Title
MatchMixeR: A Cross-platform Normalization Method for Gene Expression Data Integration.
Abstract
Motivation: Combining gene expression (GE) profiles generated from different platforms enables previously infeasible studies due to sample size limitations. Several cross-platform normalization methods have been developed to remove the systematic differences between platforms, but they may also remove meaningful biological differences among datasets. In this work, we propose a novel approach that removes the platform, not the biological differences. Dubbed as 'MatchMixeR', we model platform differences by a linear mixed effects regression (LMER) model, and estimate them from matched GE profiles of the same cell line or tissue measured on different platforms. The resulting model can then be used to remove platform differences in other datasets. By using LMER, we achieve better bias-variance trade-off in parameter estimation. We also design a computationally efficient algorithm based on the moment method, which is ideal for ultra-high-dimensional LMER analysis. Results: Compared with several prominent competing methods, MatchMixeR achieved the highest after-normalization concordance. Subsequent differential expression analyses based on datasets integrated from different platforms showed that using MatchMixeR achieved the best trade-off between true and false discoveries, and this advantage is more apparent in datasets with limited samples or unbalanced group proportions.
Year
DOI
Venue
2020
10.1093/bioinformatics/btz974
BIOINFORMATICS
DocType
Volume
Issue
Journal
36
8
ISSN
Citations 
PageRank 
1367-4803
0
0.34
References 
Authors
0
5
Name
Order
Citations
PageRank
Serin Zhang100.34
Jiang Shao200.34
Disa Yu320.69
Xing Qiu419312.55
Jinfeng Zhang58610.11