Complete deconvolution analysis for bulk RNA-seq data is important and helpful to distinguish whether the differences of disease-associated GEPs (gene expression profiles) in tissues of patients and normal controls are due to changes in cellular composition of tissue samples, or due to GEPs changes in specific cells. One of the major techniques to perform complete deconvolution is nonnegative matrix factorization (NMF), which also has a wide-range of applications in the machine learning community. However, the NMF is a well-known strongly ill-posed problem, so a direct application of NMF to RNA-seq data will suffer severe difficulties in the interpretability of solutions. In this paper, we develop an NMF-based mathematical model and corresponding computational algorithms to improve the solution identifiability of deconvoluting bulk RNA-seq data. In our approach, we combine the biological concept of marker genes with the solvability conditions of the NMF theories, and develop a geometric structures guided optimization model. In this strategy, the geometric structure of bulk tissue data is first explored by the spectral clustering technique. Then, the identified information of marker genes is integrated as solvability constraints, while the overall correlation graph is used as manifold regularization. Both synthetic and biological data are used to validate the proposed model and algorithms, from which solution interpretability and accuracy are significantly improved.
We establish a new theory which unifies various aspects of topological approaches for data science, by being applicable both to point cloud data and to graph data, including networks beyond pairwise interactions. We generalize simplicial complexes and hypergraphs to super-hypergraphs and establish super-hypergraph homology as an extension of simplicial homology. Driven by applications, we also introduce super-persistent homology.
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