학술논문

Reconstructing gene regulatory networks of biological function using differential equations of multilayer perceptrons
Document Type
article
Source
BMC Bioinformatics, Vol 23, Iss 1, Pp 1-17 (2022)
Subject
Fully connected neural network
Biological function
Differential equations
Dynamical systems
Link knockout
Computer applications to medicine. Medical informatics
R858-859.7
Biology (General)
QH301-705.5
Language
English
ISSN
1471-2105
Abstract
Abstract Background Building biological networks with a certain function is a challenge in systems biology. For the functionality of small (less than ten nodes) biological networks, most methods are implemented by exhausting all possible network topological spaces. This exhaustive approach is difficult to scale to large-scale biological networks. And regulatory relationships are complex and often nonlinear or non-monotonic, which makes inference using linear models challenging. Results In this paper, we propose a multi-layer perceptron-based differential equation method, which operates by training a fully connected neural network (NN) to simulate the transcription rate of genes in traditional differential equations. We verify whether the regulatory network constructed by the NN method can continue to achieve the expected biological function by verifying the degree of overlap between the regulatory network discovered by NN and the regulatory network constructed by the Hill function. And we validate our approach by adapting to noise signals, regulator knockout, and constructing large-scale gene regulatory networks using link-knockout techniques. We apply a real dataset (the mesoderm inducer Xenopus Brachyury expression) to construct the core topology of the gene regulatory network and find that Xbra is only strongly expressed at moderate levels of activin signaling. Conclusion We have demonstrated from the results that this method has the ability to identify the underlying network topology and functional mechanisms, and can also be applied to larger and more complex gene network topologies.