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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
...encompassing (1) differential gene expression analysis; (2) characterization of candidate cCREs; and (3) inference of cell type–specific, TF–target gene networks; and (4) integrative analyses linking peaks to genes and associating AD -wide association study (GWAS) loci with cCREs. This enabled prioritization...
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Method: Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease
- Tanner D. Jensen,
- Bohan Ni,
- Chloe M. Reuter,
- John E. Gorzynski,
- Sarah Fazal,
- Devon Bonner,
- Rachel A. Ungar,
- Pagé C. Goddard,
- Archana Raja,
- Euan A. Ashley,
- Jonathan A. Bernstein,
- Stephan Zuchner,
- Undiagnosed Diseases Network,
- Michael D. Greicius,
- Stephen B. Montgomery,
- Michael C. Schatz,
- Matthew T. Wheeler,
- and Alexis Battle
Genome Res. April 2025 35: 914-928; Published in Advance March 20, 2025, doi:10.1101/gr.279323.124
...causal for a rare neurodevelopmental disorder. Our observations demonstrate the promise of integrating long-read sequencing with gene expression toward improving the prioritization of functional SVs and TREs in rare disease patients.Long-read sequencing technology has improved in recent years in terms...
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Research: T2T-CHM13 improves read mapping and detection of clinically relevant genetic variation in the Swedish population
- Daniel Schmitz,
- Adam Ameur,
- and Åsa Johansson
Genome Res. November 2025 35: 2377-2388; Published in Advance September 16, 2025, doi:10.1101/gr.279320.124
...uniformTo investigate the coverage of genes in our sequencing data and assess potential improvements to detection of functionally relevant variants, we calculated the read depth for all nonoverlapping 500-bp bins in gene regions annotated by the T2T Consortium. Whereas we did not observe a change...
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Method: Analysis of coding gene expression from small RNA sequencing
- Aygun Azadova,
- Anthonia Ekperuoh,
- Greg N. Brooke,
- and Antonio Marco
Genome Res. March 2026 36: 611-618; Published in Advance February 10, 2026, doi:10.1101/gr.281364.125
...coding gene expression with qPCR-validated targets. Our findings demonstrate that quantifying mRNA fragments from sRNA-seq experiments provides a reliable approach to investigate microRNA–mRNA interactions when total RNA-seq is unavailable.The analysis of gene expression is a cornerstone of functional...
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Method: Tree-based differential testing using inferential uncertainty for RNA-seq
- Noor Pratap Singh,
- Euphy Y. Wu,
- Jason Fan,
- Michael I. Love,
- and Rob Patro
Genome Res. October 2025 35: 2326-2338; Published in Advance August 21, 2025, doi:10.1101/gr.279981.124
...-aware differential transcript/gene expression methods. Our method detects inner nodes that show a strong signal for differential expression, which would have been overlooked when analyzing the transcripts alone.RNA-seq has become the de facto technology for measuring the expression profiles of different genomic...
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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
...are usually lost over short evolutionary timescales, but they can be retained through three primary mechanisms: conservation of wild-type function, in which duplicates alter gene dosage or provide redundancy; subfunctionalization, in which ancestral function is partitioned across copies...
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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
...-related pathways, notably in oligodendrocytes at late aging stages. Integration with five public PD single-cell RNA-seq data sets highlights 85 genes consistently differentially expressed with aging and PD. Key genes such asHsp90aa1 andHsp90ab1 are upregulated at late aging stages in oligodendrocytes, microglia...
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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
...that the “circadian rhythm” pathway is a key signaling pathway highly relevant to the gene functions of A549 cells (Xiang et al. 2018, Sun et al. 2024). Similarly, as shown in Supplemental Figure S4, the GO enrichment analysis of the specific gene sets in cluster 0 reveals additional functional terms...
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Method: Robust and efficient annotation of cell states through gene signature scoring
- Laure Ciernik,
- Agnieszka Kraft,
- Florian Barkmann,
- Josephine Yates,
- and Valentina Boeva
Genome Res. March 2026 36: 630-644; Published in Advance February 18, 2026, doi:10.1101/gr.280926.125
...score stability and cross-signature comparability, achieving cell-state annotation accuracy comparable to supervised methods. We demonstrate the practical utility of ANS by developing and validating a gene signature to differentiate cancer-associated fibroblasts from malignant cells undergoing...
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Research: Transposon wave remodeled the epigenomic landscape in the rapid evolution of X-Chromosome dosage compensation
- David C.H. Metzger,
- Imogen Porter,
- Brendan Mobley,
- Benjamin A. Sandkam,
- Lydia J.M. Fong,
- Andrew P. Anderson,
- and Judith E. Mank
Genome Res. November 2023 33: 1917-1931; Published in Advance November 21, 2023, doi:10.1101/gr.278127.123
..., suggesting that these hypomethylated regions do not function on a gene-by-gene basis to up-regulate genes on the male X. Taken together, these data suggest a putative dosage compensation system that involves the regulation of YY1 DNA-binding affinity via sex-specific DNA methylation. The DNA methylation...

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