ScMerge Leverages Factor Analysis, Stable Expression, and Pseudoreplication to Merge Multiple Single-cell RNA-seq Datasets

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2019 Apr 28

PMID 31028141

Citations 82

Authors

Yingxin Lin

Shila Ghazanfar

Kevin Y X Wang

Johann A Gagnon-Bartsch

Kitty K Lo

Xianbin Su

Ze-Guang Han

John T Ormerod

Terence P Speed

Pengyi Yang

Jean Yee Hwa Yang

Affiliations

Soon will be listed here.

Abstract

Concerted examination of multiple collections of single-cell RNA sequencing (RNA-seq) data promises further biological insights that cannot be uncovered with individual datasets. Here we present scMerge, an algorithm that integrates multiple single-cell RNA-seq datasets using factor analysis of stably expressed genes and pseudoreplicates across datasets. Using a large collection of public datasets, we benchmark scMerge against published methods and demonstrate that it consistently provides improved cell type separation by removing unwanted factors; scMerge can also enhance biological discovery through robust data integration, which we show through the inference of development trajectory in a liver dataset collection.

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References

Eisenberg E, Levanon E . Human housekeeping genes are compact. Trends Genet. 2003; 19(7):362-5. DOI: 10.1016/S0168-9525(03)00140-9. View

Hanchate N, Kondoh K, Lu Z, Kuang D, Ye X, Qiu X . Single-cell transcriptomics reveals receptor transformations during olfactory neurogenesis. Science. 2015; 350(6265):1251-5. PMC: 5642900. DOI: 10.1126/science.aad2456. View

Johnson W, Li C, Rabinovic A . Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2006; 8(1):118-27. DOI: 10.1093/biostatistics/kxj037. View

Clauset A, Newman M, Moore C . Finding community structure in very large networks. Phys Rev E Stat Nonlin Soft Matter Phys. 2005; 70(6 Pt 2):066111. DOI: 10.1103/PhysRevE.70.066111. View

Bacher R, Chu L, Leng N, Gasch A, Thomson J, Stewart R . SCnorm: robust normalization of single-cell RNA-seq data. Nat Methods. 2017; 14(6):584-586. PMC: 5473255. DOI: 10.1038/nmeth.4263. View

Eisenberg E, Levanon E . Human housekeeping genes, revisited. Trends Genet. 2013; 29(10):569-74. DOI: 10.1016/j.tig.2013.05.010. View

Musch A . From a common progenitor to distinct liver epithelial phenotypes. Curr Opin Cell Biol. 2018; 54:18-23. PMC: 6119654. DOI: 10.1016/j.ceb.2018.02.008. View

Suter D, Molina N, Gatfield D, Schneider K, Schibler U, Naef F . Mammalian genes are transcribed with widely different bursting kinetics. Science. 2011; 332(6028):472-4. DOI: 10.1126/science.1198817. View

Gagnon-Bartsch J, Speed T . Using control genes to correct for unwanted variation in microarray data. Biostatistics. 2011; 13(3):539-52. PMC: 3577104. DOI: 10.1093/biostatistics/kxr034. View

10.

Ghazanfar S, Bisogni A, Ormerod J, Lin D, Yang J . Integrated single cell data analysis reveals cell specific networks and novel coactivation markers. BMC Syst Biol. 2017; 10(Suppl 5):127. PMC: 5249008. DOI: 10.1186/s12918-016-0370-4. View

11.

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

12.

Yan L, Yang M, Guo H, Yang L, Wu J, Li R . Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells. Nat Struct Mol Biol. 2013; 20(9):1131-9. DOI: 10.1038/nsmb.2660. View

13.

Lawlor N, George J, Bolisetty M, Kursawe R, Sun L, Sivakamasundari V . Single-cell transcriptomes identify human islet cell signatures and reveal cell-type-specific expression changes in type 2 diabetes. Genome Res. 2016; 27(2):208-222. PMC: 5287227. DOI: 10.1101/gr.212720.116. View

14.

Fan X, Zhang X, Wu X, Guo H, Hu Y, Tang F . Single-cell RNA-seq transcriptome analysis of linear and circular RNAs in mouse preimplantation embryos. Genome Biol. 2015; 16:148. PMC: 4511241. DOI: 10.1186/s13059-015-0706-1. View

15.

Baron M, Veres A, Wolock S, Faust A, Gaujoux R, Vetere A . A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure. Cell Syst. 2016; 3(4):346-360.e4. PMC: 5228327. DOI: 10.1016/j.cels.2016.08.011. View

16.

Xin Y, Kim J, Okamoto H, Ni M, Wei Y, Adler C . RNA Sequencing of Single Human Islet Cells Reveals Type 2 Diabetes Genes. Cell Metab. 2016; 24(4):608-615. DOI: 10.1016/j.cmet.2016.08.018. View

17.

Xue Z, Huang K, Cai C, Cai L, Jiang C, Feng Y . Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing. Nature. 2013; 500(7464):593-7. PMC: 4950944. DOI: 10.1038/nature12364. View

18.

Goolam M, Scialdone A, Graham S, Macaulay I, Jedrusik A, Hupalowska A . Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos. Cell. 2016; 165(1):61-74. PMC: 4819611. DOI: 10.1016/j.cell.2016.01.047. View

19.

Camp J, Sekine K, Gerber T, Loeffler-Wirth H, Binder H, Gac M . Multilineage communication regulates human liver bud development from pluripotency. Nature. 2017; 546(7659):533-538. DOI: 10.1038/nature22796. View

20.

Blakeley P, Fogarty N, Del Valle I, Wamaitha S, Hu T, Elder K . Defining the three cell lineages of the human blastocyst by single-cell RNA-seq. Development. 2015; 142(20):3613. PMC: 4631772. DOI: 10.1242/dev.131235. View