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However, previous studies have typically labeled each specimen as either healthy or with a specific disease, ignoring prevalence of complications or comorbidities in actual cohorts, which may confound the microbial\u2013disease associations. For instance, a patient may suffer from multiple diseases, making it challenging to detect their health status accurately. Furthermore, host phenotypes like physiological characteristics and lifestyles can alter microbiome structure, but such information has not yet been fully utilized in data models. To address these issues, a highly explainable deep learning (DL) method called Meta\u2010Spec is proposed. Using a deep neural network (DNN)\u2010based approach, it encodes and embeds refined host variables with microbiome features, enabling the detection of multiple diseases simultaneously. Experiments show that Meta\u2010Spec outperforms regular machine learning (ML) strategies for multilabel disease screening in several cohorts. More importantly, Meta\u2010Spec successfully detects comorbidities that are often missed by other approaches. In addition, for its high interpretability, Meta\u2010Spec captures key factors that shape disease patterns from host variables and microbes. Hence, these efforts improve the feasibility and sensitivity of microbiome\u2010based disease screening in practical scenarios, representing a significant step toward personalized medicine and better health outcomes.<\/jats:p>","DOI":"10.1002\/aisy.202300342","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T03:00:25Z","timestamp":1695351625000},"update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Host\u2010Variable\u2010Embedding Augmented Microbiome\u2010Based Simultaneous Detection of Multiple Diseases by Deep Learning"],"prefix":"10.1002","volume":"5","author":[{"given":"Shunyao","family":"Wu","sequence":"first","affiliation":[{"name":"College of Computer Science and Technology Qingdao University Qingdao 266071 China"}]},{"given":"Zhiruo","family":"Li","sequence":"additional","affiliation":[{"name":"School of Mathematics and Statistics Qingdao University Qingdao 266071 China"}]},{"given":"Yuzhu","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Computer Science and Technology Qingdao University Qingdao 266071 China"}]},{"given":"Mingqian","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Computer Science and Technology Qingdao University Qingdao 266071 China"}]},{"given":"Yangyang","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Computer Science and Technology Qingdao University Qingdao 266071 China"}]},{"given":"Jieqi","family":"Xing","sequence":"additional","affiliation":[{"name":"College of Computer Science and Technology Qingdao University Qingdao 266071 China"}]},{"given":"Fengyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Computer Science and Technology Qingdao University Qingdao 266071 China"}]},{"given":"Shi","family":"Huang","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry The University of Hong Kong, Hong Kong Hong Kong SAR China"}]},{"given":"Rob","family":"Knight","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Center for Microbiome Innovation University of California at San Diego San Diego CA 92093 USA"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-2144-1991","authenticated-orcid":false,"given":"Xiaoquan","family":"Su","sequence":"additional","affiliation":[{"name":"College of Computer Science and Technology Qingdao University Qingdao 266071 China"}]}],"member":"311","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.11.024"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4236"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01973-8"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa542"},{"key":"e_1_2_9_6_1","first-page":"00150\u201320","volume":"5","author":"Su X.","year":"2020","journal-title":"mSsystems"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0029-9"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-020-00724-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00031-18"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.04.054"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013797722156"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.240"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665106005143"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-1536"},{"key":"e_1_2_9_15_1","unstructured":"J.Ma Z.Zhao X.Yi J.Chen L.Hong E. 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