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BSDE: Barycenter Single-Cell Differential Expression for Case-Control Studies.

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MOTIVATION: Single-cell sequencing brings about a revolutionarily high resolution for finding differentially expressed genes by disentangling highly heterogeneous cell tissues. Yet, such analysis is so far mostly focused on comparing between different cell types from the same individual. As single-cell sequencing becomes cheaper and easier to use, an increasing number of datasets from case-control studies are becoming available, which call for new methods for identifying differential expressions between case and control individuals. RESULTS: To bridge this gap, we propose Barycenter Single-cell Differential Expression (BSDE), a nonparametric method for finding differentially expressed genes for case-control studies. Through the use of optimal transportation for aggregating distributions and computing their distances, our method overcomes the restrictive parametric assumptions imposed by standard mixed-effect-modeling approaches. Through simulations, we show that BSDE can accurately detect a variety of differential expressions while maintaining the type-I error at a prescribed level. Further, 1345 and 1568 cell type specific differentially expressed genes are identified by BSDE from datasets on pulmonary fibrosis and multiple sclerosis, among which the top findings are supported by previous results from the literature. AVAILABILITY: R package BSDE is freely available from For real data analysis with the R package, see These can also be accessed thorough GitHub at and The two single cell sequencing datasets can be download with UCSC cell browser from and SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.



31 Biological Sciences, 3102 Bioinformatics and Computational Biology, 3105 Genetics, Lung, Generic health relevance, Case-Control Studies, Humans, Software

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Oxford University Press (OUP)