{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T16:11:27Z","timestamp":1762445487053,"version":"3.41.2"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Agence Nationale pour la Recherche","award":["ANR-20-CE15-0012-01"],"award-info":[{"award-number":["ANR-20-CE15-0012-01"]}]},{"name":"INCEPTION program","award":["ANR-16-CONV-0005"],"award-info":[{"award-number":["ANR-16-CONV-0005"]}]},{"name":"Agence Nationale pour la Recherche","award":["ANR-10-LABX-69-01"],"award-info":[{"award-number":["ANR-10-LABX-69-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Multivariate analysis is becoming central in studies investigating high-throughput molecular data, yet, some important features of these data are seldom explored. Here, we present MANOCCA (Multivariate Analysis of Conditional CovAriance), a powerful method to test for the effect of a predictor on the covariance matrix of a multivariate outcome. The proposed test is by construction orthogonal to tests based on the mean and variance and is able to capture effects that are missed by both approaches. We first compare the performances of MANOCCA with existing correlation-based methods and show that MANOCCA is the only test correctly calibrated in simulation mimicking omics data. We then investigate the impact of reducing the dimensionality of the data using principal component analysis when the sample size is smaller than the number of pairwise covariance terms analysed. We show that, in many realistic scenarios, the maximum power can be achieved with a limited number of components. Finally, we apply MANOCCA to 1000 healthy individuals from the Milieu Interieur cohort, to assess the effect of health, lifestyle and genetic factors on the covariance of two sets of phenotypes, blood biomarkers and flow cytometry\u2013based immune phenotypes. Our analyses identify significant associations between multiple factors and the covariance of both omics data.<\/jats:p>","DOI":"10.1093\/bib\/bbae272","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T12:08:52Z","timestamp":1718021332000},"source":"Crossref","is-referenced-by-count":1,"title":["MANOCCA: a robust and computationally efficient test of covariance in high-dimension multivariate omics data"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5479-3550","authenticated-orcid":false,"given":"Christophe","family":"Boetto","sequence":"first","affiliation":[{"name":"Department of Computational Biology, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9 , 25-28 rue du Dr Roux, 75015 Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur","family":"Frouin","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9 , 25-28 rue du Dr Roux, 75015 Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e9o","family":"Henches","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9 , 25-28 rue du Dr Roux, 75015 Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Auvergne","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9 , 25-28 rue du Dr Roux, 75015 Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9 , 25-28 rue du Dr Roux, 75015 Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etienne","family":"Patin","sequence":"additional","affiliation":[{"name":"Human Evolutionary Genetics Unit, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9 , CNRS UMR2000, 25-28 rue Dr Roux, 75015 Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius","family":"Bredon","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9 , INSERM, Centre de recherche Saint-Antoine, CRSA, Microbiota, Gut and Inflammation Laboratory, , 27 rue Chaligny, 75012 Paris , France"},{"name":"H\u00f4pital Saint-Antoine (UMR S938) Sorbonne Universit\u00e9 , INSERM, Centre de recherche Saint-Antoine, CRSA, Microbiota, Gut and Inflammation Laboratory, , 27 rue Chaligny, 75012 Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alec","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University California Los Angeles , 695 Charles E. Young Drive South, Box 708822, Los Angeles, CA 90095-7088 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milieu Interieur","family":"Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sriram","family":"Sankararaman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University California Los Angeles , 695 Charles E. Young Drive South, Box 708822, Los Angeles, CA 90095-7088 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noah","family":"Zaitlen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University California Los Angeles , 695 Charles E. Young Drive South, Box 708822, Los Angeles, CA 90095-7088 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean P","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9 , 25-28 rue du Dr Roux, 75015 Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lluis","family":"Quintana-Murci","sequence":"additional","affiliation":[{"name":"Human Evolutionary Genetics Unit, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9 , CNRS UMR2000, 25-28 rue Dr Roux, 75015 Paris , France"},{"name":"Chair of Human Genomics and Evolution , Coll\u00e8ge de France, 11 Pl. Marcelin Berthelot, 75005 Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darragh","family":"Duffy","sequence":"additional","affiliation":[{"name":"Translational Immunology Unit, Institut Pasteur, Universit\u00e9 de Paris Cit\u00e9 , 25-28 rue du Dr Roux, 75015 Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry","family":"Sokol","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9 , INSERM, Centre de recherche Saint-Antoine, CRSA, Microbiota, Gut and Inflammation Laboratory, , 27 rue Chaligny, 75012 Paris , France"},{"name":"H\u00f4pital Saint-Antoine (UMR S938) Sorbonne Universit\u00e9 , INSERM, Centre de recherche Saint-Antoine, CRSA, Microbiota, Gut and Inflammation Laboratory, , 27 rue Chaligny, 75012 Paris , France"},{"name":"Paris Center for Microbiome Medicine, F\u00e9d\u00e9ration Hospitalo-Universitaire , 184 rue du Faubourg Saint-Antoine, 75571 PARIS Cedex 12 , 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