Bottom-up GGM algorithm for constructing multilayered hierarchical gene regulatory networks that govern biological pathways or processes

Authors

Sapna Kupari, Michigan Technological University
Wenping Deng, Michigan Technological University
Chathura J. Gunasekara, Michigan Technological UniversityFollow
Vincent Chiang, North Carolina State University at Raleigh
Huann-sheng Chen, National Institutes of Health
Hairong Wei, Michigan Technological UniversityFollow
et. al.

Document Type

Article

Publication Date

3-18-2016

Department

College of Forest Resources and Environmental Science; Center for Data Sciences

Abstract

Background: Multilayered hierarchical gene regulatory networks (ML-hGRNs) are very important for understanding genetics regulation of biological pathways. However, there are currently no computational algorithms available for directly building ML-hGRNs that regulate biological pathways.

Results: A bottom-up graphic Gaussian model (GGM) algorithm was developed for constructing ML-hGRN operating above a biological pathway using small- to medium-sized microarray or RNA-seq data sets. The algorithm first placed genes of a pathway at the bottom layer and began to construct an ML-hGRN by evaluating all combined triple genes: two pathway genes and one regulatory gene. The algorithm retained all triple genes where a regulatory gene significantly interfered two paired pathway genes. The regulatory genes with highest interference frequency were kept as the second layer and the number kept is based on an optimization function. Thereafter, the algorithm was used recursively to build a ML-hGRN in layer-by-layer fashion until the defined number of layers was obtained or terminated automatically.

Conclusions: We validated the algorithm and demonstrated its high efficiency in constructing ML-hGRNs governing biological pathways. The algorithm is instrumental for biologists to learn the hierarchical regulators associated with a given biological pathway from even small-sized microarray or RNA-seq data sets.

Publisher's Statement

© 2016 Kumari et al. Article deposited here in compliance with publisher policies. Publisher's version of record: https://doi.org/10.1186/s12859-016-0981-1

Publication Title

BMC Bioinformatics

Recommended Citation

Kupari, S., Deng, W., Gunasekara, C. J., Chiang, V., Chen, H., Wei, H., & et. al. (2016). Bottom-up GGM algorithm for constructing multilayered hierarchical gene regulatory networks that govern biological pathways or processes. BMC Bioinformatics, 17. http://doi.org/10.1186/s12859-016-0981-1
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/1002

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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