Abstract: Bioinformatics is a powerful way to use computational techniques to gain better understanding of biological processes. In many cases it is desirable to analyze genotypes and phenotypes jointly. There have been a huge amount of existing work on genotype data analysis; in recent years, high-throughput phenotype screening that involves systematic analysis of microscopic images (thus called “Bioimage Informatics”) and other types of data has become more and more promising. Here I will discuss several examples on how to (1) build a single cell resolution gene expression map for C. elegans and detect new cell types, and (2) develop a pipeline of tools to understand the structures of a complicated fruit fly’s brain. I will also discuss our high-performance image computing platform, V3D (http://penglab.janelia.org/proj/v3d), that has been used in several challenging high-throughput bioimage informatics applications.