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快乐十分选三机选:scMerge leverages factor analysis, stable expression, and pseudoreplication to merge multiple single-cell RNA-seq datasets
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Single-cell RNA-sequencing (scRNA-seq) profiling has exploded in recent years and enabled new biological knowledge to be discovered at the single-cell level. Successful and flexible integration of scRNA-Seq datasets from multiple sources promises to be an effective avenue to obtain further biological insights. This study presents a comprehensive approach to integration for scRNA-seq data analysis. It addresses the challenges involved in successful integration of scRNA-seq datasets by using the knowledge of genes that appear not to change across all samples and a robust algorithm to infer pseudoreplicates between datasets. This information is then consolidated into a single-factor model that enables tailored incorporation of prior knowledge. The effectiveness of scMerge is demonstrated by extensive comparison with other approaches.
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.
?1S.G. and K.Y.X.W. contributed equally to this work.
- ?2To whom correspondence may be addressed. Email: or .
Author contributions: S.G., K.Y.X.W., P.Y., and J.Y.H.Y. designed research; Y.L., S.G., K.Y.X.W., J.A.G.-B., J.T.O., T.P.S., P.Y., and J.Y.H.Y. performed research; Y.L., K.Y.X.W., J.A.G.-B., and J.T.O. contributed new reagents/analytic tools; Y.L., S.G., K.Y.X.W., J.A.G.-B., X.S., Z.-G.H., T.P.S., P.Y., and J.Y.H.Y. analyzed data; Y.L., S.G., K.Y.X.W., K.K.L., T.P.S., P.Y., and J.Y.H.Y. wrote the paper; and Y.L., K.K.L., and J.Y.H.Y. processed and curated all data.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The R package scMerge is available on the Github repository (https://sydneybiox.github.io/scMerge).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1820006116/-/DCSupplemental.
Published under the PNAS license.