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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
.... HOPS: a quantitative score reveals pervasive horizontal pleiotropy in human genetic variation is driven by extreme polygenicity of human traits and diseases. Genome Biol 20: 222. doi:10.1186/s13059-019-1844-7 ↵Jorjani H, Klei L, Emanuelson U. 2003. A simple method for weighted bending of genetic (co...
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Method: Genome-wide maps of CPD deamination in yeast reveal the impact of DNA sequence context and nucleosome architecture on cytosine deamination rates
- Marian F. Laughery,
- Bastian Stark,
- Benjamin Morledge-Hampton,
- Steven A. Roberts,
- and John J. Wyrick
Genome Res. January 2026 36: 183-196; Published in Advance December 9, 2025, doi:10.1101/gr.280384.124
...or water molecule on the C4 position of the cytosine base (Lemaire and Ruzsicska 1993; Uddin et al. 2014). Extensive biochemical analyses of 5-methylcytosine (5mC)-containing CPDs with variable flanking bases in vitro has revealed that deamination occurs fastest in cytosines with neighboring guanine bases...
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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
...of research to advance the study of archaic introgression.Prior to high-throughput sequencing, whether archaic humans (e.g., Neanderthals and Denisovans) contributed to the modern human gene pool was hotly debated (Stringer and Andrews 1988; Wolpoff et al. 1994; Stringer 2022). Early analyses of mitochondrial...
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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
...impacts and evolutionary patterns over time remain elusive in humans owing to the technical and ethical complexities of functional studies. Integrating gene age dating with Mendelian disease phenotyping, we reveal a gradual rise in disease gene proportion as gene age increases. Logistic regression...
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Research: Stable genome structures in living fossil fishes
- Cheng Wang,
- Chase D. Brownstein,
- Wenjun Chen,
- Zufa Ding,
- Dan Yu,
- Yu Deng,
- Chenguang Feng,
- Thomas J. Near,
- Shunping He,
- and Liandong Yang
Genome Res. February 2026 36: 318-329; Published in Advance January 13, 2026, doi:10.1101/gr.280800.125
.... Our analyses suggest that the genomic stability of gars, which may explain the ability of deeply divergent gar species to hybridize and has contributed to their higher structural similarity to tetrapod s than those of the far more closely related teleost fishes, may result from very low rates...
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Research: Widespread specific intron retention events in nuclear RNA complexes identified by sedimentation analysis of pluripotent cellular extracts
- Isabela T. Pereira,
- Izabela Mamede,
- Paulo P. Amaral,
- Gloria R. Franco,
- and John L. Rinn
Genome Res. October 2025 35: 2189-2198; Published in Advance August 26, 2025, doi:10.1101/gr.280431.125
...predominantly nuclear, metabolically stable, and they were not the major splice isoforms, but instead they were mostly retained-intron isoforms, each containing a specific retained intron, and this intron retention phenomenon is conserved in humans and mice. Collectively, our study reveals a widespread...
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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
...@cs.duke.eduAbstractEpigenetic mechanisms contribute to gene regulation by altering chromatin accessibility through changes in transcription factor (TF) and nucleosome occupancy across the . Despite numerous studies focusing on changes in gene expression, the intricate chromatin-mediated regulatory code remains largely uncharted...
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Research: Aberrant PRDM9 expression impacts the pan-cancer genomic landscape
- Armande Ang Houle,
- Heather Gibling,
- Fabien C. Lamaze,
- Hilary A. Edgington,
- David Soave,
- Marie-Julie Fave,
- Mawusse Agbessi,
- Vanessa Bruat,
- Lincoln D. Stein,
- and Philip Awadalla
Genome Res. November 2018 28: 1611-1620; Published in Advance October 19, 2018, doi:10.1101/gr.231696.117
...of understanding underlying causes of genomic instability.Here, we describe aberrant expression of PRDM9 among human tumors in vivo in 32 different cancer types (from n = 1879 patients) from the Pan-Cancer Analysis of Whole Genomes Project (PCAWG) and The Cancer Genome Atlas (TCGA) and assess the impact...
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Research: Genotype imputation from low-coverage data for medical and population genetic analyses
- Simone Andrea Biagini,
- Sara Becelaere,
- Mio Aerden,
- Tatjana Jatsenko,
- Laurens Hannes,
- Philip Van Damme,
- Jeroen Breckpot,
- Koenraad Devriendt,
- Bernard Thienpont,
- Joris Robert Vermeesch,
- Isabelle Cleynen,
- and Toomas Kivisild
Genome Res. September 2025 35: 1929-1941; Published in Advance July 22, 2025, doi:10.1101/gr.280175.124
....kivisild@kuleuven.beAbstractGenotype imputation from low-pass sequencing data presents unique opportunities for genomic analyses but comes with specific challenges. In this study, we explore the impact of quality filters on genetic ancestry and Polygenic Score (PGS) estimation after imputing 32,769 low-pass -wide sequences (LPS) from...
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Method: ML-MAGES enables multivariate genetic association analyses with genes and effect size shrinkage
- Xiran Liu,
- Lorin Crawford,
- and Sohini Ramachandran
Genome Res. December 2025 35: 2691-2700; Published in Advance November 19, 2025, doi:10.1101/gr.280440.125
..., or nonprioritized—among multiple traits based on their regularized effects. Clustering applied to our neural network shrinkage results also produces consistently higher precision and recall for distinguishing gene-level associations in simulations. We demonstrate the application of ML-MAGES on association analyses...
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