Scalable optimal Bayesian classification of single-cell trajectories under regulatory model uncertainty

Background

Biological networks describes the mechanisms which govern cellular functions. Temporal networks show how these networks evolve over time. Studying the temporal progression of network topologies is of utmost importance since it uncovers how a network evolves and how it resists to external stimuli and internal variations. Two temporal networks have co-evolving subnetworks if the evolving topologies of these subnetworks remain similar to each other as the network topology evolves over a period of time. In this paper, we consider the problem of identifying co-evolving subnetworks given a pair of temporal networks, which aim to capture the evolution of molecules and their interactions over time. Although this problem shares some characteristics of the well-known network alignment problems, it differs from existing network alignment formulations as it seeks a mapping of the two network topologies that is invariant to temporal evolution of the given networks. This is a computationally challenging problem as it requires capturing not only similar topologies between two networks but also their similar evolution patterns.

Results

We present an efficient algorithm, Tempo, for solving identifying co-evolving subnetworks with two given temporal networks. We formally prove the correctness of our method. We experimentally demonstrate that Tempo scales efficiently with the size of network as well as the number of time points, and generates statistically significant alignments—even when evolution rates of given networks are high. Our results on a human aging dataset demonstrate that Tempo identifies novel genes contributing to the progression of Alzheimer’s, Huntington’s and Type II diabetes, while existing methods fail to do so.

Conclusions

Studying temporal networks in general and human aging specifically using Tempo enables us to identify age related genes from non age related genes successfully. More importantly, Tempo takes the network alignment problem one huge step forward by moving beyond the classical static network models.