{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T23:09:38Z","timestamp":1768691378096,"version":"3.49.0"},"reference-count":6,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Center for Individualized Medicine at Mayo Clinic (J.C.), National Science Foundation","award":["DMS-1830392"],"award-info":[{"award-number":["DMS-1830392"]}]},{"name":"Center for Individualized Medicine at Mayo Clinic (J.C.), National Science Foundation","award":["DMS-1811747"],"award-info":[{"award-number":["DMS-1811747"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 HG011662"],"award-info":[{"award-number":["R21 HG011662"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Summary<\/jats:title>\n                  <jats:p>PERMANOVA (permutational multivariate analysis of variance based on distances) has been widely used for testing the association between the microbiome and a covariate of interest. Statistical significance is established by permutation, which is computationally intensive for large sample sizes. As large-scale microbiome studies, such as American Gut Project (AGP), become increasingly popular, a computationally efficient version of PERMANOVA is much needed. To achieve this end, we derive the asymptotic distribution of the PERMANOVA pseudo-F statistic and provide analytical P-value calculation based on chi-square approximation. We show that the asymptotic P-value is close to the PERMANOVA P-value even under a moderate sample size. Moreover, it is more accurate and an order-of-magnitude faster than the permutation-free method MDMR. We demonstrated the use of our procedure D-MANOVA on the AGP dataset.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>D-MANOVA is implemented by the dmanova function in the CRAN package GUniFrac.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab498","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T11:20:44Z","timestamp":1625656844000},"page":"286-288","source":"Crossref","is-referenced-by-count":20,"title":["D-MANOVA: fast distance-based multivariate analysis of variance for large-scale microbiome association studies"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1273-5624","authenticated-orcid":false,"given":"Jun","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Statistics, Texas A&M University , College Station, TX 77840, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"2023020108384666800_btab498-B1","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1093\/bioinformatics\/bts342","article-title":"Associating microbiome composition with environmental covariates using generalized UniFrac distances","volume":"28","author":"Chen","year":"2012","journal-title":"Bioinformatics"},{"key":"2023020108384666800_btab498-B2","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/j.mayocp.2017.10.004","article-title":"Microbiome at the frontier of personalized medicine","volume":"92","author":"Kashyap","year":"2017","journal-title":"Mayo Clin. 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