Tailored graphical lasso for data integration in gene network reconstruction.


Type
Article
Change log
Authors
Lingjærde, Camilla  ORCID logo  https://orcid.org/0000-0003-2701-5686
Lien, Tonje G 
Borgan, Ørnulf 
Bergholtz, Helga 
Glad, Ingrid K 
Abstract

BACKGROUND: Identifying gene interactions is a topic of great importance in genomics, and approaches based on network models provide a powerful tool for studying these. Assuming a Gaussian graphical model, a gene association network may be estimated from multiomic data based on the non-zero entries of the inverse covariance matrix. Inferring such biological networks is challenging because of the high dimensionality of the problem, making traditional estimators unsuitable. The graphical lasso is constructed for the estimation of sparse inverse covariance matrices in such situations, using [Formula: see text]-penalization on the matrix entries. The weighted graphical lasso is an extension in which prior biological information from other sources is integrated into the model. There are however issues with this approach, as it naïvely forces the prior information into the network estimation, even if it is misleading or does not agree with the data at hand. Further, if an associated network based on other data is used as the prior, the method often fails to utilize the information effectively. RESULTS: We propose a novel graphical lasso approach, the tailored graphical lasso, that aims to handle prior information of unknown accuracy more effectively. We provide an R package implementing the method, tailoredGlasso. Applying the method to both simulated and real multiomic data sets, we find that it outperforms the unweighted and weighted graphical lasso in terms of all performance measures we consider. In fact, the graphical lasso and weighted graphical lasso can be considered special cases of the tailored graphical lasso, and a parameter determined by the data measures the usefulness of the prior information. We also find that among a larger set of methods, the tailored graphical is the most suitable for network inference from high-dimensional data with prior information of unknown accuracy. With our method, mRNA data are demonstrated to provide highly useful prior information for protein-protein interaction networks. CONCLUSIONS: The method we introduce utilizes useful prior information more effectively without involving any risk of loss of accuracy should the prior information be misleading.

Description
Keywords
Cancer genomics, Gene networks, Genomics, Graphical lasso, High-dimensional inference, Integrative analysis, Multiomics, Network models, Protein–protein interaction networks, Weighted graphical lasso, Algorithms, Gene Regulatory Networks, Genomics, Normal Distribution, Protein Interaction Maps
Journal Title
BMC Bioinformatics
Conference Name
Journal ISSN
1471-2105
1471-2105
Volume Title
22
Publisher
Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MCUU00002/10)