DUET-seq: An Open-Source Droplet Platform for High-Fidelity Joint Chromatin and Transcriptome Profiling Reveals Temporal Regulatory Decoupling in Single Cells

By providing a fully disclosed reagent-and-device ecosystem, DUET-seq enables researchers to optimize lysis and reaction chemistry for non-standard tissues without proprietary constraints. We demonstrate the platform’s versatility by mapping over 14,000 cis-regulatory element-to-gene linkages in adult mouse brain and by profiling ~29,000 nuclei across six stages of postnatal spermatogenesis, where paired measurements reveal two modes of temporal regulatory decoupling—epigenetic priming and chromatin inertia—that are inaccessible to unimodal assays.

DUET-seq thus provides an accessible, cost-effective framework for joint single-nucleus multi-omic profiling, with broad applicability across developmental biology, disease epigenomics, and functional genomics.