Apr 13, 2020

A Bayesian framework for inter-cellular information sharing improves dscRNA-seq quantification

BioRxiv : the Preprint Server for Biology
Avi SrivastavaRob Patro

Abstract

Motivation: Droplet based single cell RNA-seq (dscRNA-seq) data is being generated at an unprecedented pace, and the accurate estimation of gene level abundances for each cell is a crucial first step in most dscRNA-seq analyses. When preprocessing the raw dscRNA-seq data to generate a count matrix, care must be taken to account for the potentially large number of multi-mapping locations per read. The sparsity of dscRNA-seq data, and the strong 3-prime sampling bias, makes it difficult to disambiguate cases where there is no uniquely mapping read to any of the candidate target genes. Results: We introduce a Bayesian framework for information sharing across cells within a sample, or across multiple modalities of data using the same sample, to improve gene quantification estimates for dscRNA-seq data. We use an anchor-based approach to connect cells with similar gene expression patterns, and learn informative, empirical priors which we provide to alevins gene multi-mapping resolution algorithm. This improves the quantification estimates for genes with no uniquely mapping reads (i.e. when there is no unique intra-cellular information). We show our new model improves the per cell gene level estimates and provides a principled framew...Continue Reading

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