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. 2024 Oct 23;634(8036):1211–1220. doi: 10.1038/s41586-024-08070-z

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 3 — (a) Sequences nominated by DHS accessibility (DHS-natural) and by Malinois (Malinois-natural) were intersected with ENCODE cCREs (promoter-like sequences, proximal enhancer-like sequences, distal enhancer-like sequences, and CTCF-only) to determine overlap with existing putative regulatory elements. 94% of DHS-natural sequences intersect a cCRE while only 34.2% of Malinois-natural sequences intersect a cCRE suggesting that Malinois may exploit sequences features not captured by typical cCRE measures to select a sequence that drives cell type-specific activity. (b) To explore additional genomic features that may overlap DHS-natural and Malinois-natural sequences were annotated using annotatePeaks.pl from the HOMER suite. Annotations were generated for the whole genome (hg38), the DHS-natural and Malinois-natural libraries as a whole, as well as DHS-natural and Malinois-natural by individual cell type. DHS-natural and Malinois-natural largely resemble the distribution of annotations genome-wide barring an overrepresentation of simple repeats in Malinois-natural sequences driven by SK-N-SH sequences. Despite this, selected sequences seem to be a representative sample of genomic features. (c) DHS-natural and Malinois-natural sequences were intersected to determine overlap between naturally occurring sequences. Notably overlap was minimal between selection methods (0.10%-4.1%) depending on cell type.