MALBoost: a web-based application for gene regulatory network analysis in Plasmodium falciparum

• Published in: Malaria journal Vol. 20; no. 1; pp. 1 - 317
• Main Authors: van Wyk, Roelof, van Biljon, Riëtte, Birkholtz, Lyn-Marie
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 14.07.2021; BioMed Central; BMC
• Subjects: Algorithms; Artificial intelligence; Binding sites; Construction; Datasets; Gene expression; Gene regulation; Gene regulatory network; Genetic aspects; Genetic regulation; Genomes; Health aspects; Human diseases; Machine learning; Malaria; Methodology; Parasites; Plasmodium falciparum; Queuing; Servers; Technology application; Templates; Transcription; Transcription factors; Transcriptomes; Transcriptomics; Vector-borne diseases; Web applications; United States; South Africa
• ISSN: 1475-2875; 1475-2875
• DOI: 10.1186/s12936-021-03848-2

Abstract Background Gene Regulatory Networks (GRN) produce powerful insights into transcriptional regulation in cells. The power of GRNs has been underutilized in malaria research. The Arboreto library was incorporated into a user-friendly web-based application for malaria researchers ( http://malboost.bi.up.ac.za ). This application will assist researchers with gaining an in depth understanding of transcriptomic datasets. Methods The web application for MALBoost was built in Python-Flask with Redis and Celery workers for queue submission handling, which execute the Arboreto suite algorithms. A submission of 5–50 regulators and total expression set of 5200 genes is permitted. The program runs in a point-and-click web user interface built using Bootstrap4 templates. Post-analysis submission, users are redirected to a status page with run time estimates and ultimately a download button upon completion. Result updates or failure updates will be emailed to the users. Results A web-based application with an easy-to-use interface is presented with a use case validation of AP2-G and AP2-I. The validation set incorporates cross-referencing with ChIP-seq and transcriptome datasets. For AP2-G, 5 ChIP-seq targets were significantly enriched with seven more targets presenting with strong evidence of validated targets. Conclusion The MALBoost application provides the first tool for easy interfacing and efficiently allows gene regulatory network construction for Plasmodium . Additionally, access is provided to a pre-compiled network for use as reference framework. Validation for sexually committed ring-stage parasite targets of AP2-G, suggests the algorithm was effective in resolving “traditionally” low-level signatures even in bulk RNA datasets.