KLFDAPC: a supervised machine learning approach for spatial genetic structure analysis.

KLFDAPC: a supervised machine learning approach for spatial genetic structure analysis.
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DOI:
10.1093/bib/bbac202
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发表时间:
2022-07-18
影响因子:
9.5
通讯作者:
--
中科院分区:
生物学2区
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--
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人类遗传变异的地理模式为人类进化和疾病提供了重要的见解。检测和描述它们的常用工具是主成分分析(PCA)或主成分的监督线性判别分析(DAPC)。然而,从这两种方法产生的遗传特征可能无法正确地描述复杂的情况下,涉及混合物的人口结构。在这项研究中,我们引入核局部Fisher判别分析的主成分(KLFDAPC),一个监督的非线性方法推断个人的地理遗传结构,可以纠正这些方法的局限性,通过保留多模态空间的样本。我们测试了KLFDAPC推断种群结构和使用神经网络预测个体地理来源的能力。仿真结果表明,KLFDAPC比PCA和DAPC具有更高的区分能力。将我们的方法应用于欧洲和东亚的全基因组遗传数据集表明,与PCA和DAPC相比,KLFDAPC的前两个简化特征正确地概括了个体的地理位置,并显着提高了预测个体地理起源的准确性。因此,KLFDAPC可用于地理祖先推断、基因组扫描设计和校正GWAS中将基因与适应或疾病易感性联系起来的空间分层。
Geographic patterns of human genetic variation provide important insights into human evolution and disease. A commonly used tool to detect and describe them is principal component analysis (PCA) or the supervised linear discriminant analysis of principal components (DAPC). However, genetic features produced from both approaches could fail to correctly characterize population structure for complex scenarios involving admixture. In this study, we introduce Kernel Local Fisher Discriminant Analysis of Principal Components (KLFDAPC), a supervised non-linear approach for inferring individual geographic genetic structure that could rectify the limitations of these approaches by preserving the multimodal space of samples. We tested the power of KLFDAPC to infer population structure and to predict individual geographic origin using neural networks. Simulation results showed that KLFDAPC has higher discriminatory power than PCA and DAPC. The application of our method to empirical European and East Asian genome-wide genetic datasets indicated that the first two reduced features of KLFDAPC correctly recapitulated the geography of individuals and significantly improved the accuracy of predicting individual geographic origin when compared to PCA and DAPC. Therefore, KLFDAPC can be useful for geographic ancestry inference, design of genome scans and correction for spatial stratification in GWAS that link genes to adaptation or disease susceptibility.
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