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c-CSN:Single-cell RNA Sequencing Data Analysis by Conditional Cell-specific Network

Genomics, Proteomics & Bioinformatics 2021年第2期19卷 319-329页

作者： Lin Li Hao Dai Zhaoyuan Fang Luonan Chen Key Laboratory of Systems Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China Shanghai Research Center for Brain Science and Brain-Inspired Intelligence Shanghai 201210China CAS Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China Hangzhou Institute for Advanced Study Chinese Academy of SciencesHangzhou 310024China

t The rapid advancement of single-cell technologies has shed new light on the complex mechanisms of cellular ***,compared to bulk RNA sequencing(RNA-seq),single-cell RNA-seq(scRNA-seq)suffers from higher noise and lower coverage,which brings new computational *** on statistical independence,cell-specific network(CSN)is able to quantify the overall associations between genes for each cell,yet suffering from a problem of overestimation related to indirect *** overcome this problem,we propose the c-CSN method,which can construct the conditional cell-specific network(CCSN)for each cell.c-CSN method can measure the direct associations between genes by eliminating the indirect associations.c-CSN can be used for cell clustering and dimension reduction on a network basis of single ***,each CCSN can be viewed as the transformation from less“reliable”gene expression to more“reliable”gene–gene associations in a *** on CCSN,we further design network flow entropy(NFE)to estimate the differentiation potency of a single cell.A number of scRNA-seq datasets were used to demonstrate the advantages of our approach.1)One direct association network is generated for one cell.2)Most existing scRNA-seq methods designed for gene expression matrices are also applicable to c-CSN-transformed degree matrices.3)CCSN-based NFE helps resolving the direction of differentiation trajectories by quantifying the potency of each cell.c-CSN is publicly available at https://***/LinLi-0909/c-CSN.

关键词： Network flow entropy Cell-specific network Single-cell network direct association Conditional independence

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