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Accurate estimation of cell-type resolution transcriptome in bulk tissue through matrix completion

By Weixu Wang, Jun Yao, Yi Wang, Chao Zhang, Wei Tao, Jiahua Zou, Ting Ni

Posted 01 Jul 2021
bioRxiv DOI: 10.1101/2021.06.30.450493

Single cell RNA-seq (scRNA-seq) has been widely used to uncover cellular heterogeneity, however, the constraints of cost make it impractical as a routine on large patient cohorts. Here we present ENIGMA, a method that accurately deconvolute bulk tissue RNA-seq into single cell-type resolution given the knowledge gained from scRNA-seq. ENIGMA applies a matrix completion strategy to minimize the distance between mixture transcriptome and weighted combination of cell type-specific expression, allowing quantification of cell type proportions and reconstruction of cell type-specific transcriptome. The superior performance of ENIGMA was validated in simulated and realistic datasets, including disease-related tissues, demonstrating its ability in novel biological findings.

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