{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:03:34Z","timestamp":1789995814114,"version":"4.0.1"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":263,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005273","name":"Natural Science Foundation of Yunnan Province","doi-asserted-by":"publisher","award":["202302AA310025"],"award-info":[{"award-number":["202302AA310025"]}],"id":[{"id":"10.13039\/501100005273","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Genomics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatic ischemia\u2013reperfusion injury (HIRI) is a major cause of early allograft dysfunction after liver transplantation, but its post\u2010transcriptional regulation remains poorly understood. This study aimed to characterize alternative splicing (AS) events in HIRI and explore a potential association network involving RNA\u2010binding proteins (RBPs), AS, and immune responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the GSE151648 dataset (80 paired samples from 40 patients), we identified regulated alternative splicing (RAS) events and analyzed dynamic changes in immune cell populations. An RBP\u2010RAS co\u2010expression network was constructed, and single\u2010cell data (GSE171539, one donor, three time points) were used to explore cell\u2010type\u2010specific expression of key RBPs in a qualitative, hypothesis\u2010generating capacity. RBP expression changes were validated in an independent microarray cohort (GSE12720, 20 paired biopsies) and cross\u2010validated with Human Protein Atlas liver proteomic data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mild IRI (IRI\u2212) samples mainly exhibited alternative 5\u2009\n                      <jats:sup>\u2032<\/jats:sup>\n                      \/3\u2009\n                      <jats:sup>\u2032<\/jats:sup>\n                      splice site events, whereas severe IRI (IRI+) samples were characterized by intron retention and overlapping exons, suggesting that severe injury may involve spliceosomal dysfunction. Post\u2010transplantation, activated mast cells and NK cells increased, with a shift toward M0 macrophages and a decrease in M2 macrophages. Thirty immune\u2010related RAS events significantly correlated with immune cell proportions (|\n                      <jats:italic>r<\/jats:italic>\n                      | \u2265 0.5,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01). An RBP\u2010RAS network comprising 43 differentially expressed RBPs was constructed, showing coordinated co\u2010variation between splicing factors and immune\u2010associated splicing events. Single\u2010cell analysis further revealed cell\u2010type\u2010specific expression patterns of multiple RBPs across hepatocytes, endothelial cells, and immune populations. External validation in GSE12720 confirmed that 39 of 42 detected RBPs (93%) were consistently upregulated post\u2010reperfusion, and the Human Protein Atlas confirmed protein\u2010level expression for 25 of 43 RBPs (58%) in normal liver tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study suggests that mild and severe HIRI are associated with distinct splicing programs and that these changes are closely associated with immune microenvironment remodeling, supporting the hypothesis of an RBP\u2010AS\u2010immune regulatory network. These findings, in which the RBP expression changes were independently validated in an external cohort, provide a basis for generating hypotheses regarding post\u2010transcriptional regulation in HIRI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijog\/4835678","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:13:11Z","timestamp":1789992791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive and Combined Omics Analysis Reveals Immune\u2013Infiltration\u2010Associated Alternative Splicing and RBP Regulators Contributing to Ischemia\u2013Reperfusion Injury in Liver Transplantation"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3745-8494","authenticated-orcid":false,"given":"Bincheng","family":"Gui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3302-823X","authenticated-orcid":false,"given":"Hanfei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i18.4438"},{"key":"e_1_2_15_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2005.03.134"},{"key":"e_1_2_15_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/medicina61091710"},{"key":"e_1_2_15_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14091"},{"key":"e_1_2_15_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.225"},{"key":"e_1_2_15_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2023.03.003"},{"key":"e_1_2_15_7_2","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2023.0099"},{"key":"e_1_2_15_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08909"},{"key":"e_1_2_15_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060614-034316"},{"key":"e_1_2_15_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3778"},{"key":"e_1_2_15_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2164"},{"key":"e_1_2_15_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1276"},{"key":"e_1_2_15_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2013.04.004"},{"key":"e_1_2_15_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24098216"},{"key":"e_1_2_15_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.02.009"},{"key":"e_1_2_15_16_2","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S468828"},{"key":"e_1_2_15_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31324"},{"key":"e_1_2_15_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000330"},{"key":"e_1_2_15_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0201-4"},{"key":"e_1_2_15_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_15_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2021.1940037"},{"key":"e_1_2_15_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337"},{"key":"e_1_2_15_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.04.031"},{"key":"e_1_2_15_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.06.029"},{"key":"e_1_2_15_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3813"},{"key":"e_1_2_15_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.130"},{"key":"e_1_2_15_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_2_15_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr483"},{"key":"e_1_2_15_29_2","doi-asserted-by":"publisher","DOI":"10.5351\/CSAM.2015.22.6.665"},{"key":"e_1_2_15_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2013.08.021"},{"key":"e_1_2_15_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01193"},{"key":"e_1_2_15_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2025.168152"},{"key":"e_1_2_15_33_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI162940"},{"key":"e_1_2_15_34_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i17.3043"},{"key":"e_1_2_15_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2010.153"},{"key":"e_1_2_15_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2023.08.002"},{"key":"e_1_2_15_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201500117"},{"key":"e_1_2_15_38_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.177790.114"},{"key":"e_1_2_15_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/petr.12413"},{"key":"e_1_2_15_40_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000111286.23110.F8"},{"key":"e_1_2_15_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-019-00698-1"},{"key":"e_1_2_15_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2012_126"},{"key":"e_1_2_15_43_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2022.11504"},{"key":"e_1_2_15_44_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001411"},{"key":"e_1_2_15_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.11.001"},{"key":"e_1_2_15_46_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.52691"},{"key":"e_1_2_15_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.09.078"},{"key":"e_1_2_15_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep20248"},{"key":"e_1_2_15_49_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.711633"},{"key":"e_1_2_15_50_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200502088"},{"key":"e_1_2_15_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2016.05.004"},{"key":"e_1_2_15_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20975-0"},{"key":"e_1_2_15_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07924"},{"key":"e_1_2_15_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2137"},{"key":"e_1_2_15_55_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2009.02557.x"},{"key":"e_1_2_15_56_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"}],"container-title":["International Journal of Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ijog\/4835678","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/ijog\/4835678","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ijog\/4835678","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:13:13Z","timestamp":1789992793000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/ijog\/4835678"}},"subtitle":[],"editor":[{"given":"Neetu","family":"Rawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":56,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/ijog\/4835678"],"URL":"https:\/\/doi.org\/10.1155\/ijog\/4835678","archive":["Portico"],"relation":{},"ISSN":["2314-436X","2314-4378"],"issn-type":[{"value":"2314-436X","type":"print"},{"value":"2314-4378","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"4835678"}}