Weighted deep factorizing heterogeneous molecular network for genome-phenome association prediction.

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Abstract

Genome-phenome association (GPA) prediction can promote the understanding of biological mechanisms about complex pathology of phenotypes (i.e., traits and diseases). Traditional heterogeneous network-based GPA approaches overwhelmingly need to project heterogeneous data toward homogeneous network for data fusion and prediction, such projections result in the loss of heterogeneous network structure information. Matrix factorization based data fusion can avoid such projection by integrating multi-type data in a coherent way, but they typically perform linear factorization and cannot mine the nonlinear relationships between molecules, which compromise the accuracy of GPA analysis. Furthermore, most of them can not selectively synergy network topology and node attribution information in a principle way. In this paper, we propose a weighted deep matrix factorization based solution (WDGPA) to predict GPAs by selectively and differentially fusing heterogeneous molecular network and diverse attributes of nodes. WDGPA firstly assigns weights to inter/intra-relational data matrices and attribute data matrices, and performs deep matrix factorization on these matrices of heterogeneous network in a cooperative manner to obtain the nonlinear representations of different nodes. In addition, it performs low-rank representation learning on the attribute data with the shared nonlinear representations. In this way, both the network topology and node attributes are jointly mined to explore the representations of molecules and complex interplays between molecules and phenotypes. WDGPA then uses the representational vectors of gene and phenotype nodes to predict GPAs. Experimental results on maize and human datasets confirm that WDGPA outperforms competitive methods by a large margin under different evaluation protocols.Copyright © 2022 Elsevier Inc. All rights reserved.