Abstract
Despite significant progress in apicomplexan genome sequencing and genomics, the current list of experimentally validated transcription factors (TFs) in these genomes is incomplete and mainly consists of AP2 family of proteins, with only a limited number of non-AP2 family TFs and transcription-associated co-factors (TcoFs). We have performed a systematic bioinformatics-aided prediction of TFs and TcoFs in apicomplexan genomes and developed the ApicoTFdb database which consists of experimentally validated as well as computationally predicted TFs and TcoFs in 14 apicomplexan species. The predicted TFs are manually curated to complement the existing annotations. The current version of the database includes 1292 TFs which includes experimentally validated and computationally predicted TFs, representing 20 distinct families across 14 apicomplexan species. The predictions include TFs of TUB, NAC, BSD, HTH, Cupin/Jumonji, winged helix and FHA family proteins, not reported earlier as TFs in the genomes. Apart from TFs, ApicoTFdb also classifies TcoFs into three main subclasses: TRs, CRRs and RNARs, representing 2491 TcoFs in 14 apicomplexan species, are analyzed in this study. The database is designed to integrate different tools for comparative analysis. All entries in the database are dynamically linked with other databases, literature reference, protein–protein interactions, pathways and annotations associated with each protein. ApicoTFdb will be useful to the researchers interested in less-studied gene regulatory mechanisms mediating the complex life cycle of the apicomplexan parasites. The database will aid in the discovery of novel drug targets to much needed combat the growing drug resistance in the parasites.
Highlights
Transcription regulation is a key process that facilitates the cellular responses to different environmental conditions
There are many proteins known as transcriptionassociated co-factors (TcoFs) which do not bind to DNA but interact with transcription factors (TFs) for transcription regulations such as chromatin remodeling factor, controlling the direction of gene regulation by assisting general TFs [7]
For TcoF predictions, we performed GO-based analysis of each protein sequence to search for different classes of regulators, i.e. transcriptional regulators (TRs), chromatin regulators (CRRs) and RNA regulators (RNARs), among apicomplexans
Summary
Transcription regulation is a key process that facilitates the cellular responses to different environmental conditions. Only a limited number of TFs, mainly belonging to the AP2 family, are experimentally validated in the parasite [9] In virtue of their essential role in guiding the key cellular processes in the parasite’s life cycle involving multiple hosts, identification and characterization of novel TFs may provide deeper understanding of gene regulation in the parasite which may lead to identification of new drug targets. We are able to identify and report several new TFs and TcoFs belonging to diverse protein families among different apicomplexan species, including P. falciparum Using this information, we have developed ApicoTFdb—a novel web-based repository for hosting the classified list of apicomplexan regulators and information related to their domain architecture, molecular function(s), biological pathway(s) and interologs dynamically linked to related literature. We believe that the presented database would be extremely useful for the scientific community interested in deducing the regulatory molecules and their mechanism that governs the complex life cycle of any of these 14 different apicomplexan parasites
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