. Unlike previous approaches, our method is able to accommodate complex pedigree structures with hundreds of individuals genotyped at millions of SNPs.We apply our method to an Old Order Amish pedigree from Lancaster, Pennsylvania, whose founders came to the United States from Europe during the early 18th century. The pedigree includes 1338 individuals from the past 10 generations, 394 with genotype data. The motivation for reconstruction is to understand the genetic basis of diseases segregating in the family through tracking haplotype transmission over time. Using our algorithm thread, we are able to reconstruct an average of 230 ancestral individuals per autosome. thread was developed for endogamous populations, but can be applied to any extensive pedigree with the recent generations genotyped. We anticipate that this type of practical ancestral reconstruction will become more common and necessary to understand rare and complex heritable diseases in extended families.

show abstract

IBD-Groupon: an efficient method for detecting group-wise identity-by-descent regions simultaneously in multiple individuals based on pairwise IBD relationships

Cited by 16 publications

References 14 publications

Discovering genes involved in disease and the mystery of missing heritability

Discovering genes involved in disease and the mystery of missing heritability

PIGS: improved estimates of identity-by-descent probabilities by probabilistic IBD graph sampling

Ancestral Haplotype Reconstruction in Endogamous Populations using Identity-By-Descent

Contact Info

Product

Resources

About