IsoformMapper: a web application for protein-level comparison of splice variants through structural community analysis. Vergara, A., Hernández-Verdeja, T., Ojeda-May, P., Ramirez, L., Edler, D., Rosvall, M., & Strand, Å. RNA, 32(1):1–20, January, 2026. Company: Cold Spring Harbor Laboratory Press Distributor: Cold Spring Harbor Laboratory Press Institution: Cold Spring Harbor Laboratory Press Label: Cold Spring Harbor Laboratory Press Publisher: Cold Spring Harbor Lab![IsoformMapper: a web application for protein-level comparison of splice variants through structural community analysis [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Alternative splicing (AS) enables cells to produce multiple protein isoforms from single genes, fine-tuning protein function across numerous cellular processes. However, despite its biological importance, researchers lack effective tools to compare the domain composition of AS-derived protein isoforms because such comparisons require both structural data and specialized methods. Recent advances in AI-driven protein structure prediction, particularly AlphaFold2, now make accurate structural determination of splicing isoforms accessible, enabling functional AS analysis at the protein structure level. Here, we present IsoformMapper, a web resource that analyzes AS through network community analysis of protein structures. This approach captures 3D physical interactions between protein regions often missed by traditional domain analysis, enabling structural comparisons of isoforms across any biological system. We illustrate our tool by analyzing validated human Bcl-X protein isoforms, revealing how AS creates distinct community structures with antagonistic functional roles. As a proof of concept, we apply our tool to investigate how GENOMES UNCOUPLED1 (GUN1)–dependent retrograde signaling regulates plant de-etiolation through alternative splicing in Arabidopsis. In response to light, gun1 shows alterations in spliceosome component expression, suggesting that GUN1 contributes to AS regulation of genes essential for photosynthetic establishment. The gun1 mutant displays altered splice variant ratios for PNSL2, CHAOS, and SIG5. Our tool reveals that these isoforms form distinct protein community structures, demonstrating how AS impacts protein function and validating IsoformMapper's practical value.
@article{vergara_isoformmapper_2026,
title = {{IsoformMapper}: a web application for protein-level comparison of splice variants through structural community analysis},
volume = {32},
issn = {1355-8382, 1469-9001},
shorttitle = {{IsoformMapper}},
url = {http://rnajournal.cshlp.org/content/32/1/1},
doi = {10.1261/rna.080738.125},
abstract = {Alternative splicing (AS) enables cells to produce multiple protein isoforms from single genes, fine-tuning protein function across numerous cellular processes. However, despite its biological importance, researchers lack effective tools to compare the domain composition of AS-derived protein isoforms because such comparisons require both structural data and specialized methods. Recent advances in AI-driven protein structure prediction, particularly AlphaFold2, now make accurate structural determination of splicing isoforms accessible, enabling functional AS analysis at the protein structure level. Here, we present IsoformMapper, a web resource that analyzes AS through network community analysis of protein structures. This approach captures 3D physical interactions between protein regions often missed by traditional domain analysis, enabling structural comparisons of isoforms across any biological system. We illustrate our tool by analyzing validated human Bcl-X protein isoforms, revealing how AS creates distinct community structures with antagonistic functional roles. As a proof of concept, we apply our tool to investigate how GENOMES UNCOUPLED1 (GUN1)–dependent retrograde signaling regulates plant de-etiolation through alternative splicing in Arabidopsis. In response to light, gun1 shows alterations in spliceosome component expression, suggesting that GUN1 contributes to AS regulation of genes essential for photosynthetic establishment. The gun1 mutant displays altered splice variant ratios for PNSL2, CHAOS, and SIG5. Our tool reveals that these isoforms form distinct protein community structures, demonstrating how AS impacts protein function and validating IsoformMapper's practical value.},
language = {en},
number = {1},
urldate = {2025-12-18},
journal = {RNA},
author = {Vergara, Alexander and Hernández-Verdeja, Tamara and Ojeda-May, Pedro and Ramirez, Leonor and Edler, Daniel and Rosvall, Martin and Strand, Åsa},
month = jan,
year = {2026},
pmid = {41136341},
note = {Company: Cold Spring Harbor Laboratory Press
Distributor: Cold Spring Harbor Laboratory Press
Institution: Cold Spring Harbor Laboratory Press
Label: Cold Spring Harbor Laboratory Press
Publisher: Cold Spring Harbor Lab},
keywords = {alternative splicing, plastid retrograde signaling},
pages = {1--20},
}
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However, despite its biological importance, researchers lack effective tools to compare the domain composition of AS-derived protein isoforms because such comparisons require both structural data and specialized methods. Recent advances in AI-driven protein structure prediction, particularly AlphaFold2, now make accurate structural determination of splicing isoforms accessible, enabling functional AS analysis at the protein structure level. Here, we present IsoformMapper, a web resource that analyzes AS through network community analysis of protein structures. This approach captures 3D physical interactions between protein regions often missed by traditional domain analysis, enabling structural comparisons of isoforms across any biological system. We illustrate our tool by analyzing validated human Bcl-X protein isoforms, revealing how AS creates distinct community structures with antagonistic functional roles. As a proof of concept, we apply our tool to investigate how GENOMES UNCOUPLED1 (GUN1)–dependent retrograde signaling regulates plant de-etiolation through alternative splicing in Arabidopsis. In response to light, gun1 shows alterations in spliceosome component expression, suggesting that GUN1 contributes to AS regulation of genes essential for photosynthetic establishment. The gun1 mutant displays altered splice variant ratios for PNSL2, CHAOS, and SIG5. 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