Mukherjee Parnika, Burgio Gaétan, Heitlinger Emanuel
Department of Molecular Parasitology, Humboldt University, Berlin, Germany.
Research Group Ecology and Evolution of Molecular Parasite-Host Interactions, Leibniz-Institute for Zoo and Wildlife Research (IZW), Berlin, Germany.
mSystems. 2021 Apr 20;6(2):e00182-21. doi: 10.1128/mSystems.00182-21.
Dual RNA sequencing (RNA-Seq) is the simultaneous transcriptomic analysis of interacting symbionts, for example, in malaria. Potential cross-species interactions identified by correlated gene expression might highlight interlinked signaling, metabolic, or gene regulatory pathways in addition to physically interacting proteins. Often, malaria studies address one of the interacting organisms-host or parasite-rendering the other "contamination." Here we perform a meta-analysis using such studies for cross-species expression analysis. We screened experiments for gene expression from host and Out of 171 studies in , , and , we identified 63 potential studies containing host and parasite data. While 16 studies (1,950 samples) explicitly performed dual RNA-Seq, 47 (1,398 samples) originally focused on one organism. We found 915 experimental replicates from 20 blood studies to be suitable for coexpression analysis and used orthologs for meta-analysis across different host-parasite systems. Centrality metrics from the derived gene expression networks correlated with gene essentiality in the parasites. We found indications of host immune response to elements of the protein degradation system, an antimalarial drug target. We identified well-studied immune responses in the host with our coexpression networks, as our approach recovers known broad processes interlinked between hosts and parasites in addition to individual host and parasite protein associations. The set of core interactions represents commonalities between human malaria and its model systems for prioritization in laboratory experiments. Our approach might also allow insights into the transferability of model systems for different pathways in malaria studies. Malaria still causes about 400,000 deaths a year and is one of the most studied infectious diseases. The disease is studied in mice and monkeys as lab models to derive potential therapeutic intervention in human malaria. Interactions between spp. and its hosts are either conserved across different host-parasite systems or idiosyncratic to those systems. Here we use correlation of gene expression from different RNA-Seq studies to infer common host-parasite interactions across human, mouse, and monkey studies. First, we find a set of very conserved interactors, worth further scrutiny in focused laboratory experiments. Second, this work might help assess to which extent experiments and knowledge on different pathways can be transferred from models to humans for potential therapy.
双RNA测序（RNA-Seq）是对相互作用的共生体进行同步转录组分析，例如在疟疾研究中。通过相关基因表达确定的潜在跨物种相互作用，除了物理上相互作用的蛋白质外，还可能突出相互关联的信号传导、代谢或基因调控途径。通常，疟疾研究只关注相互作用的生物体之一——宿主或寄生虫——而将另一个视为“污染物”。在这里，我们使用此类研究进行荟萃分析以进行跨物种表达分析。我们筛选了关于宿主和寄生虫基因表达的实验。在[具体数据库1]、[具体数据库2]和[具体数据库3]中的171项研究中，我们确定了63项可能包含宿主和寄生虫数据的研究。其中16项研究（1950个样本）明确进行了双RNA测序，47项研究（1398个样本）最初聚焦于一种生物体。我们发现来自20项血液研究的915个实验复制品适合进行共表达分析，并使用直系同源基因进行跨不同宿主 - 寄生虫系统的荟萃分析。从衍生的基因表达网络中得出的中心性指标与寄生虫中的基因必需性相关。我们发现宿主对蛋白质降解系统元件存在免疫反应的迹象，蛋白质降解系统是一个抗疟药物靶点。通过我们的共表达网络，我们在宿主中识别出了经过充分研究的免疫反应，因为我们的方法除了能恢复宿主和寄生虫个体蛋白质关联外，还能发现宿主和寄生虫之间相互关联的已知广泛过程。这组核心相互作用代表了人类疟疾及其模型系统之间的共性，可用于实验室实验中的优先级排序。我们的方法还可能有助于深入了解疟疾研究中不同途径模型系统的可转移性。疟疾每年仍导致约40万人死亡，是研究最多的传染病之一。在小鼠和猴子身上作为实验室模型对该疾病进行研究，以推导对人类疟疾的潜在治疗干预措施。疟原虫与宿主之间的相互作用在不同宿主 - 寄生虫系统中要么是保守的，要么是这些系统特有的。在这里，我们利用不同RNA测序研究中的基因表达相关性来推断人类、小鼠和猴子研究中常见的宿主 - 寄生虫相互作用。首先，我们发现了一组非常保守的相互作用因子，值得在重点实验室实验中进一步研究。其次，这项工作可能有助于评估不同途径的实验和知识在多大程度上可以从模型转移到人类身上以用于潜在治疗。
