A method for allocating low-coverage sequencing resources by targeting haplotypes rather than individuals

View/ Open
Issue date
2017-10-25Suggested citation
Ros Freixedes, Roger;
Gonen, Serap;
Gorjanc, Gregor;
Hickey, John M.;
.
(2017)
.
A method for allocating low-coverage sequencing resources by targeting haplotypes rather than individuals.
Genetics Selection Evolution, 2017, vol. 49, article number 78.
https://doi.org/10.1186/s12711-017-0353-y.
Metadata
Show full item recordAbstract
Background: This paper describes a heuristic method for allocating low-coverage sequencing resources by target- ing haplotypes rather than individuals. Low-coverage sequencing assembles high-coverage sequence information for every individual by accumulating data from the genome segments that they share with many other individuals into consensus haplotypes. Deriving the consensus haplotypes accurately is critical for achieving a high phasing and imputation accuracy. In order to enable accurate phasing and imputation of sequence information for the whole population, we allocate the available sequencing resources among individuals with existing phased genomic data by targeting the sequencing coverage of their haplotypes. Results: Our method, called AlphaSeqOpt, prioritizes haplotypes using a score function that is based on the fre- quency of the haplotypes in the sequencing set relative to the target coverage. AlphaSeqOpt has two steps: (1) selec- tion of an initial set of individuals by iteratively choosing the individuals that have the maximum score conditional on the current set, and (2) refinement of the set through several rounds of exchanges of individuals. AlphaSeqOpt is very effective for distributing a fixed amount of sequencing resources evenly across haplotypes, which results in a reduction of the proportion of haplotypes that are sequenced below the target coverage. AlphaSeqOpt can provide a greater proportion of haplotypes sequenced at the target coverage by sequencing less individuals, as compared with other methods that use a score function based on haplotype frequencies in the population. A refinement of the initially selected set can provide a larger more diverse set with more unique individuals, which is beneficial in the context of low-coverage sequencing. We extend the method with an approach for filtering rare haplotypes based on their flanking haplotypes, so that only those that are likely to derive from a recombination event are targeted. Conclusions: We present a method for allocating sequencing resources so that a greater proportion of haplotypes are sequenced at a coverage that is sufficiently high for population-based imputation with low-coverage sequencing. The haplotype score function, the refinement step, and the new approach for filtering rare haplotypes make AlphaSe- qOpt more effective for that purpose than previously reported methods for reducing sequencing redundancy.
Is part of
Genetics Selection Evolution, 2017, vol. 49, article number 78European research projects
Collections
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as cc-by (c) Ros Freixedes, Roger et al., 2017
Related items
Showing items related by title, author, creator and subject.
-
Impact of index hopping and bias towards the reference allele on accuracy of genotype calls from low-coverage sequencing
Ros Freixedes, Roger; Battagin, Mara; Johnsson, Martin; Gorjanc, Gregor; Mileham, Alan J.; Rounsley, Steve D.; Hickey, John M. (BMC (part of Springer Nature), 2018-12-13)Background: Inherent sources of error and bias that affect the quality of sequence data include index hopping and bias towards the reference allele. The impact of these artefacts is likely greater for low-coverage data ... -
Hybrid peeling for fast and accurate calling, phasing, and imputation with sequence data of any coverage in pedigrees
Whalen, Andrew; Ros Freixedes, Roger; Wilson, David L.; Gorjanc, Gregor; Hickey, John M. (BMC (part of Springer Nature), 2018-12-18)Background: In this paper, we extend multi-locus iterative peeling to provide a computationally efficient method for calling, phasing, and imputing sequence data of any coverage in small or large pedigrees. Our method, ... -
A method for the allocation of sequencing resources in genotyped livestock populations
Gonen, Serap; Ros Freixedes, Roger; Battagin, Mara; Gorjanc, Gregor; Hickey, John M. (BMC (part of Springer Nature), 2017-05-18)Background: This paper describes a method, called AlphaSeqOpt, for the allocation of sequencing resources in livestock populations with existing phased genomic data to maximise the ability to phase and impute sequenced ...