{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:00:02Z","timestamp":1772118002145,"version":"3.50.1"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31771165"],"award-info":[{"award-number":["31771165"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971064"],"award-info":[{"award-number":["81971064"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Intelligent Systems"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p>Alternative splicing (AS) is a fundamental mechanism that regulates gene expressionin both physiological and pathological processes. This article introduces ASTK, a software package covering upstream and downstream analysis of AS. Initially, ASTK offers a module to perform enrichment analysis at both the gene\u2010 and exon\u2010level to incorporate various impacts by different spliced events on a single gene. We further cluster AS genes and alternative exons into three groups based on spliced exon sizes (micro\u2010, mid\u2010, and macro\u2010), which are preferentially associated with distinct biological pathways. A major challenge in the field has been decoding the regulatory codes of splicing. ASTK adeptly extracts both sequence features and epigenetic marks associated with AS events. Through the application of machine learning algorithms, we identified pivotal features influencing the inclusion levels of most AS types. Notably, the splice site strength is a primary determinant for the inclusion levels in alternative 3\u2019\/5\u2019 splice sites (A3\/A5). For the alternative first exon and skipping exon classes, a combination of sequence and epigenetic features collaboratively dictate exon inclusion\/exclusion. Our findings underscore ASTK's capability to enhance the functional understanding of AS events and shed light on the intricacies of splicing regulation.<\/jats:p>","DOI":"10.1002\/aisy.202300594","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T21:30:25Z","timestamp":1707341425000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["ASTK: A Machine Learning\u2010Based Integrative Software for Alternative Splicing Analysis"],"prefix":"10.1002","volume":"6","author":[{"given":"Shenghui","family":"Huang","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory Medicine Ministry of Education, China School of Laboratory Medicine and Life Science Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"},{"name":"Institute of Genomic Medicine Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangshuang","family":"He","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory Medicine Ministry of Education, China School of Laboratory Medicine and Life Science Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"},{"name":"Institute of Genomic Medicine Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory Medicine Ministry of Education, China School of Laboratory Medicine and Life Science Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"},{"name":"Institute of Genomic Medicine Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Guo","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory Medicine Ministry of Education, China School of Laboratory Medicine and Life Science Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"},{"name":"Institute of Genomic Medicine Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory Medicine Ministry of Education, China School of Laboratory Medicine and Life Science Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"},{"name":"Institute of Genomic Medicine Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoxia","family":"Sun","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory Medicine Ministry of Education, China School of Laboratory Medicine and Life Science Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"},{"name":"Institute of Genomic Medicine Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linghui","family":"Cheng","sequence":"additional","affiliation":[{"name":"Scientific Research Center Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Informatics University of Edinburgh  Edinburgh EH8 9AB UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Mathematics School of Science &amp; Engineering Tulane University  New Orleans 70118 LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0909-2621","authenticated-orcid":false,"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory Medicine Ministry of Education, China School of Laboratory Medicine and Life Science Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"},{"name":"Institute of Genomic Medicine Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"},{"name":"Key Laboratory of Alzheimer's Disease of Zhejiang Province Institute of Aging Wenzhou Medical University  Wenzhou Zhejiang Province 325035 China"},{"name":"The Eye\u2010Brain Research Center State Key Laboratory of Ophthalmology Optometry and Visual Science  Wenzhou Zhejiang Province 325027 China"},{"name":"Oujiang Laboratory Zhejiang Lab for Regenerative Medicine, Vision and Brain Health  Wenzhou Zhejiang Province 325101 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060614-034316"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom5020893"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419161111"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1417-1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-016-2816-x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqac067"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-017-0004-9"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1528"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqad044"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac846"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx411"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02538-1"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.212696.116"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa237"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty606"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad111"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-018-2136-x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.070987.119"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005387"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10709-007-9139-4"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.181990.114"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108560"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46042"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201804106"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1678"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355838202021088"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/1066527041410418"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.02.001"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.86"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.03.011"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt875"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1184208"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-017-4393-z"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac994"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-13-123"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa248"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbad121"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2022.04.008"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks433"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baw035"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12311"},{"key":"e_1_2_8_44_1","unstructured":"L.Buitinck G.Louppe M.Blondel F.Pedregosa A.Mueller O.Grisel V.Niculae P.Prettenhofer A.Gramfort J.Grobler R.Layton inECML PKDD Workshop: Languages for Data Mining and Machine Learning2013 Prague Czech Republic."},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2077-3"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.09.010"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.130"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bby005"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1500"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09000"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005602"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.26.15081"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508489102"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.032"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-20979-x"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa886"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac955"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101135108"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1418"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.035"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0538-1"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.10.008"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2660805"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-12-90"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.03.013"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90202-4"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.24.10505-10514.2004"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.5.3434"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.322"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1659"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002717"}],"container-title":["Advanced Intelligent Systems"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/aisy.202300594","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T23:46:51Z","timestamp":1759880811000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/aisy.202300594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,7]]},"references-count":70,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/aisy.202300594"],"URL":"https:\/\/doi.org\/10.1002\/aisy.202300594","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.01.03.522470","asserted-by":"object"}]},"ISSN":["2640-4567","2640-4567"],"issn-type":[{"value":"2640-4567","type":"print"},{"value":"2640-4567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,7]]},"assertion":[{"value":"2023-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2300594"}}