udCluster analysis of Plasmodium RNA-seq time-course dataudidentifies stage-specific co-regulated biological processes and regulatory elements version 1; referees: 1 approved, 2 approved with reservations

摘要

In this study, we interpreted RNA-seq time-course data of three developmentaludstages of Plasmodium species by clustering genes based on similarities in theirudexpression profile without prior knowledge of the gene function. Functionaludenrichment of clusters of upregulated genes at specific time-points revealsudpotential targetable biological processes with information on their timings. Weudidentified common consensus sequences that these clusters shared asudpotential points of coordinated transcriptional control. Five cluster groupsudshowed upregulated profile patterns of biological interest. This included twoudclusters from the Intraerythrocytic Developmental Cycle (cluster 4 = 16 genes,udand cluster 9 = 32 genes), one from the sexual development stage (cluster 2 =ud851 genes), and two from the gamete-fertilization stage in the mosquito hostud(cluster 4 = 153 genes, and cluster 9 = 258 genes). The IDC expressed theudleast numbers of genes with only 1448 genes showing any significant activity ofudthe 5020 genes (~29%) in the experiment. Gene ontology (GO) enrichmentudanalysis of these clusters revealed a total of 671 uncharacterized genesudimplicated in 14 biological processes and components associated with theseudstages, some of which are currently being investigated as drug targets inudon-going research. Five putative transcription regulatory binding motifs sharedudby members of each cluster were also identified, one of which was alsoudidentified in a previous study by separate researchers. Our study showsudstage-specific genes and biological processes that may be important inudantimalarial drug research efforts. In addition, timed-coordinated control ofudseparate processes may explain the paucity of factors in parasites