Network decomposition based large-scale reverse engineering of gene regulatory network
- Authors: Chowdhury, Ahsan , Chetty, Madhu
- Date: 2015
- Type: Text , Journal article
- Relation: Neurocomputing Vol. 160, no. (2015), p. 213-227
- Full Text: false
- Reviewed:
- Description: A Gene Regulatory Network (GRN) is the functional circuitry of a living organism that exhibits the regulatory relationships among genes of a cellular system at the gene level. In real-life biological networks, the number of genes present are very large exhibiting both, the instantaneous and time-delayed regulations. While our recent technique [1] addresses the modeling of time-delays occurring in genetic interactions, the issue of large-scale GRN modeling still remains. In this paper, we propose a novel methodology for large-scale modeling of GRNs by decomposing the GRN into two independent sub-networks utilizing its biological traits. Using the time-delayed S-system model [1], these two sub-networks are learnt separately and then combined to get the entire GRN. To speed up the inference mechanism, a cardinality-based fitness function, especially developed for inferring large-scale GRNs is proposed to allow incorporation of knowledge of maximum in-degree. A novel local-search method is also proposed to further facilitate the incorporation of biological knowledge by gene clustering and gene ranking. Experimental studies demonstrate that the proposed approach is successful in learning large genetic networks, currently not achievable with existing S-system based modeling approaches.
Adaptive regulatory genes cardinality for reconstructing genetic networks
- Authors: Chowdhury, Ahsan , Chetty, Madhu , Vinh, Nguyen
- Date: 2012
- Type: Text , Conference paper
- Relation: WCCI 2012 IEEE World Congress on Computational Intelligence
- Full Text: false
- Reviewed:
- Description: With the advent of microarray technology, researchers are able to determine cellular dynamics for thousands of genes simultaneously, thereby enabling reverse engineering of the gene regulatory network (GRN) from high-throughput time-series gene expression data. Amongst the various currently available models for inferring GRN, the S-System formalism is often considered as an excellent compromise between accuracy and mathematical tractability. In this paper, a novel approach for inferring GRN based on the decoupled S-System model, incorporating the new concept of adaptive regulatory genes cardinality, is proposed. Parameter learning for the S-System is carried out in an evolving manner using a versatile and robust Trigonometric Evolutionary Algorithm. The applicability and efficiency of the proposed method is studied using a well-known and widely studied synthetic network with various levels of noise, and excellent performance observed. Further, investigations of a 5 gene in-vivo synthetic biological network of Saccharomyces cerevisiae called IRMA, has succeeded in detecting higher number of correct regulations compared to other approaches reported earlier.