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.

(1) Ker (f,) is a characteristic subgroup of T,(M),(2) the group G leaves Ker (f*) invariant. This assumption is needed in the last two statements of Corollary 6,(vi) of Theorems 8, Theorem 11 and Theorem 13. In Theorem 12, the corresponding assumption can be stated as follows: Let H be the subspace of H,(M, I?) defined by {PIP U ai, U... U ai, _,= 0 for all ii}. Then G leaves H invariant.

The discrete fracture model (DFM) has been widely used in the simulation of fluid flow in fractured porous media. Traditional DFM uses the so-called hybrid-dimensional approach to treat fractures explicitly as low-dimensional entries (e.g. line entries in 2D media and face entries in 3D media) on the interfaces of matrix cells and then couple the matrix and fracture flow systems together based on the principle of superposition with the fracture thickness used as the dimensional homogeneity factor. Because of this methodology, DFM is considered to be limited on conforming meshes and thus may raise difficulties in generating high quality unstructured meshes due to the complexity of fracture's geometrical morphology. In this paper, we clarify that the DFM actually can be extended to non-conforming meshes without any essential changes. To show it clearly, we provide another perspective for DFM based on hybrid-dimensional representation of permeability tensor to describe fractures as one-dimensional line Dirac delta functions contained in permeability tensor. A finite element DFM scheme for single-phase flow on non-conforming meshes is then derived by applying Galerkin finite element method to it. Analytical analysis and numerical experiments show that our DFM automatically degenerates to the classical finite element DFM when the mesh is conforming with fractures. Moreover, the accuracy and efficiency of the model on non-conforming meshes are demonstrated by testing several benchmark problems. This model is also applicable to curved fracture with variable thickness.

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