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Mini-Review: A Hitchhiker's Guide to long-read genomic analysis
- Medhat Mahmoud,
- Daniel P. Agustinho,
- and Fritz J. Sedlazeck
Genome Res. April 2025 35: 545-558; doi:10.1101/gr.279975.124
...-seq (including epigenetic modifications). We recommend that readers interested in more details about the two platforms read the review by Logsdon et al. (2020).Both PacBio and ONT excel in resolving repetitive elements and identifying complex genomic variants, including structural variants (SVs), which have...
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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
...), and similar results were reported for the mouse(Kiyosawa et al. 2003), Drosophila(Misra et al. 2002), Arabidopsis(Meyers et al. 2004; Wang et al. 2014), and rice s(Osato et al. 2003). In addition, many long intergenic non-coding RNAs (lincRNAs) have been identified as antisense transcripts, further...
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Research: Genome-wide nucleosome and transcription factor responses to genetic perturbations reveal chromatin-mediated mechanisms of transcriptional regulation
- Kevin Moyung,
- Yulong Li,
- Heather K. MacAlpine,
- Alexander J. Hartemink,
- and David M. MacAlpine
Genome Res. January 2026 36: 115-128; Published in Advance December 9, 2025, doi:10.1101/gr.279637.124
...factor-specific antibodies; the exact mechanisms of the interplay of all TFs and nucleosomes have yet to be explored with respect to transcription.To address these challenges, here we develop a systematic, genetic approach to simultaneously profile nucleosome and TF changes in response to single-gene...
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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
...analysis, providing comprehensive exploration of gene expression across diverse biological contexts. However, RNA-seq data are susceptible to various biases that can significantly compromise the accuracy and reliability of transcript quantification. This study investigates the influence of high...
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Method: A scalable computational framework for predicting gene expression from candidate cis-regulatory elements
- Qinhu Zhang,
- Siguo Wang,
- Zhipeng Li,
- Wenzheng Bao,
- Wenjian Liu,
- and De-Shuang Huang
Genome Res. February 2026 36: 361-374; Published in Advance January 16, 2026, doi:10.1101/gr.281219.125
...to improve the performance of identifying distal cCRE–gene interactions by incorporating chromatin loops into the ScPGE model.In fact, several key hyperparameters—such as DNA sequence length, nonredundant TF motifs, and cell-specific cCREs—have yet to be systematically explored. Based on the GM12878 and K562...
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Resource: Single-nucleus multiomic profiling of the aging mouse substantia nigra reveals conserved gene alterations linked to Parkinson's disease
- Kangli Wang,
- Weikun Xia,
- Yingli Gu,
- Songpeng Zu,
- Qian Yang,
- Maria Luisa Amaral,
- Yaozhi Wang,
- Allen Wang,
- Xiang-Dong Fu,
- William C. Mobley,
- and Bing Ren
Genome Res. March 4, 2026 ; Published in Advance March 4, 2026, doi:10.1101/gr.281113.125
...to further explore the regulatory networks and identify putative enhancers and potential transcription factors involved in these pathways. We identified 80 putative enhancers related to these genes, and motif enrichment analysis revealed that transcription factors such as CTCF, BORIS, TCF3, and PRDM15 may...
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Method: Recovering gene regulatory networks in single-cell multi-omics data with PRISM-GRN
- Wenhao Zhang,
- Lan Cao,
- Xiaoxuan Gu,
- Yongyu Long,
- and Ying Wang
Genome Res. January 2026 36: 142-158; Published in Advance October 9, 2025, doi:10.1101/gr.280757.125
..., and interpretable exploration of causal GRNs with prior knowledge and multi-omics data.Gene regulatory networks (GRNs), which encapsulate the complex interactions among transcription factors (TFs), target genes, and various regulatory elements, constitute the core machinery of gene regulation (Levine and Davidson...
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Research: Integrating genetic variation with deep learning provides context for variants impacting transcription factor binding during embryogenesis
- Olga M. Sigalova,
- Mattia Forneris,
- Frosina Stojanovska,
- Bingqing Zhao,
- Rebecca R. Viales,
- Adam Rabinowitz,
- Fayrouz Hammal,
- Benoît Ballester,
- Judith B. Zaugg,
- and Eileen E.M. Furlong
Genome Res. May 2025 35: 1138-1153; Published in Advance April 15, 2025, doi:10.1101/gr.279652.124
...variants occur in the noncoding (Edwards et al. 2013; Buniello et al. 2019) and likely affect gene regulation (Claringbould and Zaugg 2021). One mechanism by which mutations impact transcriptional programs is through the disruption of transcription factor (TF) binding sites within regulatory elements...
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Method: Biosurfer for systematic tracking of regulatory mechanisms leading to protein isoform diversity
- Mayank Murali,
- Jamie Saquing,
- Senbao Lu,
- Ziyang Gao,
- Emily F. Watts,
- Ben Jordan,
- Zachary Peters Wakefield,
- Ana Fiszbein,
- David R. Cooper,
- Peter J. Castaldi,
- Dmitry Korkin,
- and Gloria M. Sheynkman
Genome Res. April 2025 35: 1012-1024; Published in Advance March 14, 2025, doi:10.1101/gr.279317.124
...isoforms using BiosurferThe principal and alternative isoforms were defined using the APPRIS annotation of genes (Rodriguez et al. 2013). First, the set of APPRIS isoforms is identified for each gene from the input data (GENCODE v42, basic annotation [Frankish et al. 2021]) by extracting the key transcript...
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Method: Recalibrating differential gene expression by genetic dosage variance prioritizes functionally relevant genes
- Philipp Rentzsch,
- Aaron Kollotzek,
- Kaushik Ram Ganapathy,
- Pejman Mohammadi,
- and Tuuli Lappalainen
Genome Res. October 2025 35: 2316-2325; Published in Advance September 17, 2025, doi:10.1101/gr.280360.124
...that recalibration produces robust patterns for gene sets, users are encouraged to interpret results from individual genes with some caution. Nevertheless, our results indicate that our approach has the potential to identify phenotypic drivers, guiding downstream analyses toward genes and processes...
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