{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T02:04:46Z","timestamp":1778637886050,"version":"3.51.4"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01EY029548"],"award-info":[{"award-number":["5R01EY029548"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5P30EY001765"],"award-info":[{"award-number":["5P30EY001765"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Intercellular communication (i.e. cell\u2013cell communication) plays an essential role in multicellular organisms coordinating various biological processes. Previous studies discovered that feedback loops between two cell types are a widespread and vital signaling motif regulating development, regeneration and cancer progression. While many computational methods have been developed to predict cell\u2013cell communication based on gene expression datasets, these methods often predict one-directional ligand\u2013receptor interactions from sender to receiver cells and are not suitable to identify feedback loops.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we describe ligand\u2013receptor loop (LRLoop), a new method for analyzing cell\u2013cell communication based on bi-directional ligand\u2013receptor interactions, where two pairs of ligand\u2013receptor interactions are identified that are responsive to each other and thereby form a closed feedback loop. We first assessed LRLoop using bulk datasets and found our method significantly reduces the false positive rate seen with existing methods. Furthermore, we developed a new strategy to assess the performance of these methods in single-cell datasets. We used the between-tissue interactions as an indicator of potential false-positive prediction and found that LRLoop produced a lower fraction of between-tissue interactions than traditional methods. Finally, we applied LRLoop to the single-cell datasets obtained from retinal development. We discovered many new bi-directional ligand\u2013receptor interactions among individual cell types that potentially control proliferation, neurogenesis and\/or cell fate specification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>An R package is available at https:\/\/github.com\/Pinlyu3\/LRLoop. The source code can be found at figshare (https:\/\/doi.org\/10.6084\/m9.figshare.20126138.v1). The datasets can be found at figshare (https:\/\/doi.org\/10.6084\/m9.figshare.20126021.v1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac447","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T13:47:18Z","timestamp":1657028838000},"page":"4117-4126","source":"Crossref","is-referenced-by-count":35,"title":["LRLoop: a method to predict feedback loops in cell\u2013cell communication"],"prefix":"10.1093","volume":"38","author":[{"given":"Ying","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Johns Hopkins University School of Medicine , Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pin","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Johns Hopkins University School of Medicine , Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyao","family":"Jiang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou 510530, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1525-9969","authenticated-orcid":false,"given":"Fengquan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Johns Hopkins University School of Medicine , Baltimore, MD 21287, USA"},{"name":"Solomon H. 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