How to mine the gene regulatory relationship and construct gene regulatory network (GRN) is of utmost interest within the whole biological community, however, which has been consistently a challenging problem since the tremendous complexity in cellular systems. In present work, we construct gene regulatory network using an improved three-phase dependency analysis algorithm (TPDA) Bayesian network learning method, which includes the steps of Drafting, Thickening, and Thinning. In order to solve the problem of learning result is not reliable due to the high order conditional independence test, we use the entropy estimation approach of Gaussian kernel probability density estimator to calculate the (conditional) mutual information between genes. The experiment on the public benchmark data sets show the improved method outperforms the other nine kinds of Bayesian network learning methods when to process the data with large sample size, with small number of discrete values, and the frequency of different discrete values is about same. In addition, the improved TPDA method was further applied on a real large gene expression data set on RNA-seq from a global collection with 368 elite maize inbred lines. Experiment results show it performs better than the original TPDA method and the other nine kinds of Bayesian network learning algorithms significantly.

SUMMARY: CRISPR-Local is a high-throughput local tool for designing single-guide RNAs (sgRNAs) in plants and other organisms that factors in genetic variation and is optimized to generate genome-wide sgRNAs. CRISPR-Local outperforms other sgRNA design tools in the following respects: (i) designing sgRNAs suitable for non-reference varieties; (ii) screening for sgRNAs that are capable of simultaneously targeting multiple genes; (iii) saving computational resources by avoiding repeated calculations from multiple submissions and (iv) running offline, with both command-line and graphical user interface modes and the ability to export multiple formats for further batch analysis or visualization. We have applied CRISPR-Local to 71 public plant genomes, using both CRISPR/Cas9 and CRISPR/cpf1 systems. AVAILABILITY AND IMPLEMENTATION: CRISPR-Local can be freely downloaded from http://crispr.hzau.edu.cn/CRISPR-Local/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.