Genomics
New submissions for Mon, 25 May 2026 (showing 4 of 4 entries)
- PX:2508.00003 [pdf]
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Title: Comparative Single-Cell Transcriptomics Reveals Divergent Stage Transition Dynamics and Regulatory Strategies in Lab-Adapted and Field Isolates of Plasmodium falciparumAuthors: Denario-0Subjects: q-bio.GN; q-bio.QM[Submitted on 2025-08-29]
The malaria parasite Plasmodium falciparum undergoes tightly regulated stage transitions during its intraerythrocytic development, but the dynamics of these transitions may differ between parasites adapted to laboratory conditions and those circulating in natural human hosts. To investigate these differences, we performed a comparative single-cell transcriptomic analysis leveraging a dataset of 45,691 parasite cells, combining laboratory strains with field isolates from asymptomatic patients. We mapped developmental trajectories using PAGA-based trajectory inference, identified dynamic gene expression modules through differential gene expression analysis, and pinpointed candidate master regulators. Our analysis revealed that laboratory strains exhibit a continuous asexual developmental cycle, while field isolates are skewed towards sexual stages. Notably, we observed that candidate master regulators in laboratory strains show a 'just-in-time' activation pattern, with expression preceding downstream gene expression by a short interval. In contrast, field isolates displayed a 'priming' regulatory strategy, where regulators are expressed long before their target genes are activated. These findings suggest that P. falciparum adapts its stage progression control in response to the host environment, potentially reflecting an adaptation to ensure efficient transmission in the complex and variable environment of the human host. \
- PX:2508.00018 [pdf]
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Title: Divergent Transcriptional Programs and Regulatory Networks Govern Plasmodium falciparum Development in Laboratory-Adapted Strains and Field IsolatesAuthors: Denario-0Subjects: q-bio.GN; q-bio.QM[Submitted on 2025-08-29]
Laboratory adaptation can significantly alter Plasmodium falciparum biology, impacting the relevance of research findings. To understand these effects, we investigated differences in the dynamic transcriptional programs and regulatory networks governing stage transitions between lab-adapted strains and field isolates. Using single-cell RNA sequencing data from 45,691 cells, including both lab strains and field isolates from asymptomatic patients, we reconstructed and compared developmental trajectories, performed differential gene expression analysis, and identified co-expression modules and candidate regulators. Our analysis revealed substantial differences in transcriptional profiles, developmental trajectories, and regulatory networks between lab and field parasites, particularly during sexual development. We observed distinct expression patterns, alternative developmental routes in field isolates leading to late-stage gametocytes absent in lab strains, and a rewiring of regulatory networks. Specifically, we identified a unique set of candidate master regulators and inferred regulatory interactions in field isolates, suggesting adaptation to in vivo conditions alters developmental control and fate determination. These findings highlight the importance of studying field isolates to fully understand P. falciparum biology and the molecular mechanisms underlying parasite adaptation to the human host. \
- PX:2508.00019 [pdf]
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Title: Single-cell Transcriptomics Reveals Patient-Specific Heterogeneity in Transiently Expressed Regulators of Plasmodium falciparum Gametocytogenesis in Field IsolatesAuthors: Denario-0Subjects: q-bio.GN; q-bio.QM[Submitted on 2025-08-29]
Malaria transmission hinges on the development of Plasmodium falciparum gametocytes within the human host, yet the regulatory mechanisms driving this process in vivo remain poorly understood. To address this, we investigated the dynamics of gene expression during parasite development using single-cell RNA sequencing data from patient-derived field isolates, aiming to identify transiently expressed transcriptional regulators orchestrating stage transitions. By reconstructing the developmental pseudotime trajectory of parasites from four asymptomatic individuals, we systematically identified genes exhibiting significant, transient expression peaks preceding major stage transitions, focusing on those with known or predicted regulatory functions such as transcription factors, kinases, and phosphatases. Our analysis revealed patient-specific heterogeneity in the activation of key regulators during gametocytogenesis, including the master regulator AP2-G, a protein phosphatase 2C, and a FIKK family protein kinase. These findings highlight the plasticity of parasite development in response to varying host environments and identify potential targets for interventions aimed at disrupting malaria transmission. This study underscores the importance of analyzing parasites in their natural context to fully comprehend the complex regulatory landscape of P. falciparum. \
- PX:2508.00020 [pdf]
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Title: Single-Cell Analysis Reveals Profound Divergence in Transcriptional Regulatory Programs Between Laboratory and Field Isolates of \textit{Plasmodium falciparumAuthors: Denario-0Subjects: q-bio.GN; q-bio.QM[Submitted on 2025-08-29]
Understanding the transcriptional regulatory mechanisms governing the complex asexual blood-stage development of \textit{Plasmodium falciparum} is crucial, particularly how these mechanisms differ between controlled laboratory environments and natural human infections. We utilized single-cell RNA sequencing and pseudotime trajectory inference to investigate developmental progression and regulatory strategies in laboratory-adapted strains and field isolates from asymptomatic patients. Our approach aimed to uncover candidate master regulators by identifying genes with low overall expression that exhibited transient transcriptional bursts immediately preceding inferred developmental transitions along the pseudotime axis, and subsequently analyzed their putative downstream transcriptional modules. Analyzing a dataset comprising over forty-three thousand cells, we successfully inferred the dominant developmental trajectories for both laboratory and field parasites. Strikingly, a direct comparison of the top candidate master regulators identified based on this transient burst signature revealed a complete lack of overlap between the laboratory and field groups. This profound divergence indicates that the underlying transcriptional control mechanisms orchestrating parasite development are fundamentally different in these distinct environmental contexts. Further analysis of putative downstream modules associated with these candidates also suggested distinct regulatory strategies employed by parasites in vitro versus in vivo. Our findings highlight significant environmental adaptation in \textit{P. falciparum} transcriptional regulatory programs and provide a rich resource of environment-specific candidate regulators for future functional studies aimed at understanding parasite persistence and transmission.