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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
...transcripts typically encode a 185 kDa transmembrane tyrosine kinase receptor that belongs to the epidermal growth factor receptor (EGFR) family (Moasser 2007). Regarding functionalities, HER2 overexpression leads to the constitutive activation of downstream signaling pathways, including PIK3CA/AKT and MAPK...
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Method: Gene duplication is associated with gene diversification and potential neofunctionalization in lung cancer evolution
- Paul Ashford,
- Alexander M. Frankell,
- Zofia Piszka,
- Camilla S.M. Pang,
- Mahnaz Abbasian,
- Maise Al Bakir,
- Mariam Jamal-Hanjani,
- Nicholas McGranahan,
- Charles Swanton,
- and Christine A. Orengo
Genome Res. March 2026 36: 561-577; Published in Advance February 19, 2026, doi:10.1101/gr.278663.123
...under positive selection (dN/dS > 1.5). (B) FIEs in ERBB tyrosine–protein kinase paralogs EGFR* (lung), ERBB4* (lung), and ERBB2* (pancancer). (C) Ras small monomeric GTPase with LUAD FIEs in genes RRAS2 and RIT within the same FunFam. (D) Rac family small GTPase with LUSC FIEs in genes RAC1* and RAC2...
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Research: Confounding factors in assessing the enriched expression of somatic mutant allele in bulk tumor samples
- Kohei Hagiwara,
- Andrew Thrasher,
- Nadezhda V Terekhanova,
- and Jinghui Zhang
Genome Res. March 4, 2026 gr.281003.125; Published in Advance March 4, 2026, doi:10.1101/gr.281003.125
...to complement DNA-based somatic 39 mutation detection in low purity samples. Indeed, our de novo somatic indel calling from TCGA 40 RNA-seq increases the TCGA driver indel repertoire by ~ 14%, especially in samples with purity 41 < 0.4, including actionable EGFR indels in lung adenocarcinoma and FLT3 in acute...
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Method: Nanopore-based consensus sequencing enables accurate multimodal tumor cell-free DNA profiling
- Li-Ting Chen,
- Myrthe Jager,
- Dàmi Rebergen,
- Geertruid J. Brink,
- Tom van den Ende,
- Willem Vanderlinden,
- Pauline Kolbeck,
- Marc Pagès-Gallego,
- Ymke van der Pol,
- Nicolle Besselink,
- Norbert Moldovan,
- Nizar Hami,
- Wigard P. Kloosterman,
- Hanneke van Laarhoven,
- Florent Mouliere,
- Ronald Zweemer,
- Jan Lipfert,
- Sarah Derks,
- Alessio Marcozzi,
- and Jeroen de Ridder
Genome Res. April 2025 35: 886-899; Published in Advance January 13, 2025, doi:10.1101/gr.279144.124
...: In this window In a new window Figure 1. NanoRCS can identify SNVs, CNVs, and fragment size in cfDNA. (A) Healthy cfDNA (blue) and tumor ctDNA (pink) are circulated with a high curvature DNA backbone (orange) and form a double-strand circular DNA product. (B) DNA primers of random sequence and phi29 polymerase...
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Resource: A systems view on DNA damage response kinetics in Tetrahymena
- Emily Nischwitz,
- Vivien Schoonenberg,
- Rachel Mullner,
- Albert Fradera-Sola,
- Susanne Zimbelmann,
- Joshua J Smith,
- and Falk Butter
Genome Res. January 28, 2026 gr.281000.125; Published in Advance January 28, 2026, doi:10.1101/gr.281000.125
...24 0 to 8 hours) integrates over 250 paired transcriptome and proteome measurements. We 25 observe upregulation of known DNA repair proteins as well as a global dynamic response of 26 not yet characterized transcripts and proteins. Using artificial neural networks, we classify 27 different expression...
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Resource: Cell type–specific gene regulatory atlas prioritizes drug targets and repurposable medicines in Alzheimer's disease
- Yunxiao Ren,
- Ming Hu,
- Yang E. Li,
- Andrew A. Pieper,
- Jeffrey Cummings,
- and Feixiong Cheng
Genome Res. March 2026 36: 645-659; Published in Advance January 21, 2026, doi:10.1101/gr.280436.125
...–specific cis-regulatory DNA elements (CREs), we pinpoint 141 ADNC-associated genes. Using gene set enrichment analysis (GSEA) and network proximity analysis, we further identify nine candidate repurposable drugs that were associated with these ADNC-related genes. In summary, this cell type–specific multiomic...
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Perspective: Unraveling the hidden complexity of cancer through long-read sequencing
- Qiuhui Li,
- Ayse G. Keskus,
- Justin Wagner,
- Michal B. Izydorczyk,
- Winston Timp,
- Fritz J. Sedlazeck,
- Alison P. Klein,
- Justin M. Zook,
- Mikhail Kolmogorov,
- and Michael C. Schatz
Genome Res. April 2025 35: 599-620; Published in Advance March 20, 2025, doi:10.1101/gr.280041.124
...of complex rearrangement and amplification processes, such as chromothripsis, extrachromosomal DNA (ecDNA), or BFB. For example, one germline study used nanopore sequencing to identify disease-related gene losses resulting from chromothripsis in a Langer–Giedion syndrome (Lei et al. 2020). Using ONT...
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Method: CoRAL accurately resolves extrachromosomal DNA genome structures with long-read sequencing
- Kaiyuan Zhu,
- Matthew G. Jones,
- Jens Luebeck,
- Xinxin Bu,
- Hyerim Yi,
- King L. Hung,
- Ivy Tsz-Lo Wong,
- Shu Zhang,
- Paul S. Mischel,
- Howard Y. Chang,
- and Vineet Bafna
Genome Res. September 2024 34: 1344-1354; Published in Advance July 9, 2024, doi:10.1101/gr.279131.124
...(Deshpande et al. 2019; Luebeck et al. 2020; Chapman et al. 2023). Existing approaches rely on paired-end, short-read (Illumina) sequencing to identify amplicons from copy-number profiles and breakpoints, which then can be represented with an edge-weighted breakpoint graph; ecDNAs can subsequently...
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Research: Autism spectrum disorder risk genes have convergent effects on transcription and neuronal firing patterns in primary neurons
- Alekh Paranjapye,
- Rili Ahmad,
- Steven Su,
- Abraham J. Waldman,
- Jennifer E. Phillips-Cremins,
- Shuo Zhang,
- and Erica Korb
Genome Res. November 2025 35: 2433-2444; Published in Advance October 20, 2025, doi:10.1101/gr.280698.125
...modifying enzymes that target different histone sites, chromatin remodelers from different complexes, a DNA modifying enzyme, a transcription factor, and a noncatalytic chromatin-complex protein. Even with this expanded group, we successfully identified both shared gene signatures and common neuronal...
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Method: PoreMeth2 for decoding the evolution of methylome alterations with nanopore sequencing
- Gianluca Mattei,
- Marta Baragli,
- Barbara Gega,
- Alessandra Mingrino,
- Martina Chieca,
- Tommaso Ducci,
- Gianmaria Frigè,
- Luca Mazzarella,
- Romina D'Aurizio,
- Francesco De Logu,
- Romina Nassini,
- Pier Giuseppe Pelicci,
- and Alberto Magi
Genome Res. November 2025 35: 2501-2512; Published in Advance October 20, 2025, doi:10.1101/gr.280259.124
...ExpQualityPlot returns two plots representing the distribution of the number of reads used to calculate Δβ and ΔS for common CpGs between the two samples (Supplemental Fig. S39).AML sample sequencing and data preparationDNA from each of three pairs of matched AMLs was sequenced, basecalled, and aligned to the human...

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