Publicly available transcriptomes provide the opportunity for dual RNA-Seq meta-analysis inPlasmodiuminfection

Abstract

1Dual RNA-Seq is the simultaneous retrieval and analysis of host and pathogen transcriptomes. 2 It follows the rationale that cross-species interactions determine both pathogen virulence and host 3 tolerance, resistance or susceptibility. Correlated gene expression might help identify interlinked 4 signaling, metabolic or gene regulatory pathways in addition to potentially physically interacting 5 proteins. Numerous studies have used RNA-Seq to investigate Plasmodium infection with a focus 6 on only one organism, either the host or the parasite.7Here we propose a meta-analysis approach for dual RNA-Seq. We screened malaria transcrip-8 tome experiments for gene expression data from both Plasmodium and its host. Out of 105 malaria 9 studies in Homo sapiens, Macaca mulatta and Mus musculus, we identified 56 studies with the 10 potential to provide host and parasite data. While 15 studies (1,935 total samples) of these 56 11 explicitly aimed to generate dual RNA-Seq data, 41 (1,129 samples) had an original focus on either 12 the host or the parasite. We show that a total of up to 2,530 samples are suitable for dual RNA-Seq 13 analysis providing an unexplored potential for meta-analysis. 14 We argue that the multitude of variations in experimental conditions should help narrow down 15 a conserved core of cross-species interactions. Different hosts are infected by evolutionarily diverse 16 species of the genus Plasmodium. We propose to overlay interaction networks of different host-17 parasite systems based on orthologous genes. This might allow us to gauge the applicability of 18 model systems for different pathways in malaria infection and to address the evolution of parasite-19 host interactions.20 Word count: 2836, Target journal word limit: 3000 22 23Transcriptomes are often analyzed as a first attempt to understand cellular and organismic events, because a 24 comprehensive profile of RNA expression can be obtained at a reasonable cost and with high technical accuracy 25 [37]. Microarrays dominated transcriptomics since 1995 [11, 22, 44]. Microarrays quantify gene expression 26 based on hybridization of a target sequence to an immobilized probe of known sequence. Technical difficulties 27 associated with microarrays lie in probe-selection, cross-hybridization, and design cost of custom chips [51]. RNA 28 sequencing (RNA-Seq) eliminates these difficulties and provides deep and accurate expression estimates for all 29 RNAs in a sample. RNA-Seq has thus replaced microarrays as the predominant tool for transcriptomics [37,50]. 30RNA-Seq assesses host and parasite transcriptomes simultaneously, if RNA of both organisms is contained 31 in a sample. It has been proposed to analyze the transcriptomes of both organisms involved in an infection 32 as pathogen virulence in an infectious disease is often a result of interlinked processes of host and pathogen 33 (host-pathogen interactions) [32, 50, 51]. 34In case of malaria, unlike in bacterial infections, both the pathogen and the host are eukaryotic organisms 35 with sim...

Immunogenetic response to a malaria-like parasite in a wild primate

“…Evidence of this lengthy battle is evident from scars in the human genome, as malaria has exerted one of the strongest selection pressures on the human immune system (Kwiatkowski, 2005; Kariuki and Williams, 2020). Recent investigations simultaneously assaying human and malaria gene expression in the blood have illuminated the genetic architecture of this host-parasite interaction, permitting fundamental insight into the immunology of this disease (Yamagishi et al, 2014; Otto et al, 2018; Lee et al, 2018; Mukherjee and Heitlinger, 2019). However, a full understanding of the adaptive human immunogenetic response to malaria requires comparative data from closely related primates.…”