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Preprints, Working Papers, ... Year : 2023

scBoolSeq: Linking scRNA-Seq Statistics and Boolean Dynamics

Abstract

Boolean networks are largely employed to model the qualitative dynamics of cell fate processes by describing the change of binary activation states of genes and transcription factors with time. Being able to bridge such qualitative states with quantitative measurements of gene expressions in cells, as scRNA-Seq, is a cornerstone for data-driven model construction and validation. On one hand, scRNA-Seq binarisation is a key step for inferring and validating Boolean models. On the other hand, the generation of synthetic scRNA-Seq data from baseline Boolean models provides an important asset to benchmark inference methods. However, linking characteristics of scRNA-Seq datasets, including dropout events, with Boolean states is a challenging task. We present scBoolSeq, a method for the bidirectional linking of scRNA-Seq data and Boolean activation state of genes. Given a reference scRNA-Seq dataset, scBoolSeq computes statistical criteria to classify the empirical gene pseudocount distributions as either unimodal, bimodal, or zero-inflated, and fit a probabilistic model of dropouts, with gene-dependent parameters. From these learnt distributions, scBoolSeq can perform both binarisation of scRNA-Seq datasets, and generate synthetic scRNA-Seq datasets from Boolean trajectories, as issued from Boolean networks, using biased sampling and dropout simulation. We present a case study demonstrating the application of scBoolSeq’s binarisation scheme in data-driven model inference. Furthermore, we compare synthetic scRNA-Seq data generated by scBoolSeq with BoolODE from the same Boolean Network model. The comparison shows that our method better reproduces the statistics of real scRNA-Seq datasets, such as the mean-variance and mean-dropout relationships while exhibiting clearly defined trajectories in a two-dimensional projection of the data.
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Dates and versions

hal-04294917 , version 1 (20-11-2023)

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Gustavo Magaña López, Laurence Calzone, Andrei Zinovyev, Loïc Paulevé. scBoolSeq: Linking scRNA-Seq Statistics and Boolean Dynamics. 2023. ⟨hal-04294917⟩
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