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Method: Minimizing reference bias with an imputed personalized reference
- Kavya Vaddadi,
- Mao-Jan Lin,
- Sina Majidian,
- Taher Mun,
- and Ben Langmead
Genome Res. March 5, 2026 gr.280989.125; Published in Advance March 5, 2026, doi:10.1101/gr.280989.125
...methods is to reduce the “reference bias” that results when aligning reads to a single reference (Lin et al. 2024). Bias occurs when reads containing non-reference alleles fail to align to their true point of origin, leading to inaccurate results for analyses concerned with hypervariable regions (Brandt...
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Research: Cell-type- and chromosome-specific chromatin landscapes and DNA replication programs of Drosophila testis tumor stem cell–like cells
- Jennifer A. Urban,
- Daniel Ringwalt,
- John M. Urban,
- Wingel Xue,
- Ryan Gleason,
- Keji Zhao,
- and Xin Chen
Genome Res. January 2026 36: 83-101; Published in Advance December 10, 2025, doi:10.1101/gr.280809.125
..., enabling a detailed analysis of their transcriptome, chromatin landscapes, and replication timing dynamics. This approach uncovered previously unrecognized chromosome-specific differences in chromatin regulation between GSCs and CySCs, shedding new light on the molecular mechanisms regulating stem...
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Research: Molecular and genetic landscapes of retina and brain microglia in neurodegenerative diseases
- Khang Ma and
- Rinki Ratnapriya
Genome Res. October 2025 35: 2143-2157; Published in Advance August 26, 2025, doi:10.1101/gr.280554.125
...of the disease-relevant tissues and cell types, and exert their effects through gene expression regulation (Albert and Kruglyak 2015; Ratnapriya et al. 2019, 2025). In this study, we analyzed the transcriptomes and epis of microglia from the retina and brain across multiple donors, compared their molecular...
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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
..., hinging on the precise binding of transcription factors (TFs) and cofactors to gene regulatory elements such as promoters and enhancers. Although it is relatively routine to profile -wide DNA binding landscapes of proteins, identifying the specific proteins that bind to, and regulate the transcription of...
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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
...microenvironment on this heterogeneous mutation landscape can lead to the development of treatment-resistant subclones and influence the choice of therapy (Mumenthaler et al. 2015; Zhang et al. 2017; Fisk et al. 2022). Treatment regimens further influence clonal selection and complicate decisions regarding...
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Research: Ancient dog introgression into the Iberian wolf genome may have facilitated adaptation to human-dominated landscapes
- Diana Lobo,
- Hernán E. Morales,
- Cock Van Oosterhout,
- José Vicente López-Bao,
- Pedro Silva,
- Luis Llaneza,
- Carolina Pacheco,
- Diana Castro,
- Germán Hernández-Alonso,
- George Pacheco,
- John Archer,
- M. Thomas P. Gilbert,
- Nuno Ferrand,
- and Raquel Godinho
Genome Res. March 2025 35: 432-445; Published in Advance February 14, 2025, doi:10.1101/gr.279093.124
...us to exclude the possibility of positive selection. Variables such as historical population size, the timing of selection onset, genetic drift, and past genetic structure within the Iberian wolf population could influence the rate of allele fixation under positive selection, potentially explaining...
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Research: Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects of SF3B1 mutations
- Alicja Pacholewska,
- Matthias Lienhard,
- Mirko Brüggemann,
- Heike Hänel,
- Lorina Bilalli,
- Anja Königs,
- Felix Heß,
- Kerstin Becker,
- Karl Köhrer,
- Jesko Kaiser,
- Holger Gohlke,
- Norbert Gattermann,
- Michael Hallek,
- Carmen D. Herling,
- Julian König,
- Christina Grimm,
- Ralf Herwig,
- Kathi Zarnack,
- and Michal R. Schweiger
Genome Res. November 2024 34: 1832-1848; Published in Advance September 13, 2024, doi:10.1101/gr.279327.124
...(LRTS) and combined complementary data derived from MDS and CLL patients with isogenic cell lines.ResultsLong-read RNA-seq expands patient transcriptome landscapes in divergent biological contextsTo investigate the effect of SF3B1 mutations on splicing, we characterized the transcriptomes of three data...
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Research: Strong bias in long-read sequencing prevents assembly of Drosophila melanogaster Y-linked genes
- A. Bernardo Carvalho,
- Bernard Y. Kim,
- and Fabiana Uno
Genome Res. January 2026 36: 71-82; Published in Advance October 1, 2025, doi:10.1101/gr.280604.125
...), using the shallower and equally biased PacBio CLR data set from Kim et al. (2014), had to manually fill the gaps in Y-linked genes by integrating CDS sequences from FlyBase (Larkin et al. 2021).The bias primarily affects read initiation but also impairs read extension and basecalling, with read...
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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
...-regulators and cell type–specific regulatory landscapes of GWAS loci across AD progression by integrative analysis. (A) Top enriched TF motifs for each cell type. The color scale represents −log10 (adjusted P-value) of the normalized enrichment score. (B) Tn5 bias-corrected TF footprinting for SPI1. (C) Positive TF...
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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 gr.281113.125; Published in Advance March 4, 2026, doi:10.1101/gr.281113.125
...the model for cell subclasses with at least 100 nuclei 546 in total and 10 nuclei in any biological replicate of each age stage, focusing on genes expressed 547 in at least 10 nuclei. To avoid sex bias, we only assessed genes on autosomes. The p-value 548 tested whether the effect of age was significantly...
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