{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T09:05:49Z","timestamp":1774602349996,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61872094"],"award-info":[{"award-number":["61872094"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["2017SHZDZX01"],"award-info":[{"award-number":["2017SHZDZX01"]}]},{"name":"Information Technology Facility"},{"name":"Shanghai Institute for Biological Sciences, Chinese Academy of Sciences"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61872094"],"award-info":[{"award-number":["61872094"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["2018SHZDZX01"],"award-info":[{"award-number":["2018SHZDZX01"]}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["315896"],"award-info":[{"award-number":["315896"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001695","name":"JST","doi-asserted-by":"publisher","award":["JPMJAC1503"],"award-info":[{"award-number":["JPMJAC1503"]}],"id":[{"id":"10.13039\/501100001695","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NEXT","award":["19H04169"],"award-info":[{"award-number":["19H04169"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Exploring the relationship between human proteins and abnormal phenotypes is of great importance in the prevention, diagnosis and treatment of diseases. The human phenotype ontology (HPO) is a standardized vocabulary that describes the phenotype abnormalities encountered in human diseases. However, the current HPO annotations of proteins are not complete. Thus, it is important to identify missing protein\u2013phenotype associations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We propose HPOFiller, a graph convolutional network (GCN)-based approach, for predicting missing HPO annotations. HPOFiller has two key GCN components for capturing embeddings from complex network structures: (i) S-GCN for both protein\u2013protein interaction network and HPO semantic similarity network to utilize network weights; (ii) Bi-GCN for the protein\u2013phenotype bipartite graph to conduct message passing between proteins and phenotypes. The core idea of HPOFiller is to repeat run these two GCN modules consecutively over the three networks, to refine the embeddings. Empirical results of extremely stringent evaluation avoiding potential information leakage including cross-validation and temporal validation demonstrates that HPOFiller significantly outperforms all other state-of-the-art methods. In particular, the ablation study shows that batch normalization contributes the most to the performance. The further examination offers literature evidence for highly ranked predictions. Finally using known disease-HPO term associations, HPOFiller could suggest promising, unknown disease\u2013gene associations, presenting possible genetic causes of human disorders.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availabilityand implementation<\/jats:title>\n                  <jats:p>https:\/\/github.com\/liulizhi1996\/HPOFiller.<\/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\/btab224","type":"journal-article","created":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T11:08:21Z","timestamp":1617620901000},"page":"3328-3336","source":"Crossref","is-referenced-by-count":19,"title":["HPOFiller: identifying missing protein\u2013phenotype associations by graph convolutional network"],"prefix":"10.1093","volume":"37","author":[{"given":"Lizhi","family":"Liu","sequence":"first","affiliation":[{"name":"School of Computer Science, Fudan University , Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Mamitsuka","sequence":"additional","affiliation":[{"name":"Bioinformatics Center, Institute for Chemical Research, Kyoto University , Uji, Kyoto Prefecture 611-0011, Japan"},{"name":"Department of Computer Science, Aalto University , Espoo, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-5312","authenticated-orcid":false,"given":"Shanfeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology for Brain-Inspired Intelligence and Shanghai Institute of Artificial Intelligence Algorithms, Fudan University , Shanghai 200433, China"},{"name":"Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University) , Ministry of Education, Shanghai 200433, China"},{"name":"Shanghai Key Lab of Intelligent Information Processing, Fudan University , Shanghai 200433, China"},{"name":"MOE Frontiers Center for Brain Science, Fudan University , Shanghai 200433, China"},{"name":"Zhangjiang Fudan International Innovation Center , Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"2023051608281843800_btab224-B1","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1634\/theoncologist.2017-0572","article-title":"Epidermal growth factor receptor tyrosine kinase inhibitors for central nervous system metastases from non-small cell lung cancer","volume":"23","author":"Ahluwalia","year":"2018","journal-title":"Oncologist"},{"key":"2023051608281843800_btab224-B2","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/s41416-020-0984-6","article-title":"Computational analysis of TP53 mutational landscape unveils key prognostic signatures and distinct pathobiological pathways in head and neck squamous cell cancer","volume":"123","author":"Caponio","year":"2020","journal-title":"Br. 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