SCODE – An efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation

The analysis of RNA-Seq data from individual differentiating cells enables us to reconstruct the differentiation process and the degree of differentiation (in pseudo-time) of each cell. Such analyses can reveal detailed expression dynamics and functional relationships for differentiation. To further elucidate differentiation processes, more insight into gene regulatory networks is required. The pseudo-time can be regarded as time information and, therefore, single-cell RNA-Seq data are time-course data with high time resolution. Although time-course data are useful for inferring networks, conventional inference algorithms for such data suffer from high time complexity when the number of samples and genes is large. Therefore, a novel algorithm is necessary to infer networks from single-cell RNA-Seq during differentiation.

In this study, researchers at RIKEN have developed the novel and efficient algorithm SCODE to infer regulatory networks, based on ordinary differential equations. The researchers applied SCODE to three single-cell RNA-Seq datasets and confirmed that SCODE can reconstruct observed expression dynamics. They evaluated SCODE by comparing its inferred networks with use of a DNaseI-footprint based network. The performance of SCODE was best for two of the datasets and nearly best for the remaining dataset. They also compared the runtimes and showed that the runtimes for SCODE are significantly shorter than for alternatives. Thus, this algorithm provides a promising approach for further single-cell differentiation analyses.

Abstract illustration of SCODErna-seq

(a) Sample Z(e) from the ODE of z (b) Estimate W based on linear regression. (c) Optimize B iteratively. (d) Infer A from optimized W and B. (e) The expression dynamics can be reconstructed from the optimized ODE of x.

Availability – The R source code of SCODE is available at

Matsumoto H, Kiryu H, Furusawa C, Ko MSH, Ko SBH, Gouda N, Hayashi T, Nikaido I. (2016) SCODE: An efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation. bioRXiv [Epub ahead of print]. [abstract]

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