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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
...for detecting molecular variation that is not tolerated by natural selection.In this study, we have developed a novel calibration method to measure DE by scaling standard expression changes with the population genetic dosage variation estimate VG, a metric which we had previously introduced (Mohammadi et al...
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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
..., a fundamental component of dosage compensation mechanisms studied to date is the up-regulation of genes on the X Chromosome to compensate for gene dosage imbalances in the heterogametic sex (Deng et al. 2011; Larsson et al. 2019; Lentini et al. 2022). In eutherian mammals, up-regulation of genes on the single...
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Research: Extensive protein dosage compensation in aneuploid human cancers
- Klaske M. Schukken and
- Jason M. Sheltzer
Genome Res. July 2022 32: 1254-1270; Published in Advance June 14, 2022, doi:10.1101/gr.276378.121
...copy number changes influence the cancer proteome, we conducted an analysis of hundreds of human cancer cell lines and tumors with matched copy number, RNA expression, and protein expression data. We found that a majority of proteins show dosage compensation and fail to change by the degree expected...
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Method: Structure-optimized sgRNA selection with PlatinumCRISPr for efficient Cas9 generation of knockouts
- Irmgard U. Haussmann,
- Thomas C. Dix,
- David W.J. McQuarrie,
- Veronica Dezi,
- Abdullah I. Hans,
- Roland Arnold,
- and Matthias Soller
Genome Res. December 2024 34: 2279-2292; Published in Advance December 3, 2024, doi:10.1101/gr.279479.124
...% for more than half of randomly selected sgRNA sequences in human cell culture screens or model organisms. We used in vitro assays to determine intrinsic molecular parameters for maximal sgRNA activity including correct folding of sgRNAs and Cas9 structural information. From the comparison of over 10 data...
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Research: Evolutionarily new genes in humans with disease phenotypes reveal functional enrichment patterns shaped by adaptive innovation and sexual selection
- Jian-Hai Chen,
- Patrick Landback,
- Deanna Arsala,
- Alexander Guzzetta,
- Shengqian Xia,
- Jared Atlas,
- Dylan Sosa,
- Yong E. Zhang,
- Jingqiu Cheng,
- Bairong Shen,
- and Manyuan Long
Genome Res. March 2025 35: 379-392; Published in Advance February 14, 2025, doi:10.1101/gr.279498.124
...million years). Despite this stable pace, we observe distinct patterns in phenotypic enrichment, pleiotropy, and selective pressures across gene ages. Young genes show significant enrichment in diseases related to the male reproductive system, indicating strong sexual selection. Young genes also exhibit...
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Research: Independent expansion, selection, and hypervariability of the TBC1D3 gene family in humans
- Xavi Guitart,
- David Porubsky,
- DongAhn Yoo,
- Max L. Dougherty,
- Philip C. Dishuck,
- Katherine M. Munson,
- Alexandra P. Lewis,
- Kendra Hoekzema,
- Jordan Knuth,
- Stephen Chang,
- Tomi Pastinen,
- and Evan E. Eichler
Genome Res. November 2024 34: 1798-1810; Published in Advance August 6, 2024, doi:10.1101/gr.279299.124
...at this locus, differing by as many as 20 copies and ∼1 Mbp in length depending on haplotypes. We also show evidence of positive selection, as well as a significant change in the predicted human TBC1D3 protein sequence. Last, we find that, despite multiple duplications, human TBC1D3 expression is limited...
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Method: Memory-bound k-mer selection for large and evolutionarily diverse reference libraries
- Ali Osman Berk Şapcı and
- Siavash Mirarab
Genome Res. September 2024 34: 1455-1467; Published in Advance August 29, 2024, doi:10.1101/gr.279339.124
...minimizers and finding taxon-specific k-mers. However, we contend that these strategies are inadequate, especially when reference sets are taxonomically imbalanced, as are most microbial libraries. In this paper, we explore approaches for selecting a fixed-size subset of k-mers present in an ultra-large data...
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Method: Label-free selection of marker genes in single-cell and spatial transcriptomics with geneCover
- An Wang,
- Stephanie Hicks,
- Donald Geman,
- and Laurent Younes
Genome Res. December 2025 35: 2744-2755; Published in Advance November 12, 2025, doi:10.1101/gr.280539.125
...for Imaging Science, Johns Hopkins University, Baltimore, Maryland 21218, USA Corresponding author: awang87@jhu.eduAbstractThe selection of marker gene panels is critical for capturing the cellular and spatial heterogeneity in the expanding atlases of single-cell RNA sequencing (scRNA-seq) and spatial...
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Method: Highly accurate reference and method selection for universal cross–data set cell type annotation with CAMUS
- Qunlun Shen,
- Shuqin Zhang,
- and Shihua Zhang
Genome Res. November 2025 35: 2527-2538; Published in Advance October 1, 2025, doi:10.1101/gr.280821.125
...Highly accurate reference and method selection for universal cross–data set cell type annotation with CAMUS Qunlun Shen1,2, Shuqin Zhang1,3 and Shihua Zhang2,4,5 1School of Mathematical Sciences, Fudan University, Shanghai 200433, China; 2State Key Laboratory of Mathematical Sciences, Academy...
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Research: Recruitment of histone modifications to assist mRNA dosage maintenance after degeneration of cytosine DNA methylation during animal evolution
- Andrew Ying-Fei Chang and
- Ben-Yang Liao
Genome Res. September 2017 27: 1513-1524; Published in Advance July 18, 2017, doi:10.1101/gr.221739.117
...is unrelated to the process of gene dosage control. Our results based on H3K27me3 indicate that differential mechanisms have been employed over the evolution of Drosophila to create regulatory/functional divergence and to cope with increases in mRNA and protein that occur after gene duplication events. Various...

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