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Research: Alternative splicing generates HER2 isoform diversity underlying antibody–drug conjugate resistance in breast cancer
- Gabriela D.A. Guardia,
- Carlos H. dos Anjos,
- Aline Rangel-Pozzo,
- Filipe F. dos Santos,
- Alexander Birbrair,
- Paula F. Asprino,
- Anamaria A. Camargo,
- and Pedro A.F. Galante
Genome Res. September 2025 35: 1942-1958; Published in Advance July 15, 2025, doi:10.1101/gr.280304.124
.... 2007; Turpin et al. 2016). Thus, a deeper understanding of these resistance mechanisms remains a critical challenge in overcoming and managing breast cancer tumors expressing HER2.Alternative splicing, a fundamental post-transcriptional process in eukaryotic gene expression, allows a single gene locus...
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Method: Reference-informed prediction of alternative splicing and splicing-altering mutations from sequences
- Chencheng Xu,
- Suying Bao,
- Ye Wang,
- Wenxing Li,
- Hao Chen,
- Yufeng Shen,
- Tao Jiang,
- and Chaolin Zhang
Genome Res. July 2024 34: 1052-1065; Published in Advance July 26, 2024, doi:10.1101/gr.279044.124
...data for the dual-sequence mode are splicing-altering genetic variants or mutations, but unfortunately, no such large-scale mutation data sets with experimentally determined impacts are available. To overcome this limitation, DeltaSplice randomly samples pairs of gene sequences with varying degrees...
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Method: PRAM: a novel pooling approach for discovering intergenic transcripts from large-scale RNA sequencing experiments
- Peng Liu,
- Alexandra A. Soukup,
- Emery H. Bresnick,
- Colin N. Dewey,
- and Sündüz Keleş
Genome Res. November 2020 30: 1655-1666; Published in Advance September 21, 2020, doi:10.1101/gr.252445.119
...splice junctions, while performing competitively in detecting exonic nucleotides. Applying PRAM to 30 human ENCODE RNA-seq data sets identified unannotated transcripts with epigenetic and RAMPAGE signatures similar to those of recently annotated transcripts. In a case study, we discovered...
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Resource: Large-scale analysis of branchpoint usage across species and cell lines
- Allison J. Taggart,
- Chien-Ling Lin,
- Barsha Shrestha,
- Claire Heintzelman,
- Seongwon Kim,
- and William G. Fairbrother
Genome Res. April 2017 27: 639-649; Published in Advance January 24, 2017, doi:10.1101/gr.202820.115
...RNA:pre-mRNA recognition, and the role of branch site selection in alternative splicing. The branch site is an obligate signal for intron splicing, yet in higher eukaryotes it lacks the strong sequence motifs associated with the 5′ss and 3′ss. A general region of branchpoint formation is observed in an expected range...
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Research: Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks
- Endre Sebestyén,
- Babita Singh,
- Belén Miñana,
- Amadís Pagès,
- Francesca Mateo,
- Miguel Angel Pujana,
- Juan Valcárcel,
- and Eduardo Eyras
Genome Res. June 2016 26: 732-744; Published in Advance April 13, 2016, doi:10.1101/gr.199935.115
...Large-scale analysis of and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks Endre Sebestyén1,5, Babita Singh1,5, Belén Miñana1,2, Amadís Pagès1, Francesca Mateo3, Miguel Angel Pujana3, Juan Valcárcel1,2,4 and Eduardo Eyras1,4 1Universitat Pompeu Fabra, E...
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Method: Large-scale identification of chemically induced mutations in Drosophila melanogaster
- Nele A. Haelterman,
- Lichun Jiang,
- Yumei Li,
- Vafa Bayat,
- Hector Sandoval,
- Berrak Ugur,
- Kai Li Tan,
- Ke Zhang,
- Danqing Bei,
- Bo Xiong,
- Wu-Lin Charng,
- Theodore Busby,
- Adeel Jawaid,
- Gabriela David,
- Manish Jaiswal,
- Koen J.T. Venken,
- Shinya Yamamoto,
- Rui Chen,
- and Hugo J. Bellen
Genome Res. October 2014 24: 1707-1718; Published in Advance September 25, 2014, doi:10.1101/gr.174615.114
...mutations in a higher eukaryote. We show that WGS can be applied on a large scale in Drosophila to identify ;70% of the mutations, provided that SNVs are extensively filtered and rough mapping is performed. Upon filtering out those SNVs that are in noncoding regions and those that lead to synonymous changes...
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Method: Genome-reconstruction for eukaryotes from complex natural microbial communities
- Patrick T. West,
- Alexander J. Probst,
- Igor V. Grigoriev,
- Brian C. Thomas,
- and Jillian F. Banfield
Genome Res. April 2018 28: 569-580; Published in Advance March 1, 2018, doi:10.1101/gr.228429.117
...complex promoter regions, regulatory signals, and genes spliced into introns and exons, variable between species. For this reason, it is not surprising that we found that prokaryotic gene predictors underperform when used on eukaryotic sequences. This can impact binning by affecting taxonomic profiling...
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Research: Allele-specific alternative splicing and its functional genetic variants in human tissues
- Kofi Amoah,
- Yun-Hua Esther Hsiao,
- Jae Hoon Bahn,
- Yiwei Sun,
- Christina Burghard,
- Boon Xin Tan,
- Ei-Wen Yang,
- and Xinshu Xiao
Genome Res. March 2021 31: 359-371; Published in Advance January 15, 2021, doi:10.1101/gr.265637.120
...applied to understanding the regulatory effects of genetic variants on splicing. However, it is still challenging to go beyond apparent association to pinpoint functional variants. To fill in this gap, we utilized large-scale data sets of the Genotype-Tissue Expression (GTEx) project to study genetically...
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Research: Dynamic shifts in occupancy by TAL1 are guided by GATA factors and drive large-scale reprogramming of gene expression during hematopoiesis
- Weisheng Wu,
- Christapher S. Morrissey,
- Cheryl A. Keller,
- Tejaswini Mishra,
- Maxim Pimkin,
- Gerd A. Blobel,
- Mitchell J. Weiss,
- and Ross C. Hardison
Genome Res. December 2014 24: 1945-1962; Published in Advance October 15, 2014, doi:10.1101/gr.164830.113
...Dynamic shifts in occupancy by TAL1 are guided by GATA factors and drive large-scale reprogramming of gene expression during hematopoiesis Weisheng Wu 1 , 4 , Christapher S. Morrissey 1 , Cheryl A. Keller 1 , Tejaswini Mishra 1 , Maxim...
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Research: RNA editing in nascent RNA affects pre-mRNA splicing
- Yun-Hua Esther Hsiao,
- Jae Hoon Bahn,
- Yun Yang,
- Xianzhi Lin,
- Stephen Tran,
- Ei-Wen Yang,
- Giovanni Quinones-Valdez,
- and Xinshu Xiao
Genome Res. June 2018 28: 812-823; Published in Advance May 3, 2018, doi:10.1101/gr.231209.117
..., revealed remarkable interplay between RNA editing and splicing and expanded the repertoire of functional RNA editing sites.The maturation of eukaryotic mRNAs involves an intricate series of molecular processes that modify newly synthesized RNA molecules, such as 5′ capping, splicing, RNA editing...
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