Gene-Protein networks in Drosophila Melanogaster

Inigo San Gil 1, Kevin White2, Joel Bader, Tong-Ruei Li, Yale University;, Yale University

Genome-wide networks composed of interaction maps between proteins and genes have been created using extensive gene and protein data sources for Drosophila melanogaster. We considered three data sets in building these networks. First, we analyzed a developmental time course of gene expression consisting of eleven points spanning the larvae to pupariation stages (Li and White, Dev. Cell in press). This study focused on one tissue composed of two main cell types, the midgut. One cell type undergoes proliferation during this stage of development while the other undergoes programmed cell death. From the 14k genes that comprise the Drosophila melanogaster genome, about 5,000 showed significant changes in gene expression. A gene expression cross correlation was computed for each gene pair in this data set, and matches with other gene pathways and protein interactions were sought. Second, gene expression patterns were examined during the entire life cycle using whole animals (Arbeitman et al. Science 2002). These data are a composite of expression from many tissues and organs, and they were readily analyzed with our cross-correlation approach due to the comprehensive nature of the data sampling (74 developmental time points). Using cross-correlation coefficients, a network of interacting gene products was derived. Third,the results from gene expression analysis were combined with a genome-wide yeast two hybrid (Y2H) protein interaction data set (Bader et al. in preparation). This allowed an additional dimension to be added to our networks. These preliminary networks show a rich network of connections between genes and proteins, and presents hundreds of new hypotheses begging to be explored. However, we present details from several protein families that were of particular focus in our study. We have mapped protein families based on a database of alignments and HMMs (Pfam), genes and proteins involved in cell cycle, and those involved in the ecdysone developmental network.