MathSciDoc: An Archive for Mathematician ∫

Quantitatively identifying direct dependencies between variables is an important task in data analysis, in particular for reconstructing various types of networks and causal relations in science and engineering. One of the most widely used criteria is partial correlation, but it can only measure linearly direct association and miss nonlinear associations. However, based on conditional independence, conditional mutual information (CMI) is able to quantify nonlinearly direct relationships among variables from the observed data, superior to linear measures, but suffers from a serious problem of underestimation, in particular for those variables with tight associations in a network, which severely limits its applications. In this work, we propose a new concept, “partial independence,” with a new measure, “part mutual information” (PMI), which not only can overcome the problem of CMI but also retains the quantification properties of both mutual information (MI) and CMI. Specifically, we first defined PMI to measure nonlinearly direct dependencies between variables and then derived its relations with MI and CMI. Finally, we used a number of simulated data as benchmark examples to numerically demonstrate PMI features and further real gene expression data from Escherichia coli and yeast to reconstruct gene regulatory networks, which all validated the advantages of PMI for accurately quantifying nonlinearly direct associations in networks.

Modeling cell differentiation from omics data is an essential problem in systems biology research. Although many algorithms have been established to analyze scRNA-seq data, approaches to infer the pseudo-time of cells or quantify their potency have not yet been satisfactorily solved. Here, we propose the Landscape of Differentiation Dynamics (LDD) method, which calculates cell potentials and constructs their differentiation landscape by a continuous birth-death process from scRNA-seq data. From the viewpoint of stochastic dynamics, we exploited the features of the differentiation process and quantified the differentiation landscape based on the source-sink diffusion process. In comparison with other scRNA-seq methods in seven benchmark datasets, we found that LDD could accurately and efficiently build the evolution tree of cells with pseudo-time, in particular quantifying their differentiation landscape in terms of potency. This study provides not only a computational tool to quantify cell potency or the Waddington potential landscape based on scRNA-seq data, but also novel insights to understand the cell differentiation process from a dynamic perspective.