Peng Liu

Motivation Large-scale gene expression studies allow gene network construction to uncover associations among genes. To study direct associations among genes, partial correlation-based networks are preferred over marginal correlations. However, FDR control for partial correlation-based network construction is not well-studied. In addition, currently available partial correlation-based methods cannot take existing biological knowledge to help network construction while controlling FDR. Results In this paper, we propose a method called Partial Correlation Graph with Information Incorporation (PCGII). PCGII estimates partial correlations between each pair of genes by regularized node-wise regression that can incorporate prior knowledge while controlling the effects of all other genes. It handles high-dimensional data where the number of genes can be much larger than the sample size and controls FDR at the same time. We compare PCGII with several existing approaches through extensive simulation studies and demonstrate that PCGII has better FDR control and higher power. We apply PCGII to a plant gene expression dataset where it recovers confirmed regulatory relationships and a hub node, as well as several direct associations that shed light on potential functional relationships in the system. We also introduce a method to supplement observed data with a pseudogene to apply PCGII when no prior information is available, which also allows checking FDR control and power for real data analysis. Availability and implementation R package is freely available for download at https://cran.r-project.org/package=PCGII.

NAKED ENDOSPERM1 (NKD1), NKD2, and OPAQUE2 (O2) are transcription factors important for cell patterning and nutrient storage in maize (Zea mays) endosperm. To study the complex regulatory interrelationships among these 3 factors in coregulating gene networks, we developed a set of nkd1, nkd2, and o2 homozygous lines, including all combinations of mutant and wild-type genes. Among the 8 genotypes tested, we observed diverse phenotypes and gene interactions affecting cell patterning, starch content, and storage proteins. From ∼8 to ∼16 d after pollination, maize endosperm undergoes a transition from cellular development to nutrient accumulation for grain filling. Gene network analysis showed that NKD1, NKD2, and O2 dynamically regulate a hierarchical gene network during this period, directing cellular development early and then transitioning to constrain cellular development while promoting the biosynthesis and storage of starch, proteins, and lipids. Genetic interactions regulating this network are also dynamic. The assay for transposase-accessible chromatin using sequencing (ATAC-seq) showed that O2 influences the global regulatory landscape, decreasing NKD1 and NKD2 target site accessibility, while NKD1 and NKD2 increase O2 target site accessibility. In summary, interactions of NKD1, NKD2, and O2 dynamically affect the hierarchical gene network and regulatory landscape during the transition from cellular development to grain filling in maize endosperm.