{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T23:07:52Z","timestamp":1781478472081,"version":"3.54.1"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000183","name":"Army Research Office","doi-asserted-by":"publisher","award":["W911NF-11-1-0429"],"award-info":[{"award-number":["W911NF-11-1-0429"]}],"id":[{"id":"10.13039\/100000183","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI-1053486"],"award-info":[{"award-number":["DBI-1053486"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54DE023798"],"award-info":[{"award-number":["U54DE023798"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Modern biological screens yield enormous numbers of measurements, and identifying and interpreting statistically significant associations among features are essential. In experiments featuring multiple high-dimensional datasets collected from the same set of samples, it is useful to identify groups of associated features between the datasets in a way that provides high statistical power and false discovery rate (FDR) control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we present a novel hierarchical framework, HAllA (Hierarchical All-against-All association testing), for structured association discovery between paired high-dimensional datasets. HAllA efficiently integrates hierarchical hypothesis testing with FDR correction to reveal significant linear and non-linear block-wise relationships among continuous and\/or categorical data. We optimized and evaluated HAllA using heterogeneous synthetic datasets of known association structure, where HAllA outperformed all-against-all and other block-testing approaches across a range of common similarity measures. We then applied HAllA to a series of real-world multiomics datasets, revealing new associations between gene expression and host immune activity, the microbiome and host transcriptome, metabolomic profiling and human health phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>An open-source implementation of HAllA is freely available at http:\/\/huttenhower.sph.harvard.edu\/halla along with documentation, demo datasets and a user group.<\/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\/btac232","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T19:28:32Z","timestamp":1651001312000},"page":"i378-i385","source":"Crossref","is-referenced-by-count":71,"title":["High-sensitivity pattern discovery in large, paired multiomic datasets"],"prefix":"10.1093","volume":"38","author":[{"given":"Andrew R","family":"Ghazi","sequence":"first","affiliation":[{"name":"Biostatistics Department, Harvard T. 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