{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:59:55Z","timestamp":1783040395690,"version":"3.54.6"},"reference-count":74,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T00:00:00Z","timestamp":1658016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science Foundation Ireland (SFI)","award":["18\/SPP\/3522"],"award-info":[{"award-number":["18\/SPP\/3522"]}]},{"name":"Science Foundation Ireland (SFI)","award":["14\/IA\/2395"],"award-info":[{"award-number":["14\/IA\/2395"]}]},{"name":"National Children\u2019s Research Centre\/Children\u2019s Health Ireland","award":["18\/SPP\/3522"],"award-info":[{"award-number":["18\/SPP\/3522"]}]},{"name":"National Children\u2019s Research Centre\/Children\u2019s Health Ireland","award":["14\/IA\/2395"],"award-info":[{"award-number":["14\/IA\/2395"]}]},{"name":"Precision Oncology Ireland","award":["18\/SPP\/3522"],"award-info":[{"award-number":["18\/SPP\/3522"]}]},{"name":"Precision Oncology Ireland","award":["14\/IA\/2395"],"award-info":[{"award-number":["14\/IA\/2395"]}]},{"name":"the SFI Investigator","award":["18\/SPP\/3522"],"award-info":[{"award-number":["18\/SPP\/3522"]}]},{"name":"the SFI Investigator","award":["14\/IA\/2395"],"award-info":[{"award-number":["14\/IA\/2395"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alternative mRNA splicing is common in cancers. In BRAF V600E-mutated malignant melanoma, a frequent mechanism of acquired resistance to BRAF inhibitors involves alternative splicing (AS) of BRAF. The resulting shortened BRAF protein constitutively dimerizes and conveys drug resistance. Here, we have analysed AS in SK-MEL-239 melanoma cells and a BRAF inhibitor (vemurafenib)-resistant derivative that expresses an AS, shortened BRAF V600E transcript. Transcriptome analysis showed differential expression of spliceosome components between the two cell lines. As there is no consensus approach to analysing AS events, we used and compared four common AS softwares based on different principles, DEXSeq, rMATS, ASpli, and LeafCutter. Two of them correctly identified the BRAF V600E AS in the vemurafenib-resistant cells. Only 12 AS events were identified by all four softwares. Testing the AS predictions experimentally showed that these overlapping predictions are highly accurate. Interestingly, they identified AS caused alterations in the expression of melanin synthesis and cell migration genes in the vemurafenib-resistant cells. This analysis shows that combining different AS analysis approaches produces reliable results and meaningful, biologically testable hypotheses.<\/jats:p>","DOI":"10.3390\/biom12070993","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T21:00:28Z","timestamp":1658091628000},"page":"993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Analysis of Alternative mRNA Splicing in Vemurafenib-Resistant Melanoma Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3826-7582","authenticated-orcid":false,"given":"Honey","family":"Bokharaie","sequence":"first","affiliation":[{"name":"Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, D04 V1W8 Dublin 4, Ireland"},{"name":"Drug Research Program, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5777-5016","authenticated-orcid":false,"given":"Walter","family":"Kolch","sequence":"additional","affiliation":[{"name":"Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, D04 V1W8 Dublin 4, Ireland"},{"name":"Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Krstic","sequence":"additional","affiliation":[{"name":"Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, D04 V1W8 Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0140-6736(18)31559-9","article-title":"Melanoma","volume":"392","author":"Schadendorf","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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