Authors

Discussion

Introduction Schistosomiasis, caused by blood flukes of the genus Schistosoma, affects over 240 million people worldwide and remains a major Neglected Tropical Disease, particularly in sub-Saharan Africa, Southeast Asia, and parts of South America¹. Chronic infection in the human definitive host leads to substantial morbidity driven by complex host-parasite interactions². The parasite undergoes an elaborate life cycle, transitioning through distinct environmental and host niches, each requiring tightly regulated stage-specific genomic and transcriptomic programs³. Indeed, the parasite exhibits complex gene regulation and stage-specific transcription throughout its life cycle, enabling adaptation, modulate host-pathogen immune responses, and reproduction^3-5. A key mechanism underlying this regulation is alternative splicing, which expands transcript diversity by generating multiple isoforms, that may influence parasite development, pathogenicity, and potentially drug responsiveness⁶. Although widespread alternative splicing has been suggested in schistosomiasis, it remains poorly characterized⁷. Previous short-read transcriptomic studies have revealed stage- and sex-specific gene expression patterns related to host adaptation and development^3,8,9, but such approaches lack the resolution to accurately capture alternative splicing events that may drive phenotypic diversity, and even drug resistance, such as TRPM channels, other receptor families, and PZQ resistance-associated isoforms¹⁰, offering both new drug targets and diagnostic biomarkers. To address this limitation, we aim to apply Oxford Nanopore Technologies (ONT) long-read sequencing to profile full-length transcripts across key life-cycle stages of Schistosoma mansoni. This approach enables comprehensive isoform identification, improved transcriptome annotation, and precise mapping of alternative splicing events. By defining stage-specific gene isoforms, we seek to establish a lifecycle-resolved molecular “fingerprint” of schistosome infection, supporting the discovery of novel diagnostic markers and therapeutic targets while expanding the application of long-read transcriptomics in schistosomiasis research.

Methodology Parasite material was obtained from the established Schistosoma mansoni (NMRI strain) life cycle, including cercariae, miracidia, eggs, schistosomula, and adult worms, maintained at TUM (Prof. C. Prazeres da Costa). Total RNA was extracted and quality assessed (RIN) prior to preparation of Oxford Nanopore Technologies (ONT) full-length cDNA libraries, as per guidance from Dr. Arne Jacobs. The ONT transcriptomic data will be analyzed to profile Schistosoma parasites across key life-cycle stages to define alternative splicing events, under the expert guidance of Dr. Jacobs as well. Raw ONT reads will be filtered for quality and aligned to the