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Integrative transcriptomics and hypothesis-driven transfer machine learning reveal conserved and species-specific host-parasite dynamics across Leishmania species in THP-1 cells: a systematic review and meta-analysis

Al-Ghafli H, Alqurain A, Alzahrani FM, Elhadi N, Prajapati J, Nisar H

Frontiers in cellular and infection microbiology, 2026

Abstract

Introduction: Leishmaniasis is a vector-borne parasitic disease caused by protozoa of the genus Leishmania, characterized by clinical outcomes ranging from self-limiting cutaneous lesions to fatal visceral disease. Disease progression is multifactorial and is largely shaped by interactions between the parasite and host macrophages, as well as by other host- and pathogen-related factors. Although transcriptomic studies have provided insights into these interactions, differences in experimental design, parasite species, and analytical workflows have limited cross-study comparisons and the identification of conserved molecular responses.

Methods: A systematic review was conducted following PRISMA guidelines to identify publicly available RNA-seq datasets of Leishmania-infected THP-1 macrophages. Raw sequencing data from eligible studies were reanalyzed using a unified bioinformatics pipeline incorporating standardized quality control, differential gene expression analysis, and batch-effect correction to enable robust cross-study integration. Comparative analyses were performed across infection stages and between L. infantum and L. amazonensis. The integrated transcriptomic dataset was subsequently used to develop a hypothesis-driven transfer learning framework to evaluate the feasibility of predicting L. amazonensis parasite gene expression at 96 hours post-infection (hpi) from experimentally generated 24 hpi transcriptomic profiles.

Results: Integrated analysis revealed a…

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Evidence Hub reads this as a meta-analysis, done in cell cultures (in vitro) and computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.

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