Rapid Reconstruction of Time-Varying Gene Regulatory Networks

Rapid advancements in high-throughput technologies have resulted in genome-scale time series datasets. Uncovering the temporal sequence of gene regulatory events, in the form of time-varying gene regulatory networks (GRNs), demands computationally fast, accurate, and scalable algorithms. The existing algorithms can be divided into two categories: ones that are time-intensive and hence unscalable; and others that impose structural constraints to become scalable. In this paper, a novel algorithm, namely 'an algorithm for reconstructing Time-varying Gene regulatory networks with Shortlisted candidate regulators' (TGS), is proposed. TGS is time-efficient and does not impose any structural constraints. Moreover, it provides such flexibility and time-efficiency, without losing its accuracy. TGS consistently outperforms the state-of-the-art algorithms in true positive detection, on three benchmark synthetic datasets. However, TGS does not perform as well in false positive rejection. To mitigate this issue, TGS+ is proposed. TGS+ demonstrates competitive false positive rejection power, while maintaining the superior speed and true positive detection power of TGS. Nevertheless, the main memory requirements of both TGS variants grow exponentially with the number of genes, which they tackle by restricting the maximum number of regulators for each gene. Relaxing this restriction remains a challenge as the actual number of regulators is not known a priori.