Title
Formal Analysis of Network Motifs Links Structure to Function in Biological Programs
Abstract
AbstractA recurring set of small sub-networks have been identified as the building blocks of biological networks across diverse organisms. These network motifs are associated with certain dynamic behaviors and define key modules that are important for understanding complex biological programs. Besides studying the properties of motifs in isolation, current algorithms typically evaluate the occurrence frequency of a specific motif in a given biological network compared to that in random networks of similar structure. However, it remains challenging to relate the structure of motifs to the observed and expected behavior of the larger, more complex network they are contained within. This problem is compounded as even the precise structure of most biological networks remains largely unknown. Previously, we developed a formal reasoning approach enabling the synthesis of biological networks capable of reproducing some experimentally observed behavior. Here, we extend this approach to allow reasoning over the requirement for specific network motifs as a way of explaining how these behaviors arise. We illustrate the approach by analyzing the motifs involved in sign-sensitive delay and pulse generation. We demonstrate the scalability and biological relevance of the approach by studying the previously defined networks governing myeloid differentiation, the yeast cell cycle, and naïve pluripotency in mouse embryonic stem cells, revealing the requirement for certain motifs in these systems.
Year
DOI
Venue
2021
10.1109/TCBB.2019.2948157
IEEE/ACM Transactions on Computational Biology and Bioinformatics
Keywords
DocType
Volume
Biological interaction networks, biological programs, network motifs, synthesis, satisfiability modulo theories (SMT), formal reasoning
Journal
18
Issue
ISSN
Citations 
1
1545-5963
0
PageRank 
References 
Authors
0.34
0
3
Name
Order
Citations
PageRank
Sara-Jane Dunn1355.02
Hillel Kugler257735.87
Boyan Yordanov31108.67