title: Large-scale dynamic gene regulatory network inference combining differential equation models with local dynamic Bayesian network analysis.
abstract: BACKGROUND
  Reverse engineering gene regulatory networks, especially large size networks from time series gene expression data, remain a challenge to the systems biology community. In this article, a new hybrid algorithm integrating ordinary differential equation models with dynamic Bayesian network analysis, called Differential Equation-based Local Dynamic Bayesian Network (DELDBN), was proposed and implemented for gene regulatory network inference.
  
  
  RESULTS
  The performance of DELDBN was benchmarked with an in vivo dataset from yeast. DELDBN significantly improved the accuracy and sensitivity of network inference compared with other approaches. The local causal discovery algorithm implemented in DELDBN also reduced the complexity of the network inference algorithm and improved its scalability to infer larger networks. We have demonstrated the applicability of the approach to a network containing thousands of genes with a dataset from human HeLa cell time series experiments. The local network around BRCA1 was particularly investigated and validated with independent published studies. BRAC1 network was significantly enriched with the known BRCA1-relevant interactions, indicating that DELDBN can effectively infer large size gene regulatory network from time series data.
  
  
  BACKGROUND
  The R scripts are provided in File 3 in Supplementary Material.
  
  
  BACKGROUND
  zheng.li@monsanto.com; jingdong.liu@monsanto.com
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Monsanto Company, Mail zone CC1A, Chesterfield, MO 63017, USA. zheng.li@monsanto.com
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Arun
authors.initials: A
authors.lastname: Krishnan
authors.forename: Jingdong
authors.initials: J
authors.lastname: Liu
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D019398:Genes, BRCA1; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012680:Sensitivity and Specificity