{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:41:38Z","timestamp":1773902498082,"version":"3.50.1"},"reference-count":11,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["1R01CA291963-01"],"award-info":[{"award-number":["1R01CA291963-01"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>The genome interacts with itself within the volume of the cell nucleus to process information. These interactions mediate signal integration, gene regulation, and cell identity. The identification of new therapeutic targets from non-coding disease-associated variants relies critically on correctly assigning variants to genes through 3D interactions. Experimental techniques in 3D genomics, such as HiC and HiChIP, allow the mapping of interactions through sequencing. Bioinformatics for 3D genomics contends primarily with contact matrices that contain interaction frequencies for all possible element pairs, and BEDPE files that store element pairs that interact. Whereas the tools available for processing linear genomic data are mature, operating on contact matrices and BEDPE files remains cumbersome, opaque, and error-prone, as researchers have had to shoehorn tools originally designed for linear data. A genome arithmetic designed from the ground up for 3D genomics does not yet exist.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We present AQuA Tools, a suite of shell- and R-based command-line tools that provide a set of core operations on contact matrices and BEDPE files motivated by key questions in population genetics, cancer research, and precision medicine. We have designed our core operations to be clear, reliable, intuitive and versatile. Core operations can be chained together along with standard UNIX commands. Our goal is to make AQuA Tools easy for the novice to learn and the go-to choice for power users. We hope our tools will motivate more researchers to use 3D genomic data in their projects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>We provide and maintain AQuA Tools at https:\/\/github.com\/axiotl\/aqua-tools.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf510","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T23:17:30Z","timestamp":1758323850000},"source":"Crossref","is-referenced-by-count":2,"title":["AQuA Tools: clear and reliable BEDPE operations for 3D genomics"],"prefix":"10.1093","volume":"41","author":[{"given":"Maharshi","family":"Chakraborty","sequence":"first","affiliation":[{"name":"Axiotl Inc. , Cleveland, OH 44106,","place":["United States"]}]},{"given":"Laura","family":"Morgan","sequence":"additional","affiliation":[{"name":"Axiotl Inc. , Cleveland, OH 44106,","place":["United States"]}]},{"given":"Quin","family":"Scacheri","sequence":"additional","affiliation":[{"name":"Axiotl Inc. , Cleveland, OH 44106,","place":["United States"]}]},{"given":"Alexandra","family":"D\u2019Yan","sequence":"additional","affiliation":[{"name":"Axiotl Inc. , Cleveland, OH 44106,","place":["United States"]}]},{"given":"Hyunmin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, Case Western Reserve University , Cleveland, OH, 44106,","place":["United States"]}]},{"given":"Yaw","family":"Asante","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, Case Western Reserve University , Cleveland, OH, 44106,","place":["United States"]}]},{"given":"Diana","family":"Chin","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, Case Western Reserve University , Cleveland, OH, 44106,","place":["United States"]}]},{"given":"Olivia","family":"Corradin","sequence":"additional","affiliation":[{"name":"Whitehead Institute of Biomedical Research , Cambridge, MA 02142,","place":["United States"]},{"name":"Massachusetts Institute of Technology , Cambridge, MA 02139,","place":["United States"]}]},{"given":"Peter","family":"Scacheri","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, Case Western Reserve University , Cleveland, OH, 44106,","place":["United States"]}]},{"given":"Richard","family":"Sallari","sequence":"additional","affiliation":[{"name":"Axiotl Inc. , Cleveland, OH 44106,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0130-2302","authenticated-orcid":false,"given":"Berkley","family":"Gryder","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, Case Western Reserve University , Cleveland, OH, 44106,","place":["United States"]}]}],"member":"286","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"2025092219523239700_btaf510-B1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cels.2016.07.002","article-title":"Juicer provides a one-click system for analyzing loop-resolution Hi-C experiments","volume":"3","author":"Durand","year":"2016","journal-title":"Cell Syst"},{"key":"2025092219523239700_btaf510-B2","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41587-020-0439-x","article-title":"The Nf-core framework for community-curated bioinformatics pipelines","volume":"38","author":"Ewels","year":"2020","journal-title":"Nat Biotechnol"},{"key":"2025092219523239700_btaf510-B3","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/s41596-019-0285-9","article-title":"Measurement of differential chromatin interactions with absolute quantification of architecture (AQuA-HiChIP)","volume":"15","author":"Gryder","year":"2020","journal-title":"Nat Protoc"},{"key":"2025092219523239700_btaf510-B0272985","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1186\/s13059-020-02215-9","article-title":"FAN-C: A feature-rich framework for the analysis and visualisation of chromosome conformation capture data","volume":"21","author":"Kruse","year":"2020","journal-title":"Genome Biol"},{"key":"2025092219523239700_btaf510-B4","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/nmeth.3999","article-title":"HiChIP: efficient and sensitive analysis of protein-directed genome architecture","volume":"13","author":"Mumbach","year":"2016","journal-title":"Nat Methods"},{"key":"2025092219523239700_btaf510-B5","doi-asserted-by":"crossref","first-page":"e1012164","DOI":"10.1371\/journal.pcbi.1012164","article-title":"Pairtools: from sequencing data to chromosome contacts","volume":"20","author":"Open2C","year":"2024","journal-title":"PLoS Comput Biol"},{"key":"2025092219523239700_btaf510-B6","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"2025092219523239700_btaf510-B7","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/j.cell.2014.11.021","article-title":"A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping","volume":"159","author":"Rao","year":"2014","journal-title":"Cell"},{"key":"2025092219523239700_btaf510-B8","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.cels.2018.01.001","article-title":"Juicebox.Js provides a cloud-based visualization system for Hi-C data","volume":"6","author":"Robinson","year":"2018","journal-title":"Cell Syst"},{"key":"2025092219523239700_btaf510-B9","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/s13059-015-0831-x","article-title":"HiC-Pro: an optimized and flexible pipeline for Hi-C data processing","volume":"16","author":"Servant","year":"2015","journal-title":"Genome Biol"},{"key":"2025092219523239700_btaf510-B3010748","doi-asserted-by":"publisher","first-page":"W177","DOI":"10.1093\/nar\/gkaa220","article-title":"Galaxy hicexplorer 3: A web server for reproducible hi-C, capture hi-C AND single-cell hi-C data analysis, quality control and visualization","volume":"48","author":"Wolff","year":"2020","journal-title":"Nucleic Acids Res"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaf510\/64302268\/btaf510.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/9\/btaf510\/64302268\/btaf510.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/9\/btaf510\/64302268\/btaf510.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T23:52:37Z","timestamp":1758585157000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btaf510\/8256682"}},"subtitle":[],"editor":[{"given":"Peter","family":"Robinson","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":11,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaf510","relation":{},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,9]]},"published":{"date-parts":[[2025,9,1]]},"article-number":"btaf510"}}