{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T01:03:23Z","timestamp":1775264603087,"version":"3.50.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center For Advancing Translational Science","doi-asserted-by":"crossref","award":["5KL2TR002492"],"award-info":[{"award-number":["5KL2TR002492"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute Of General Medical Sciences","doi-asserted-by":"crossref","award":["1R35GM142695"],"award-info":[{"award-number":["1R35GM142695"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["U01 HL089897"],"award-info":[{"award-number":["U01 HL089897"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["U01 HL089856"],"award-info":[{"award-number":["U01 HL089856"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Epidemiologic and genetic studies in many complex diseases suggest subgroup disparities (e.g. by sex, race) in disease course and patient outcomes. We consider this from the standpoint of integrative analysis where we combine information from different views (e.g. genomics, proteomics, clinical data). Existing integrative analysis methods ignore the heterogeneity in subgroups, and stacking the views and accounting for subgroup heterogeneity does not model the association among the views. We propose Heterogeneity in Integration and Prediction (HIP), a statistical approach for joint association and prediction that leverages the strengths in each view to identify molecular signatures that are shared by and specific to a subgroup. We apply HIP to proteomics and gene expression data pertaining to chronic obstructive pulmonary disease (COPD) to identify proteins and genes shared by, and unique to, males and females, contributing to the variation in COPD, measured by airway wall thickness. Our COPD findings have identified proteins, genes, and pathways that are common across and specific to males and females, some implicated in COPD, while others could lead to new insights into sex differences in COPD mechanisms. HIP accounts for subgroup heterogeneity in multi-view data, ranks variables based on importance, is applicable to univariate or multivariate continuous outcomes, and incorporates covariate adjustment. With the efficient algorithms implemented using PyTorch, this method has many potential scientific applications and could enhance multiomics research in health disparities. HIP is available at https:\/\/github.com\/lasandrall\/HIP, a video tutorial at https:\/\/youtu.be\/O6E2OLmeMDo and a Shiny Application at https:\/\/multi-viewlearn.shinyapps.io\/HIP_ShinyApp\/ for users with limited programming experience.<\/jats:p>","DOI":"10.1093\/bib\/bbae470","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T08:48:07Z","timestamp":1727686087000},"source":"Crossref","is-referenced-by-count":4,"title":["HIP: a method for high-dimensional multi-view data integration and prediction accounting for subgroup heterogeneity"],"prefix":"10.1093","volume":"25","author":[{"given":"Jessica","family":"Butts","sequence":"first","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota , Minneapolis, MN 55414,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif","family":"Verace","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota , Minneapolis, MN 55414,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Wendt","sequence":"additional","affiliation":[{"name":"Division of Pulmonary , Allergy and Critical Care, , Minneapolis, MN 55455,","place":["USA"]},{"name":"University of Minnesota , Allergy and Critical Care, , Minneapolis, MN 55455,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russel P","family":"Bowler","sequence":"additional","affiliation":[{"name":"Division of Pulmonary , Critical Care and Sleep Medicine, Department of Medicine, , Denver, CO 80206,","place":["USA"]},{"name":"National Jewish Health , Critical Care and Sleep Medicine, Department of Medicine, , Denver, CO 80206,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig P","family":"Hersh","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine , Brigham and Women\u2019s Hospital, , Boston, MA 02115,","place":["USA"]},{"name":"Harvard Medical School , Brigham and Women\u2019s Hospital, , Boston, MA 02115,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Biostatistics , Epidemiology and Informatics, Perelman School of Medicine, , Philadelphia, PA 19104,","place":["USA"]},{"name":"University of Pennsylvania , Epidemiology and Informatics, Perelman School of Medicine, , Philadelphia, PA 19104,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Eberly","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota , Minneapolis, MN 55414,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra E","family":"Safo","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota , Minneapolis, MN 55414,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,9,29]]},"reference":[{"key":"2024093008475187800_ref1","first-page":"289","article-title":"Employment and activity limitations among adults with chronic obstructive pulmonary disease\u2014United States, 2013","volume":"64","author":"Wheaton","year":"2015","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2024093008475187800_ref2"},{"key":"2024093008475187800_ref3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.15326\/jcopdf.1.1.2014.0120","article-title":"Chronic obstructive pulmonary disease genetics: a review of the past and a look into the future","volume":"1","author":"Hardin","year":"2014","journal-title":"Chronic Obstr Pulm Dis"},{"key":"2024093008475187800_ref4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1378\/chest.08-2114","article-title":"Risk of copd from exposure to biomass smoke: a metaanalysis","volume":"138","author":"Hu","year":"2010","journal-title":"Chest"},{"key":"2024093008475187800_ref5","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1164\/ajrccm.163.5.2101039","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: Nhlbi\/who global initiative for chronic obstructive lung disease (gold) workshop summary","volume":"163","author":"Pauwels","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"2024093008475187800_ref6","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1183\/09031936.00018908","article-title":"Multifaceted mechanisms in copd: Inflammation, immunity, and tissue repair and destruction","volume":"31","author":"Chung","year":"2008","journal-title":"Eur Respir J"},{"key":"2024093008475187800_ref7","doi-asserted-by":"publisher","first-page":"32","DOI":"10.3109\/15412550903499522","article-title":"Genetic epidemiology of copd (copdgene) study design","volume":"7","author":"Regan","year":"2011","journal-title":"COPD: J Chron Obstruct Pulmon Dis"},{"key":"2024093008475187800_ref8","first-page":"813","article-title":"Sex differences in chronic obstructive pulmonary disease mechanisms","volume-title":"Am J Respir Crit Care Med","author":"Barnes","year":"2016"},{"key":"2024093008475187800_ref9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1465-9921-7-52","article-title":"Female smokers beyond the perimenopausal period are at increased risk of chronic obstructive pulmonary disease: a systematic review and meta-analysis","volume":"7","author":"Gan","year":"2006","journal-title":"Respir Res"},{"key":"2024093008475187800_ref10","doi-asserted-by":"publisher","first-page":"285","DOI":"10.3109\/15412555.2011.586658","article-title":"Gender differences of airway dimensions in anatomically matched sites on ct in smokers","volume":"8","author":"Kim","year":"2011","journal-title":"COPD: J Chron Obstruct Pulmon Dis"},{"key":"2024093008475187800_ref11","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1183\/09031936.97.10040822","article-title":"Gender difference in smoking effects on lung function and risk of hospitalization for copd: results from a danish longitudinal population study","volume":"10","author":"Prescott","year":"1997","journal-title":"Eur Respir J"},{"key":"2024093008475187800_ref12","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1111\/biom.13458","article-title":"Sparse linear discriminant analysis for multiview structured data","volume":"78","author":"Safo","year":"2021","journal-title":"Biometrics"},{"key":"2024093008475187800_ref13","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1093\/biostatistics\/kxab016","article-title":"Bayesian integrative analysis and prediction with application to atherosclerosis cardiovascular disease","volume-title":"Biostatistics","author":"Chekouo","year":"2020"},{"key":"2024093008475187800_ref14","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1093\/biostatistics\/kxw001","article-title":"Canonical variate regression","volume":"17","author":"Luo","year":"2016","journal-title":"Biostatistics"},{"key":"2024093008475187800_ref15","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/biostatistics\/kxy035","article-title":"The joint lasso: high-dimensional regression for group structured data","volume":"21","author":"Dondelinger","year":"2018","journal-title":"Biostatistics"},{"key":"2024093008475187800_ref16","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1111\/biom.12213","article-title":"Meta-analysis based variable selection for gene expression data","volume":"70","author":"Li","year":"2014","journal-title":"Biometrics"},{"key":"2024093008475187800_ref17","first-page":"8024","article-title":"Pytorch: an imperative style, high-performance deep learning library","volume-title":"Advances in Neural Information Processing Systems 32","author":"Paszke","year":"2019"},{"key":"2024093008475187800_ref18","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780198510581.001.0001","volume-title":"Procrustes Problems","author":"Gower","year":"2004"},{"key":"2024093008475187800_ref19","volume-title":"CVR: Canonical Variate Regression","author":"Luo","year":"2017"},{"key":"2024093008475187800_ref20","volume-title":"Fuser: Fused Lasso for High-Dimensional Regression over Groups","author":"Dondelinger","year":"2018"},{"key":"2024093008475187800_ref21","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1111\/j.2517-6161.1996.tb02080.x","article-title":"Regression shrinkage and selection via the lasso","volume":"58","author":"Tibshirani","year":"1994","journal-title":"J R Stat Soc Ser B"},{"key":"2024093008475187800_ref22","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/j.1467-9868.2005.00503.x","article-title":"Regularization and variable selection via the elastic net","volume":"67","author":"Zou","year":"2005","journal-title":"Journal of the Royal Statistical Society, Series B"},{"key":"2024093008475187800_ref23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization paths for generalized linear models via coordinate descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J Stat Softw"},{"key":"2024093008475187800_ref24","doi-asserted-by":"publisher","first-page":"3886","DOI":"10.1093\/nar\/gkv256","article-title":"Submirine: Assessing variants in microrna targets using clinical genomic data sets","volume":"43","author":"Maxwell","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2024093008475187800_ref25","doi-asserted-by":"publisher","first-page":"14","DOI":"10.4103\/ijabmr.IJABMR_65_17","article-title":"Association of adiponectin with lung function impairment and disease severity in chronic obstructive pulmonary disease","volume":"8","author":"Jaswal","year":"2018","journal-title":"Int J Appl Basic Med Res"},{"key":"2024093008475187800_ref26","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal analysis approaches in ingenuity pathway analysis","volume":"30","author":"Kramer","year":"2014","journal-title":"Bionformatics"},{"key":"2024093008475187800_ref27","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3390\/ph12010005","article-title":"Iron homeostasis in the lungs\u2014a balance between health and disease","volume":"12","author":"Neves","year":"2019","journal-title":"Pharmaceuticals"},{"key":"2024093008475187800_ref28","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1164\/rccm.201702-0311PP","article-title":"The \u201diron\u201d-y of iron overload and iron deficiency in chronic obstructive pulmonary disease","volume":"196","author":"Cloonan","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2024093008475187800_ref29","first-page":"A7096","article-title":"Small airway epithelial responses associated with enhanced female susceptibility to smoking-related lung disease","volume":"199","author":"Salit","year":"2019","journal-title":"American Thoracic Society"},{"key":"2024093008475187800_ref30","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.2147\/JIR.S337894","article-title":"Peripheral blood mononuclear cell gene expression in chronic obstructive pulmonary disease: Mirna and mrna regulation","volume":"15","author":"Wang","year":"2022","journal-title":"J Inflamm Res"},{"key":"2024093008475187800_ref31","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.00569-2021","article-title":"\u201dAn interferon-inducible signature of airway disease from blood gene expression profiling","volume":"59","author":"Yun","year":"2022","journal-title":"Eur Respir J"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/6\/bbae470\/59428507\/bbae470.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/6\/bbae470\/59428507\/bbae470.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T08:48:13Z","timestamp":1727686093000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbae470\/7790998"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,23]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,9,23]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbae470","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,11]]},"published":{"date-parts":[[2024,9,23]]},"article-number":"bbae470"}}