Abstract

Resistance in malaria is a growing concern affecting many areas of Sub-Saharan Africa and Southeast Asia. Since the emergence of artemisinin resistance in the late 2000s in Cambodia, research into the underlying mechanisms has been underway. The 2019 Malaria Challenge posited the task of developing computational models that address important problems in advancing the fight against malaria. The first goal was to accurately predict artemisinin drug resistance levels of Plasmodium falciparum isolates, as quantified by the IC 50. The second goal was to predict the parasite clearance rate of malaria parasite isolates based on in vitro transcriptional profiles. In this work, we develop machine learning models using novel methods for transforming isolate data and handling the tens of thousands of variables that result from these data transformation exercises. This is demonstrated by using massively parallel processing of the data vectorization for use in scalable machine learning. In addition, we show the utility of ensemble machine learning modeling for highly effective predictions of both goals of this challenge. This is demonstrated by the use of multiple machine learning algorithms combined with various scaling and normalization preprocessing steps. Then, using a voting ensemble, multiple models are combined to generate a final model prediction.

Highlights

  • Malaria is a serious disease caused by parasites belonging to the genus Plasmodium which are transmitted by Anopheles mosquitoes in the genus

  • The ‘Preprocess Data?’ parameter enables the scaling and imputation of the features in the data. Note that these models were evaluated using random sampling of the input training dataset provided by the DREAM Challenge, though the evaluation within the challenge was performed on an unlabelled testing dataset

  • A goal of this work is to understand genes important in the prediction of artemisinin resistance. The relationship of this use case to the first is that parasite clearance is a measure of the effectiveness of a treatment regimen

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Summary

Introduction

Malaria is a serious disease caused by parasites belonging to the genus Plasmodium which are transmitted by Anopheles mosquitoes in the genus. The World Health Organization (WHO) reports that there were 219 million cases of malaria in 2017 across 87 countries[1]. Plasmodium falciparum poses one of greatest health threats in Southeast Asia, being responsible for 62.8% of malaria cases in the region in 20171. Artemisinin-based therapies are among the best treatment options for malaria caused by P. falciparum[2]. The established pharmacodynamics benchmark for P. falciparum sensitivity to artemisinin-based therapy is the parasite clearance rate[5,6]. Resistance to artemisinin-based therapy is considered to be present with a parasite clearance rate greater than five hours[7]. By understanding the genetic factors that affect resistance in malaria, targeted development can occur in an effort to abate further resistance or infections of resistant strains

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