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

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cam.issuedOnline2022-03-25
dc.contributor.authorZhang, Mengqi
dc.contributor.authorGuo, F Richard
dc.contributor.orcidZhang, Mengqi [0000-0002-1091-1014]
dc.contributor.orcidGuo, F Richard [0000-0002-2081-7398]
dc.date.accessioned2022-06-14T01:02:52Z
dc.date.available2022-06-14T01:02:52Z
dc.date.issued2022-03-25
dc.date.updated2022-06-14T01:02:52Z
dc.description.abstractMOTIVATION: 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 doi.org/10.5281/zenodo.6332254. For real data analysis with the R package, see doi.org/10.5281/zenodo.6332566. These can also be accessed thorough GitHub at github.com/mqzhanglab/BSDE and github.com/mqzhanglab/BSDE_pipeline. The two single cell sequencing datasets can be download with UCSC cell browser from cells.ucsc.edu/?ds=ms and cells.ucsc.edu/?ds=lung-pf-control. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
dc.identifier.citationBioinformatics (Oxford, England), volume 38, issue 10, page 2765-2772
dc.identifier.doi10.17863/CAM.85462
dc.identifier.eissn1367-4811
dc.identifier.issn1367-4803
dc.identifier.other35561165
dc.identifier.otherPMC9113363
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338053
dc.languageeng
dc.language.isoeng
dc.publisherOxford University Press (OUP)
dc.publisher.urlhttp://dx.doi.org/10.1093/bioinformatics/btac171
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 9808944
dc.sourceessn: 1367-4811
dc.subject31 Biological Sciences
dc.subject3102 Bioinformatics and Computational Biology
dc.subject3105 Genetics
dc.subjectLung
dc.subjectGeneric health relevance
dc.subjectCase-Control Studies
dc.subjectHumans
dc.subjectSoftware
dc.titleBSDE: Barycenter Single-Cell Differential Expression for Case-Control Studies.
dc.typeArticle
dcterms.dateAccepted2022-03-23
prism.publicationNameBioinformatics
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1093/bioinformatics/btac171

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