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Increasing usable reads in RNA-seq protocols.

Created on 09 Aug 2026

Authors

Felix Pförtner, Eva Briem, Wolfgang Enard, Daniel Richter

Published in

iScience. Volume 29. Issue 8. Pages 116984. Aug 21, 2026. Epub Jul 30, 2026.

Abstract

Bulk and single-cell RNA-seq are powerful tools for transcriptomic analysis, providing insights into molecular and cellular phenotypes. Costs constrain the biological insights obtainable within a given budget, and as sequencing prices decline, efficient library protocols have become a decisive factor. In this study, we introduce an approach to systematically optimize the number of usable reads generated by RNA-seq protocols. We applied this "funnel strategy" to prime-seq, an early-barcoding bulk RNA-seq protocol, by systematically testing critical protocol steps totaling 1,256 samples in 65 libraries. This resulted in the optimized prime-seq2 protocol that increases the number of usable reads by 60% and improves one of the most cost-efficient bulk RNA-seq protocols available. Our study also suggests that monitoring usable reads can serve as a valuable quality control for many RNA-seq protocols and sheds light on the complex interplay of experimental conditions that shape RNA-seq library composition and their interpretation.

PMID:
42571425
Bibliographic data and abstract were imported from PubMed on 09 Aug 2026.

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