{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:12:03Z","timestamp":1792663923881,"version":"4.5.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T00:00:00Z","timestamp":1728691200000},"content-version":"vor","delay-in-days":285,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"KHIDI","doi-asserted-by":"publisher","award":["HI22C1318 N-23-NM-CA01-S01 N-23-NT-CA01-S01"],"award-info":[{"award-number":["HI22C1318 N-23-NM-CA01-S01 N-23-NT-CA01-S01"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021520","name":"National Supercomputing Center","doi-asserted-by":"publisher","award":["KSC-2023-CRE-0526"],"award-info":[{"award-number":["KSC-2023-CRE-0526"]}],"id":[{"id":"10.13039\/501100021520","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003708","name":"Korea Institute of Science and Technology Information","doi-asserted-by":"crossref","award":["K-23-L02-C04-S01"],"award-info":[{"award-number":["K-23-L02-C04-S01"]}],"id":[{"id":"10.13039\/501100003708","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003710","name":"KHIDI","doi-asserted-by":"publisher","award":["HI22C1318 N-23-NM-CA01-S01 N-23-NT-CA01-S01"],"award-info":[{"award-number":["HI22C1318 N-23-NM-CA01-S01 N-23-NT-CA01-S01"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021520","name":"National Supercomputing Center","doi-asserted-by":"publisher","award":["KSC-2023-CRE-0526"],"award-info":[{"award-number":["KSC-2023-CRE-0526"]}],"id":[{"id":"10.13039\/501100021520","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003708","name":"Korea Institute of Science and Technology Information","doi-asserted-by":"crossref","award":["K-23-L02-C04-S01"],"award-info":[{"award-number":["K-23-L02-C04-S01"]}],"id":[{"id":"10.13039\/501100003708","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The development of therapeutic agents has mainly focused on designing small molecules to modulate target proteins or genes which are conventionally druggable. Therefore, targeted protein degradation (TPD) for undruggable cases has emerged as promising pharmaceutical approach. TPD, often referred PROTACs (PROteolysis TArgeting Chimeras), uses a linker to degrade target proteins by hijacking the ubiquitination system. Therefore, unravel the relationship including reversal and co-expression between E3 ligands and other possible target genes in various human tissues is essential to mitigate off-target effects of TPD. Here, we developed the atlas of E3 ligases in human tissues (ELiAH), to prioritize E3 ligase\u2013target gene pairs for TPD. Leveraging over 2900 of RNA-seq profiles consisting of 11 human tissues from the GTEx (genotype-tissue expression) consortium, users of ELiAH can identify tissue-specific genes and E3 ligases (FDR P-value of Mann\u2013Whitney test\u2009&amp;lt;\u2009.05). ELiAH unravels 933\u2009830 relationships consisting of 614 E3 ligases and 20\u2009924 of expressed genes considering degree of tissue specificity, which are indispensable for ubiquitination based TPD development. In addition, docking properties of those relationships are also modeled using RosettaDock. Therefore, ELiAH presents comprehensive repertoire of E3 ligases for ubiquitination-based TPD drug development avoiding off-target effects.<\/jats:p>\n               <jats:p>Database URL: https:\/\/eliahdb.org<\/jats:p>","DOI":"10.1093\/database\/baae111","type":"journal-article","created":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T15:37:57Z","timestamp":1728747477000},"source":"Crossref","is-referenced-by-count":11,"title":["ELiAH: the atlas of E3 ligases in human tissues for targeted protein degradation with reduced off-target effect"],"prefix":"10.1093","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5803-0670","authenticated-orcid":false,"given":"Hyojung","family":"Paik","sequence":"first","affiliation":[{"name":"Center for Supercomputing Application, Korea Institute of Science and Technology Information (KISTI) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]},{"name":"Center for Biomedical Computing, Korea Institute of Science and Technology Information (KISTI) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]},{"name":"Department of Data and HPC Science, University of Science and Technology (UST) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunryong","family":"Oh","sequence":"additional","affiliation":[{"name":"Center for Supercomputing Application, Korea Institute of Science and Technology Information (KISTI) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]},{"name":"Center for Biomedical Computing, Korea Institute of Science and Technology Information (KISTI) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]},{"name":"Department of Data and HPC Science, University of Science and Technology (UST) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajid","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Applied AI, University of Science and Technology (UST) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangjae","family":"Seo","sequence":"additional","affiliation":[{"name":"Center for Supercomputing Application, Korea Institute of Science and Technology Information (KISTI) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon Woo","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Nanotubes and Nanostructured Composites, Sungkyunkwan University , 2066 Seobu-ro, Suwon 16419,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Lyun","family":"Ko","sequence":"additional","affiliation":[{"name":"Center for Biomedical Computing, Korea Institute of Science and Technology Information (KISTI) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]},{"name":"Department of Data and HPC Science, University of Science and Technology (UST) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Supercomputing Application, Korea Institute of Science and Technology Information (KISTI) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]},{"name":"Center for Biomedical Computing, Korea Institute of Science and Technology Information (KISTI) , 245 Daehak-ro, Daejeon 34141,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,10,12]]},"reference":[{"key":"2024101215373432300_R1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00966-4","article-title":"Targeted protein degradation: mechanisms, strategies and application","volume":"7","author":"Zhao","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"2024101215373432300_R2","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.cbpa.2019.11.012","article-title":"Targeted protein degradation: current and future challenges","volume":"56","author":"Hanzl","year":"2020","journal-title":"Curr Opin Chem Biol"},{"key":"2024101215373432300_R3","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.chembiol.2020.07.020","article-title":"PROTACs: an emerging therapeutic modality in precision medicine","volume":"27","author":"Nalawansha","year":"2020","journal-title":"Cell Chem Biol"},{"key":"2024101215373432300_R4","doi-asserted-by":"publisher","first-page":"8554","DOI":"10.1073\/pnas.141230798","article-title":"Protacs: chimeric molecules that target proteins to the Skp1\u2013Cullin\u2013F box complex for ubiquitination and degradation","volume":"98","author":"Sakamoto","year":"2001","journal-title":"Proc Natl Acad Sci"},{"key":"2024101215373432300_R5","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC targeted protein degraders: the past is prologue","volume":"21","author":"B\u00e9k\u00e9s","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"2024101215373432300_R6","doi-asserted-by":"publisher","first-page":"D1381","DOI":"10.1093\/nar\/gkaa807","article-title":"PROTAC-DB: an online database of PROTACs","volume":"49","author":"Weng","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2024101215373432300_R7","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baab010","article-title":"UbiNet 2.0: a verified, classified, annotated and updated database of E3 ubiquitin ligase\u2013substrate interactions","volume":"2021","author":"Li","year":"2021","journal-title":"Database"},{"key":"2024101215373432300_R8","doi-asserted-by":"publisher","first-page":"5740","DOI":"10.1039\/D2CS00200K","article-title":"Target and tissue selectivity of PROTAC degraders","volume":"51","author":"Guenette","year":"2022","journal-title":"Chem Soc Rev"},{"key":"2024101215373432300_R9","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The genotype-tissue expression (GTEx) project","volume":"45","author":"Lonsdale","year":"2013","journal-title":"Nat Genet"},{"key":"2024101215373432300_R10","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1093\/bioinformatics\/btw216","article-title":"ARACNe-AP: gene network reverse engineering through adaptive partitioning inference of mutual information","volume":"32","author":"Lachmann","year":"2016","journal-title":"Bioinformatics"},{"key":"2024101215373432300_R11","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2024101215373432300_R12","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2024101215373432300_R13","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat Methods"},{"key":"2024101215373432300_R14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2024101215373432300_R15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022477","article-title":"Benchmarking and analysis of protein docking performance in Rosetta v3. 2","volume":"6","author":"Chaudhury","year":"2011","journal-title":"PloS One"},{"key":"2024101215373432300_R16","doi-asserted-by":"publisher","first-page":"D368","DOI":"10.1093\/nar\/gkad1011","article-title":"AlphaFold Protein Structure Database in 2024: providing structure coverage for over 214 million protein sequences","volume":"52","author":"Varadi","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2024101215373432300_R17","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/s41586-022-05235-6","article-title":"Antibody targeting of E3 ubiquitin ligases for receptor degradation","volume":"610","author":"Marei","year":"2022","journal-title":"Nature"},{"key":"2024101215373432300_R18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42233-2","article-title":"Expanding PROTACtable genome universe of E3 ligases","volume":"14","author":"Liu","year":"2023","journal-title":"Nat Commun"},{"key":"2024101215373432300_R19","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04267-6","article-title":"Identification of histone methyltransferase NSD2 as an important oncogenic gene in colorectal cancer","volume":"12","author":"Zhao","year":"2021","journal-title":"Cell Death Dis"},{"key":"2024101215373432300_R20","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1016\/j.celrep.2017.10.001","article-title":"Understanding tissue-specific gene regulation","volume":"21","author":"Sonawane","year":"2017","journal-title":"Cell Rep"},{"key":"2024101215373432300_R21","doi-asserted-by":"publisher","first-page":"3886","DOI":"10.1039\/D2CS00141A","article-title":"Degrader-antibody conjugates","volume":"51","author":"Dragovich","year":"2022","journal-title":"Chem Soc Rev"},{"key":"2024101215373432300_R22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01027-z","article-title":"Comprehensive analysis of normal adjacent to tumor transcriptomes","volume":"8","author":"Aran","year":"2017","journal-title":"Nat Commun"}],"container-title":["Database"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/database\/article-pdf\/doi\/10.1093\/database\/baae111\/59735305\/baae111.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/database\/article-pdf\/doi\/10.1093\/database\/baae111\/59735305\/baae111.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T15:37:59Z","timestamp":1728747479000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/database\/article\/doi\/10.1093\/database\/baae111\/7819842"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024]]},"references-count":22,"URL":"https:\/\/doi.org\/10.1093\/database\/baae111","relation":{},"ISSN":["1758-0463"],"issn-type":[{"value":"1758-0463","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024]]},"published":{"date-parts":[[2024]]},"article-number":"baae111"}}