The combination of spatial transcriptomics with long-read sequencing enables spatial characterization of full-length transcripts within solid tissue sections. However, standardized computational analysis frameworks are lacking, and it remains unclear whether available long-read sequencing platforms from Oxford Nanopore Technologies and Pacific Biosciences yield comparable results. Here, we present a computational strategy for spatial full-length transcript analysis, focusing on the spatial profiling of adaptive immune receptor repertoires (AIRR). Our approach introduces an adaptive filtering strategy that dynamically refines read selection and significantly improves consensus accuracy, enabling high-confidence sequence reconstruction independent of platform-specific sequencing error profiles. We further derive evidence-based guidelines tailored to the consistent and robust analysis of spatial AIRR data. The resulting software LongAIRR is modular and interoperable with existing spatial transcriptomics and AIRR analysis frameworks. This work establishes a methodological foundation for spatial immunology, enabling precise mapping of immune repertoires within their native tissue microenvironments.
Schuck, J., Ortega Iannazzo, S., Mahmoud, Z., Gwellem Anchang, C., Hasse, L. M., Weber, K., Imkeller, K.
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