A method for the allocation of sequencing resources in genotyped livestock populations

Abstract

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 haplotypes into the whole population. Methods: We present two algorithms. The rst selects focal individuals that collectively represent the maximum pos‐ sible portion of the haplotype diversity in the population. The second allocates a xed sequencing budget among the families of focal individuals to enable phasing of their haplotypes at the sequence level. We tested the performance of the two algorithms in simulated pedigrees. For each pedigree, we evaluated the proportion of population haplo‐ types that are carried by the focal individuals and compared our results to a variant of the widely‐used key ancestors approach and to two haplotype‐based approaches. We calculated the expected phasing accuracy of the haplotypes of a focal individual at the sequence level given the proportion of the xed sequencing budget allocated to its family. Results: AlphaSeqOpt maximises the ability to capture and phase the most frequent haplotypes in a population in three ways. First, it selects focal individuals that collectively represent a larger portion of the population haplotype diversity than existing methods. Second, it selects focal individuals from across the pedigree whose haplotypes can be easily phased using family‐based phasing and imputation algorithms, thus maximises the ability to impute sequence into the rest of the population. Third, it allocates more of the xed sequencing budget to focal individuals whose haplotypes are more frequent in the population than to focal individuals whose haplotypes are less frequent. Unlike existing methods, we additionally present an algorithm to allocate part of the sequencing budget to the families (i.e. immediate ancestors) of focal individuals to ensure that their haplotypes can be phased at the sequence level, which is essential for enabling and maximising subsequent sequence imputation. Conclusions: We present a new method for the allocation of a xed sequencing budget to focal individuals and their families such that the nal sequenced haplotypes, when phased at the sequence level, represent the maximum pos‐ sible portion of the haplotype diversity in the population that can be sequenced and phased at that budget.

The authors acknowledge the financial support from the BBSRC ISPG to The Roslin Institute ‘BB/J004235/1’, from Genus PLC and from grant numbers ‘BB/M009254/1’, ‘BB/L020726/1’, ‘BB/N004736/1’, ‘BB/N004728/1’, ‘BB/L020467/1’, BB/N006178/1 and Medical Research Council (MRC) grant number ‘MR/M000370/1’. This work has made use of the resources provided by the Edinburgh Compute and Data Facility (ECDF) (http://www.ecdf.ed.ac.uk).