Pf-HaploAtlas: an interactive web app for spatiotemporal analysis of Plasmodium falciparum genes

Abstract

Motivation: Monitoring the genomic evolution of Plasmodium falciparum-the most widespread and deadliest of the human-infecting malaria species-is critical for making decisions in response to changes in drug resistance, diagnostic test failures, and vaccine effectiveness. The MalariaGEN data resources are the world's largest whole genome sequencing databases for Plasmodium parasites. The size and complexity of such data is a barrier to many potential end users in both public health and academic research. A user-friendly method for accessing and exploring data on the genetic variation of P. falciparum would greatly enable efforts in studying and controlling malaria.

Results: We developed Pf-HaploAtlas, a web application enabling exploratory data analysis of genomic variation without requiring advanced technical expertise. The app provides analysis-ready data catalogues and visualizations of amino acid haplotypes for all 5102 core P. falciparum genes. Pf-HaploAtlas facilitates comprehensive spatial and temporal exploration of genes and variants of interest by using data from 16 203 samples, from 33 countries, and spread between the years 1984 and 2018. The scope of Pf-HaploAtlas will expand with each new MalariaGEN Plasmodium data release.

Availability and implementation: Pf-HaploAtlas is available online for public use at https://apps.malariagen.net/pf-haploatlas, which allows users to download the underlying amino acid haplotype data for further analyses, and its source code is freely available on GitHub under the MIT licence at https://github.com/malariagen/pf-haploatlas.

Figure 1.

Overview of the Pf-HaploAtlas app, and demonstration of its use for investigating aat1, a gene that has recently become of interest in malaria genomic surveillance. Panel A shows the Haplotype UpSet plot for aat1. The left-most haplotype, S258L, is the most prevalent and shows wide geographic distribution, as depicted by the wide variety of subpopulation colours. The cursor hovers over the second most frequent haplotype, F313S/Q454E, which is almost exclusively found in the eastern part of southeast Asia (AS-SE-E). Clicking on this haplotype generates the abacus plot (B) and the world map plot (C) directly below the Haplotype UpSet plot within the app. The abacus plot for F313S/Q454E highlights an evident increase in frequency in several locations across Laos, Cambodia, and Vietnam over the past two decades, as depicted by the gradient of increasing colour intensity from left to right (B). All images of plots have been edited to retain visual clarity within the manuscript. With all plots, hovering over data elements with the cursor provides more information.