Comparative single-cell transcriptional atlases of Babesia species reveal conserved and species-specific expression profiles

Babesia is a genus of apicomplexan parasites that infect red blood cells in vertebrate hosts. Pathology occurs during rapid replication cycles in the asexual blood stage of infection. Current knowledge of Babesia replication cycle progression and regulation is limited and relies mostly on comparativ...

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Bibliographic Details
Published in:PLoS biology 2022-09, Vol.20 (9), p.e3001816
Main Authors: Rezvani, Yasaman, Keroack, Caroline D, Elsworth, Brendan, Arriojas, Argenis, Gubbels, Marc-Jan, Duraisingh, Manoj T, Zarringhalam, Kourosh
Format: Article
Language:English
Subjects:
Algorithms
Applications programs
Approximation
Babesia
Babesia - genetics
Biology and Life Sciences
Blood
Blood cells
Cell cycle
Cell division
Cluster analysis
Clustering
Comparative studies
Datasets
Deoxyribonucleic acid
Divergence
DNA
DNA biosynthesis
Epigenetics
Erythrocytes
Erythrocytes - parasitology
Gene expression
Gene sequencing
Genetic aspects
Mathematical analysis
Medicine and Health Sciences
Methods and Resources
Molecular evolution
Natural history
Parasites
Parasitological research
Red blood cells
Replication
RNA sequencing
Software
Species
Synchronism
Time synchronization
Transcription factors
Transcription Factors - genetics
Transcriptome - genetics
Transcriptomics
Vertebrates
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Summary:Babesia is a genus of apicomplexan parasites that infect red blood cells in vertebrate hosts. Pathology occurs during rapid replication cycles in the asexual blood stage of infection. Current knowledge of Babesia replication cycle progression and regulation is limited and relies mostly on comparative studies with related parasites. Due to limitations in synchronizing Babesia parasites, fine-scale time-course transcriptomic resources are not readily available. Single-cell transcriptomics provides a powerful unbiased alternative for profiling asynchronous cell populations. Here, we applied single-cell RNA sequencing to 3 Babesia species (B. divergens, B. bovis, and B. bigemina). We used analytical approaches and algorithms to map the replication cycle and construct pseudo-synchronized time-course gene expression profiles. We identify clusters of co-expressed genes showing "just-in-time" expression profiles, with gradually cascading peaks throughout asexual development. Moreover, clustering analysis of reconstructed gene curves reveals coordinated timing of peak expression in epigenetic markers and transcription factors. Using a regularized Gaussian graphical model, we reconstructed co-expression networks and identified conserved and species-specific nodes. Motif analysis of a co-expression interactome of AP2 transcription factors identified specific motifs previously reported to play a role in DNA replication in Plasmodium species. Finally, we present an interactive web application to visualize and interactively explore the datasets.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3001816