Title
A data denoising approach to optimize functional clustering of single cell RNA-sequencing data
Abstract
Single cell RNA-sequencing (scRNA-seq) technology enables comprehensive transcriptomic profiling of thousands of cells with distinct phenotypic and physiological states in a complex tissue. Substantial efforts have been made to characterize single cells of distinct identities from scRNA-seq data, including various cell clustering techniques. While existing approaches can handle single cells in terms of different cell (sub)types at a high resolution, identification of the functional variability within the same cell type remains unsolved. In addition, there is a lack of robust method to handle the inter-subject variation that often brings severe confounding effects for the functional clustering of single cells. In this study, we developed a novel data denoising and cell clustering approach, namely CIBS, to provide biologically explainable functional classification for scRNA-seq data. CIBS is based on a systems biology model of transcriptional regulation that assumes a multi-modality distribution of the cells' activation status, and it utilizes a Boolean matrix factorization approach on the discretized expression status to robustly derive functional modules. CIBS is empowered by a novel fast Boolean Matrix Factorization method, namely PFAST, to increase the computational feasibility on large scale scRNA-seq data. Application of CIBS on two scRNA-seq datasets collected from cancer tumor micro-environment successfully identified subgroups of cancer cells with distinct expression patterns of epithelial-mesenchymal transition and extracellular matrix marker genes, which was not revealed by the existing cell clustering analysis tools. The identified cell groups were significantly associated with the clinically confirmed lymph-node invasion and metastasis events across different patients.
Year
DOI
Venue
2020
10.1109/BIBM49941.2020.9313483
2020 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)
Keywords
DocType
ISBN
Cell clustering analysis,Data denoising,Boolean matrix factorization,Cancer microenvirionment,Metastasis
Conference
978-1-7281-6216-4
Citations 
PageRank 
References 
0
0.34
0
Authors
7
Name
Order
Citations
PageRank
Changlin Wan133.79
Dongya Jia221.08
Yue Zhao318633.54
Wennan Chang4134.10
Sha Cao534.85
Xiao Wang654.61
Zhang Chi7107.64