381: Light-written spatial barcodes enable tunable multiomic sequencing (BALI)

Battistoni G et al., PNAS - This paper presents BALI, a light-driven method that writes combinatorial DNA spatial barcodes directly onto biomolecules in tissue by iterative photocleavage and ligation, enabling user-defined, scalable spatial profiling of RNA, chromatin accessibility, or both from the same section and automation via a LightScribe instrument. Key terms: spatial multiomics, photocaged ligation, BALI, LightScribe, chromatin accessibility. Study Highlights:BALI uses a photocaged ligation root and patterned UV illumination to direct iterative DNA ligations that assemble combinatorial spatial barcodes in situ. The method achieves tunable spatial resolution down to ~3 µm and can scale barcode complexity from a few regions to theoretical millions by increasing barcode digits. As proof of concept, the authors profiled transcriptomes and chromatin accessibility in defined regions of embryonic and adult mouse brain and combined both readouts in a single-section multiomic workflow, showing concordance with established datasets. They also built the LightScribe instrument to automate combinatorial barcode writing and demonstrated automated encoding of hundreds of regions. Conclusion:BALI couples light-directed combinatorial ligation with standard sequencing workflows to offer histology-aware, tunable, and scalable spatial multiomic profiling with subcellular resolution and an accessible automation path, enabling targeted high-throughput studies across large sample sets. Music:Enjoy the music based on this article at the end of the episode. Article title:Spatially tuneable multiomic sequencing using light-driven combinatorial barcoding of molecules in tissues First author:Battistoni G Journal:PNAS DOI:10.1073/pnas.2527896123 Reference:Battistoni G, Torres-Garcia S, Sia CY, Corriero S, Boquetale C, Williams E, et al. Spatially tuneable multi-omics sequencing using light-driven combinatorial barcoding of molecules in tissues. Proc Natl Acad Sci U S A. 2026;123(21):e2527896123. doi:10.1073/pnas.2527896123 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/bali-light-driven-combinatorial-barcoding QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-06-01. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited the transcript sections describing the BALI method, UV uncaging, iterative ligation, LightScribe automation, and multiomic validation (RNA and ATAC) as well as scalability and cost considerations; compared these claims with the canonical article.- transcript topics: Spatial omics trade-offs and the need for histology-driven boundaries; BALI: Barcoding by Activated Linkage of Indexes; UV uncaging, ligation cycles, and barcode encoding; LightScribe automation with DMD mirrors; RNA profiling in embryonic mouse brain regions; Chromatin accessibility (ATAC) profiling in brain tissue QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 5- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:-...