Functional Genome Annotation by Combined Analysis across Microarray Studies of Trypanosoma brucei

摘要

The impact of the trypanosomatid genome sequencing projects, especially Trypanosoma brucei, Trypanosoma cruzi, and Leishmania species, has been substantial. However, significant numbers of hypothetical or conserved hypothetical trypanosomatid-specific genes remain uncharacterized with possible roles in infectivity and disease. The genes in trypanosomatids are organized into large multigenic clusters that are transcribed as polycistronic transcription units, thus limiting gene regulation mainly to the post-transcriptional level. In this study, we examined three independent DNA microarray studies of T. brucei, and found that mRNA abundances of functionally related T. brucei genes are co-regulated, most probably via post-transcriptional events. We then used this property of functionally related genes to predict the functions of hypothetical genes in T. brucei. The predictions were further improved by including DNA microarray studies from the closely related trypanosomatid Leishmania infantum, suggesting that parallel transcript profiling of trypanosomatids will be of considerable potential for refining gene function predictions in these organisms. Furthermore, we found that potential regulatory elements within untranslated regions of RNA transcripts can be predicted based on combined expression data from different microarray studies. Overall, this approach contributes to a better understanding of the mechanisms underlying gene regulation and function in trypanosomatids.