{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T06:22:58Z","timestamp":1773469378435,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union, ERC StG, MULTIview-CELL","award":["101115618"],"award-info":[{"award-number":["101115618"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Chromatin 3D folding creates numerous DNA interactions, participating in gene expression regulation. Single-cell chromatin-accessibility assays now profile hundreds of thousands of cells, challenging existing methods for mapping cis-regulatory interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We present CIRCE, a fast and scalable Python package to predict cis-regulatory DNA interactions from single-cell chromatin accessibility data. CIRCE re-implements the Cicero workflow to analyse single-cell atlases, cutting runtime and memory use by several orders of magnitude. We also provide new options to compute metacells, grouping similar cells to reduce data sparsity. We benchmarked CIRCE against Cicero on two datasets of different sizes and demonstrated the improvement from CIRCE\u2019s metacells\u2019 strategy with promoter capture Hi-C data. We also evaluated how DNA interaction predictions are impacted by different pre-processing. We observed a negative impact of Cicero\u2019s count normalization, and the best performance was obtained with the single-cell count matrix directly. Finally, we demonstrated the scalability of CIRCE by processing a dataset of more than 700\u2009000 cells and 1 million DNA regions in less than an hour. CIRCE should greatly facilitate the prediction of DNA region interactions for scverse and Python users, while providing new and up-to-date pre-processing insights.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>CIRCE is released as an open-source software under the AGPL-3.0 licence. The package source code is available on GitHub at https:\/\/github.com\/cantinilab\/CIRCE, and its documentation is accessible at https:\/\/circe.readthedocs.io. The code to reproduce the presented results is available as a Snakemake pipeline at https:\/\/github.com\/cantinilab\/circe_reproducibility.s.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag092","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T12:39:33Z","timestamp":1771591173000},"source":"Crossref","is-referenced-by-count":0,"title":["CIRCE: a scalable Python package to predict cis-regulatory DNA interactions from single-cell chromatin accessibility data"],"prefix":"10.1093","volume":"42","author":[{"given":"R\u00e9mi","family":"Trimbour","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR 3738, Machine Learning for Integrative Genomics Group , Paris F-75015,","place":["France"]}]},{"given":"Julio","family":"Saez-Rodriguez","sequence":"additional","affiliation":[{"name":"Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for 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