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Review: Recent advances in methods to characterize archaic introgression in modern humans
- David Peede,
- Mayra M. Bañuelos,
- Jazeps Medina Tretmanis,
- Miriam Miyagi,
- and Emilia Huerta-Sánchez
Genome Res. February 2026 36: 239-256; Published in Advance January 16, 2026, doi:10.1101/gr.278993.124
...a posterior probability threshold, reflecting the frequency of introgression in the sampled ARGs. Applying ARGweaver-D to modern and archaic s, Hubisz et al. (2020) estimated that 3%–7% of the Neanderthal originated from an introgression event with early modern humans 200–300 kya. They also inferred that 1...
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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
...; Kim and Wysocka 2023).Early efforts to recover GRNs relied on experimental validation, such as chromatin immunoprecipitation followed by sequencing (ChIP-seq) (Park 2009). Although these approaches provide high-confidence data, they are costly, time-consuming, and limited in scale, making it difficult...
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Method: QuadST identifies cell–cell interaction–changed genes in spatially resolved transcriptomics data
- Xiaoyu Song,
- Yuqing Shang,
- Michelle E. Ehrlich,
- Panos Roussos,
- Guo-Cheng Yuan,
- and Pei Wang
Genome Res. August 2025 35: 1821-1831; Published in Advance June 23, 2025, doi:10.1101/gr.279859.124
...human diseases, such as cancer (Maffuid and Cao 2023) and neurodegenerative diseases (Szepesi et al. 2018). Spatially resolved transcriptomics (SRT) provides an invaluable avenue for understanding the cell–cell interactions, by allowing researchers to study the gene expression profiles of cells within...
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Method: Designing realistic regulatory DNA with autoregressive language models
- Avantika Lal,
- David Garfield,
- Tommaso Biancalani,
- and Gokcen Eraslan
Genome Res. September 2024 34: 1411-1420; Published in Advance September 25, 2024, doi:10.1101/gr.279142.124
..., low, or cell type–specific activity, using autoregressive language models in conjunction with supervised sequence-to-function models. We used our framework to design synthetic yeast promoters and cell type–specific human enhancers. We demonstrate that the synthetic CREs generated by our approach...
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Method: Partial alignment of multislice spatially resolved transcriptomics data
- Xinhao Liu,
- Ron Zeira,
- and Benjamin J. Raphael
Genome Res. July 2023 33: 1124-1132; Published in Advance August 8, 2023, doi:10.1101/gr.277670.123
...multiple slices can help recover this information and improve downstream expression analyses, but multislice alignment and integration remains a challenging task. Existing methods for integrating SRT data either do not use spatial information or assume that the morphology of the tissue is largely preserved...
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Research: Widespread natural selection on metabolite levels in humans
- Yanina Timasheva,
- Kaido Lepik,
- Orsolya Liska,
- Balázs Papp,
- and Zoltán Kutalik
Genome Res. August 2024 34: 1121-1129; Published in Advance August 16, 2024, doi:10.1101/gr.278756.123
...Security, Institute of Biochemistry, Biological Research Centre, HUN-REN, H-6726 Szeged, Hungary Corresponding author: zoltan.kutalik@unil.chAbstractNatural selection acts ubiquitously on complex human traits, predominantly constraining the occurrence of extreme phenotypes (stabilizing selection...
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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
...copies of TBC1D3 paralogs, and we evaluated each contig for gaps and contiguity (see Assembly validation section below). Most human s were originally assembled using Hifiasm (version 0.15.2), but TBC1D3-containing contigs that failed QC were reassembled with Verkko (versions 1.0, 1.1, 1.2, and 1.4) using...
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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
...ancient) nodes to modern humans (br0–br6) (Fig. 1A). We observed an increase in the proportion of disease genes over evolutionary time (Supplemental Fig. S1; Fig. 1A,C), suggesting that gene age impacts disease susceptibility, a trend qualitatively consistent with earlier studies (Domazet-Lošo and Tautz...
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Method: Characterizing spatial gene expression heterogeneity in spatially resolved single-cell transcriptomic data with nonuniform cellular densities
- Brendan F. Miller,
- Dhananjay Bambah-Mukku,
- Catherine Dulac,
- Xiaowei Zhuang,
- and Jean Fan
Genome Res. October 2021 31: 1843-1855; Published in Advance May 25, 2021, doi:10.1101/gr.271288.120
...further require adjacent cells to be within a certain spatial distance in space to accommodate realistic length scales of cellular interactions. This neighborhood representation of cells accommodates varying neighborhood sizes and distances between cells and thus can characterize cell types and tissues...
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Method: A model-based constrained deep learning clustering approach for spatially resolved single-cell data
- Xiang Lin,
- Le Gao,
- Nathan Whitener,
- Ashley Ahmed,
- and Zhi Wei
Genome Res. October 2022 32: 1906-1917; Published in Advance October 5, 2022, doi:10.1101/gr.276477.121
...tissue areas and allows for the construction of data-driven reference atlases of human tissue. The second type includes the sequencing-based approaches, such as 10x Visium and Slide-seq. A joint robust dissection of scRNA-seq data with spatially resolved single-cell transcriptomics captures a detailed...

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