Iterative pruning PCA improves resolution of highly structured populations.
BACKGROUND
Non-random patterns of genetic variation exist among individuals in a population owing to a variety of evolutionary factors. Therefore, populations are structured into genetically distinct subpopulations. As genotypic datasets become ever larger, it is increasingly difficult to correctly estimate the number of subpopulations and assign individuals to them. The computationally efficient non-parametric, chiefly Principal Components Analysis (PCA)-based methods are thus becoming increasingly relied upon for population structure analysis. Current PCA-based methods can accurately detect structure; however, the accuracy in resolving subpopulations and assigning individuals to them is wanting. When subpopulations are closely related to one another, they overlap in PCA space and appear as a conglomerate. This problem is exacerbated when some subpopulations in the dataset are genetically far removed from others. We propose a novel PCA-based framework which addresses this shortcoming.


RESULTS
A novel population structure analysis algorithm called iterative pruning PCA (ipPCA) was developed which assigns individuals to subpopulations and infers the total number of subpopulations present. Genotypic data from simulated and real population datasets with different degrees of structure were analyzed. For datasets with simple structures, the subpopulation assignments of individuals made by ipPCA were largely consistent with the STRUCTURE, BAPS and AWclust algorithms. On the other hand, highly structured populations containing many closely related subpopulations could be accurately resolved only by ipPCA, and not by other methods.


CONCLUSIONS
The algorithm is computationally efficient and not constrained by the dataset complexity. This systematic subpopulation assignment approach removes the need for prior population labels, which could be advantageous when cryptic stratification is encountered in datasets containing individuals otherwise assumed to belong to a homogenous population.
Intarapanich
Apichart
A
BIOTEC 113 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumtani 12120, Thailand. apichart.int@nectec.or.th
Shaw
Philip J
PJ
Assawamakin
Anunchai
A
Wangkumhang
Pongsakorn
P
Ngamphiw
Chumpol
C
Chaichoompu
Kridsadakorn
K
Piriyapongsa
Jittima
J
Tongsima
Sissades
S
D000465:Algorithms; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D014644:Genetic Variation; D005828:Genetics, Population; D006801:Humans; D008957:Models, Genetic; D011153:Population / Q000235:genetics*; D025341:Principal Component Analysis / Q000379:methods*