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Research: Confounding factors in assessing the enriched expression of somatic mutant alleles in bulk tumor samples
- Kohei Hagiwara,
- Andrew Thrasher,
- Nadezhda V. Terekhanova,
- and Jinghui Zhang
Genome Res. March 4, 2026 ; Published in Advance March 4, 2026, doi:10.1101/gr.281003.125
...indel calling from TCGARNA-seq increases the TCGAdriver indel repertoire by∼14%, especially in samples with purity less than 0.4, including actionable EGFR indels in lung adenocarcinoma and FLT3 in acute myeloid leukemia. Our study not only reveals confounders in somatic mutant ASE analysis but also...
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Method: Deep structural clustering reveals hidden systematic biases in RNA sequencing data
- Qiang Su,
- Yi Long,
- Deming Gou,
- Junmin Quan,
- Xiaoming Zhou,
- and Qizhou Lian
Genome Res. November 2025 35: 2563-2577; Published in Advance September 19, 2025, doi:10.1101/gr.280713.125
...these model Gaussians to similarly aggregated sequencing counts; systematic deviations indicate structural biases affecting spike-in representation during library preparation or sequencing. At the tertiary structure level—stabilized by base stacking, hydrogen bonding, and metal ion coordination—3D...
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Research: Multisite long-read sequencing reveals the early contributions of somatic structural variations to HBV-related hepatocellular carcinoma tumorigenesis
- Tianfu Zeng,
- Haotian Liao,
- Lin Xia,
- Siyao You,
- Yanqun Huang,
- Jiaxun Zhang,
- Yahui Liu,
- Xuyan Liu,
- and Dan Xie
Genome Res. April 2025 35: 671-685; Published in Advance March 4, 2025, doi:10.1101/gr.279617.124
...of HCC. Long-read RNA sequencing reveals that some HBV-induced SVs impact cancer-associated genes, with TRAs being capable of inducing the formation of fusion genes. These findings enhance our understanding of somatic SVs in HCC and their role in early tumorigenesis.As the most prevalent form of primary...
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Review: A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest
- Andrew D. Bates,
- Dawid Grzela,
- Maciej Studzian,
- Louise Brennan,
- Moli Williams,
- Conor Fawcett,
- Beth Hammond,
- Manreen Grewal,
- Marcin Ratajewski,
- Lukasz Pulaski,
- and Urszula L. McClurg
Genome Res. March 2026 36: 433-459; Published in Advance February 17, 2026, doi:10.1101/gr.281154.125
...).Beyond biological relevance, it is also important to distinguish between methods that study the steady state of the cell versus those that introduce experimental perturbations for comparative analysis. Some techniques rely on genetic modifications to reveal functional differences. Gain-of-function approaches...
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Research: Transcriptomic landscape of transposable elements reveals LTR7-PLAAT4 as a potential oncogene and therapeutic target in pancreatic adenocarcinoma
- Meilong Shi,
- Chuanqi Teng,
- Shan Zhang,
- Xiaobo He,
- Lingyun Xu,
- Fengxian Han,
- Rongqi Wen,
- Ganjun Yu,
- Jingwen Liu,
- Yang Feng,
- Yanfeng Wu,
- Yan Ren,
- Gang Jin,
- and Jing Li
Genome Res. February 2026 36: 275-290; Published in Advance January 8, 2026, doi:10.1101/gr.280528.125
...@smmu.edu.cn, ljing@smmu.edu.cnAbstractEukaryotic s contain numerous transposable elements (TEs), whose dysregulation threatens stability and may contribute to cancer. Pancreatic adenocarcinoma (PAAD) is among the deadliest cancers, marked by abundant stroma that obscures tumor-specific molecular signals...
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Method: Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution
- Qian Qin,
- Victoria Popic,
- Kirsty Wienand,
- Houlin Yu,
- Emily White,
- Akanksha Khorgade,
- Asa Shin,
- Christophe Georgescu,
- Catarina D. Campbell,
- Arthur Dondi,
- Niko Beerenwinkel,
- Francisca Vazquez,
- Aziz M. Al'Khafaji,
- and Brian J. Haas
Genome Res. April 2025 35: 967-986; Published in Advance March 14, 2025, doi:10.1101/gr.279200.124
...rigorous characterization of this tumor sample that further leveraged somatic mutations and copy number variations revealed tumor heterogeneity consisting of two subclones with the SMG7::CH507-513H4.1 fusion as one of the defining subclonal characteristics (Dondi et al. 2025). Fusion NTN1::CDRT15P2...
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Research: Closing the gaps, and improving somatic structural variant analysis and benchmarking using CHM13-T2T
- Luis F. Paulin,
- Jeremy Fan,
- Kieran O'Neill,
- Erin Pleasance,
- Vanessa L. Porter,
- Steven J.M. Jones,
- and Fritz J. Sedlazeck
Genome Res. April 2025 35: 621-631; Published in Advance March 17, 2025, doi:10.1101/gr.279352.124
...), generation of oncogenic fusion genes (e.g., BCR-ABL [Druker et al. 2001]), and silencing of tumor suppressor genes (e.g., TP53 [Hernández Borrero and El-Deiry 2021]). Accurate detection of somatic SVs and characterization of their functional effects is thus critical for appropriate cancer diagnosis...
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Research: Transcriptome-wide systematic search does not detect A-to-I RNA editing in cis-antisense RNA duplexes
- Zohar Rosenwasser,
- Roni Cohen-Fultheim,
- Ofir Shliefer,
- Erez Y. Levanon,
- and Eli Eisenberg
Genome Res. March 12, 2026 gr.280820.125; Published in Advance March 12, 2026, doi:10.1101/gr.280820.125
...’s role in preventing inappropriate immune activation. In this study, we systematically investigate whether intermolecular pairing of cis-NATs is a prevalent source of ADAR editing substrates in the human transcriptome. Specifically, we aim to determine how common editing is in regions where both strands...
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Research: Fusion, fission, and scrambling of the bilaterian genome in Bryozoa
- Thomas D. Lewin,
- Isabel Jiah-Yih Liao,
- Mu-En Chen,
- John D.D. Bishop,
- Peter W.H. Holland,
- and Yi-Jyun Luo
Genome Res. January 2025 35: 78-92; Published in Advance January 6, 2025, doi:10.1101/gr.279636.124
.... maximus, and L. longissimus exhibit high levels of similarity, having largely preserved the bilaterian ALGs (Fig. 3; Supplemental Fig. S6; Supplemental Table S8). Our analysis revealed that P. maximus and L. longissimus share four fusion events that have also been recorded in annelids and brachiopods (J2...
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Research: Pangenome analysis reveals families of ubiquitin-ligase adaptors as key genomic divergence drivers that lead to hybrid incompatibility
- Dongying Xie,
- Pohao Ye,
- Yiming Ma,
- and Zhongying Zhao
Genome Res. March 2026 36: 506-521; Published in Advance February 17, 2026, doi:10.1101/gr.280885.125
...Pan analysis reveals families of ubiquitin-ligase adaptors as key genomic divergence drivers that lead to hybrid incompatibility Dongying Xie1,2,3, Pohao Ye1,3, Yiming Ma1 and Zhongying Zhao1 1Department of Biology, Hong Kong Baptist University, Hong Kong SAR, China; 2Institute for Research...

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