Towards fine-scale population stratification modeling based on kernel principal component analysis and random forest

Genes Genomics. 2021 Oct;43(10):1143-1155. doi: 10.1007/s13258-021-01057-4. Epub 2021 Jun 7.


Background: Population stratification modeling is essential in Genome-Wide Association Studies.

Objective: In this paper, we aim to build a fine-scale population stratification model to efficiently infer individual genetic ancestry.

Methods: Kernel Principal Component Analysis (PCA) and random forest are adopted to build the population stratification model, together with parameter optimization. We explore different PCA methods, including standard PCA and kernel PCA to extract relevant features from the genotype data that is transformed by vcf2geno, a pipeline from LASER software. These extracted features are fed into a random forest for ensemble learning. Parameter tuning is performed to jointly find the optimal number of principal components, kernel function for PCA and parameters of the random forest.

Results: Experiments based on HGDP dataset show that kernel PCA with Sigmoid function and Gaussian function can achieve higher prediction accuracy than the standard PCA. Compared to standard PCA with the two principal components, the accuracy by using KPCA-Sigmoid with the optimal number of principal components can achieve around 100% and 200% improvement for East Asian and European populations, respectively.

Conclusion: With the optimal parameter configuration on both PCA and random forest, our proposed method can infer the individual genetic ancestry more accurately, given their variants.

Keywords: Association study; Kernel principal component analysis; Population stratification; Random forest.