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AC-PCA: simultaneous dimension reduction and adjustment for confounding variation

By Zhixiang Lin, Can Yang, Ying Zhu, John C. Duchi, Yao Fu, Yong Wang, Bai Jiang, Mahdi Zamanighomi, Xuming Xu, Mingfeng Li, Nenad Sestan, Hongyu Zhao, Wing Hung Wong

Posted 22 Feb 2016
bioRxiv DOI: 10.1101/040485 (published DOI: 10.1073/pnas.1617317113)

Dimension reduction methods are commonly applied to high-throughput biological datasets. However, the results can be hindered by confounding factors, either biologically or technically originated. In this study, we extend Principal Component Analysis to propose AC-PCA for simultaneous dimension reduction and adjustment for confounding variation. We show that AC-PCA can adjust for a) variations across individual donors present in a human brain exon array dataset, and b) variations of different species in a model organism ENCODE RNA-Seq dataset. Our approach is able to recover the anatomical structure of neocortical regions, and to capture the shared variation among species during embryonic development. For gene selection purposes, we extend AC-PCA with sparsity constraints, and propose and implement an efficient algorithm. The methods developed in this paper can also be applied to more general settings.

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