SC-JNMF: Single-cell clustering integrating multiple quantification methods based on joint non-negative matrix factorization

A bstract Unsupervised cell clustering is important in discovering cell diversity and subpopulations. Single-cell clustering using gene expression profiles is known to show different results depending on the method of expression quantification; nevertheless, most single-cell clustering methods do not consider the method. In this article, we propose a robust and highly accurate clustering method using joint non-negative matrix factorization (joint NMF) based on multiple gene expression profiles quantified using different methods. Matrix factorization is an excellent method for dimension reduction and feature extraction of data. In particular, NMF approximates the data matrix as the product of two matrices in which all factors are non-negative. Our joint NMF can extract common factors among multiple gene expression profiles by applying each NMF to them under the constraint that one of the factorized matrices is shared among the multiple NMFs. The joint NMF determines more robust and accurate cell clustering results by leveraging multiple quantification methods compared to the conventional clustering methods, which uses only a single quantification method. In conclusion, our study showed that our clustering method using multiple gene expression profiles is more accurate than other popular methods.