PMINR: Pointwise Mutual Information-Based Network Regression – With Application to Studies of Lung Cancer and Alzheimer’s Disease
Authors
Lin, Weiqiang
Ji, Jiadong
Zhu, Yuchen
Li, Mingzhuo
Zhao, Jinghua
Xue, Fuzhong
Yuan, Zhongshang
Publication Date
2020-10-15Journal Title
Frontiers in Genetics
Publisher
Frontiers Media S.A.
Volume
11
Language
en
Type
Article
This Version
VoR
Metadata
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Lin, W., Ji, J., Zhu, Y., Li, M., Zhao, J., Xue, F., & Yuan, Z. (2020). PMINR: Pointwise Mutual Information-Based Network Regression – With Application to Studies of Lung Cancer and Alzheimer’s Disease. Frontiers in Genetics, 11 https://doi.org/10.3389/fgene.2020.556259
Abstract
Complex diseases are believed to be the consequence of intracellular network(s) involving a range of factors. An improved understanding of a disease-predisposing biological network could lead to better identification of genes and pathways that confer disease risk and therefore inform drug development. The group difference in biological networks, as is often characterized by graphs of nodes and edges, is attributable to effects of these nodes and edges. Here we introduced pointwise mutual information (PMI) as a measure of the connection between a pair of nodes with either a linear relationship or nonlinear dependence. We then proposed a PMI-based network regression (PMINR) model to differentiate patterns of network changes (in node or edge) linking a disease outcome. Through simulation studies with various sample sizes and inter-node correlation structures, we showed that PMINR can accurately identify these changes with higher power than current methods and be robust to the network topology. Finally, we illustrated, with publicly available data on lung cancer and gene methylation data on aging and Alzheimer’s disease, an evaluation of the practical performance of PMINR. We concluded that PMI is able to capture the generic inter-node correlation pattern in biological networks, and PMINR is a powerful and efficient approach for biological network analysis.
Keywords
Genetics, biological networks, pointwise mutual information, regression, lung cancer, Alzheimer’s disease
Identifiers
External DOI: https://doi.org/10.3389/fgene.2020.556259
This record's URL: https://www.repository.cam.ac.uk/handle/1810/312201
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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