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1.
Interdiscip Sci ; 2024 Feb 11.
Article in English | MEDLINE | ID: mdl-38342857

ABSTRACT

Since gene regulation is a complex process in which multiple genes act simultaneously, accurately inferring gene regulatory networks (GRNs) is a long-standing challenge in systems biology. Although graph neural networks can formally describe intricate gene expression mechanisms, current GRN inference methods based on graph learning regard only transcription factor (TF)-target gene interactions as pairwise relationships, and cannot model the many-to-many high-order regulatory patterns that prevail among genes. Moreover, these methods often rely on limited prior regulatory knowledge, ignoring the structural information of GRNs in gene expression profiles. Therefore, we propose a multi-view hierarchical hypergraphs GRN (MHHGRN) inference model. Specifically, multiple heterogeneous biological information is integrated to construct multi-view hierarchical hypergraphs of TFs and target genes, using hypergraph convolution networks to model higher order complex regulatory relationships. Meanwhile, the coupled information diffusion mechanism and the cross-domain messaging mechanism facilitate the information sharing between genes to optimise gene embedding representations. Finally, a unique channel attention mechanism is used to adaptively learn feature representations from multiple views for GRN inference. Experimental results show that MHHGRN achieves better results than the baseline methods on the E. coli and S. cerevisiae benchmark datasets of the DREAM5 challenge, and it has excellent cross-species generalization, achieving comparable or better performance on scRNA-seq datasets from five mouse and two human cell lines.

2.
IEEE J Transl Eng Health Med ; 8: 1400310, 2020.
Article in English | MEDLINE | ID: mdl-32419989

ABSTRACT

Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases, and the number of AD patients has increased year after year with the global aging trend. The onset of AD has a long preclinical stage. If doctors can make an initial diagnosis in the mild cognitive impairment (MCI) stage, it is possible to identify and screen those at a high-risk of developing full-blown AD, and thus the number of new AD patients can be reduced. However, there are problems with the medical datasets including AD data, such as insufficient number of samples and different data distributions. Transfer learning, which can effectively solve the problem of distribution discrepancy between training and test data and an insufficient number of target samples, has attracted increasing attention over recent years. In this paper, we propose a multi-source ensemble transfer learning (METL) approach by introducing ensemble learning and our tri-transfer model that uses Tri-Training, which ensures the transferability of source data by the tri-transfer model and high performance through ensemble learning. The experimental results on the benchmark and AD datasets demonstrate that our proposed approach has effective transferability, robustness, and feasibility, and is superior to existing algorithms. Based on METL, we propose an auxiliary diagnosis system for the initial diagnosis of AD, which helps doctors identify patients in the MCI stage as quickly as possible and with high accuracy so that measures can be taken to prevent or delay the occurrence of AD.

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