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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
...and identify therapeutic opportunities. Here, we develop a cell type–specific regulatory atlas of the human middle temporal gyrus via leveraging single-nucleus RNA-seq (1,197,032 nuclei) and ATAC-seq (740,875 nuclei) data sets from 84 donors across four stages of AD neuropathological change (ADNC). We observe...
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Method: High-fidelity bidirectional translation between single-cell transcriptomes and DNA methylomes with scBOND
- Kehan Lang,
- Chenyang Jia,
- Siyu Li,
- Yi Guo,
- Dingjun Hu,
- and Shengquan Chen
Genome Res. April 2026 36: 769-784; Published in Advance March 26, 2026, doi:10.1101/gr.281350.125
...cells (ExEs), and notochord (Fig. 2B). These populations are known to co-occur during early embryonic development and engage in complex signaling interactions (Shahbazi et al. 2019; Xu et al. 2023). However, because of their close developmental origins, they are notoriously difficult to distinguish...
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Review: The superpowers of imprinting control regions
- Bertille Montibus,
- Franck Court,
- and Philippe Arnaud
Genome Res. January 2026 36: 1-19; Published in Advance December 10, 2025, doi:10.1101/gr.281215.125
...Bertille Montibus, Franck Court and Philippe Arnaud Genetics, Reproduction and Development Institute (iGReD), CNRS, INSERM, Université Clermont Auvergne, 63000 Clermont-Ferrand, France Corresponding author: philippe.arnaud@uca.frAbstractGenomic imprinting is a specialized mechanism...
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Method: Identification of the shortest species-specific oligonucleotide sequences
- Ioannis Mouratidis,
- Maxwell A. Konnaris,
- Nikol Chantzi,
- Candace S.Y. Chan,
- Michail Patsakis,
- Kimonas Provatas,
- Austin Montgomery,
- Fotis A. Baltoumas,
- Congzhou M. Sha,
- Manvita Mareboina,
- Georgios A. Pavlopoulos,
- Dionysios V. Chartoumpekis,
- and Ilias Georgakopoulos-Soares
Genome Res. February 2025 35: 279-295; Published in Advance January 2, 2025, doi:10.1101/gr.280070.124
...,076 organismal reference s, present in one and absent from every other examined . In the human , we find that the genomic loci of nucleic quasi-primes are most enriched for genes associated with brain development and cognitive function. In a single-cell case study focusing on the human primary motor cortex...
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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. April 2026 36: 849-864; Published in Advance March 4, 2026, doi:10.1101/gr.281113.125
...). Despite aging being the greatest risk factor for developing PD, the mechanisms by which aging promotes PD are not fully understood. High-resolution studies of cellular and molecular changes during aging could yield essential insights into the disease's pathophysiology.Recent advances in single...
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Method: Characterizing tandem repeat complexities across long-read sequencing platforms with TREAT and otter
- Niccoló Tesi,
- Alex Salazar,
- Yaran Zhang,
- Sven van der Lee,
- Marc Hulsman,
- Lydian Knoop,
- Sanduni Wijesekera,
- Jana Krizova,
- Anne-Fleur Schneider,
- Maartje Pennings,
- Kristel Sleegers,
- Erik-Jan Kamsteeg,
- Marcel Reinders,
- and Henne Holstege
Genome Res. November 2024 34: 1942-1953; Published in Advance October 15, 2024, doi:10.1101/gr.279351.124
...of 246 AD patients (mean age = 67.9 ± 9.8, 70% females) and N = 248 cognitively healthy centenarians (mean age = 101.2 ± 2.5, 70% females) that were sequenced with PacBio Sequel II instrument (Methods; Supplemental Fig. S15; Salazar et al. 2023). Across all 494 s, we observed a median coverage (HiFi data...
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Research: Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids
- Benjamin D. Umans and
- Yoav Gilad
Genome Res. August 2025 35: 1689-1700; Published in Advance June 2, 2025, doi:10.1101/gr.280219.124
...(Wehby 2013; Salmaso et al. 2014; Lavie 2015; Prabhakar et al. 2020; Erickson et al. 2021). Hypoxic exposure has profound effects on cognitive function and white matter integrity and increases the risk for neurodegeneration and psychiatric disorders (Cannon et al. 2002; Thomas et al. 2005; Halbower et al...
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Research: Assessing the readiness of Oxford Nanopore sequencing for clinical genomics applications
- Judith Arres,
- Santosh Elavalli,
- Shalini Behl,
- Daniel Matias Sanchez,
- Ayesha Al Ali,
- Abdelrahman Ahmed Yehia Abdelaziz Saad,
- Azza Attia,
- Cyla Minas,
- Sharika Pariyachery,
- Shariq Ahmed,
- Fatmah Aldhuhoori,
- Nitu Thulasidharan,
- Gurunath Katagi,
- Omar Soliman,
- Shilp Purohit,
- Vinay Kusuma,
- Raony Cardenas,
- Thyago Cardoso,
- Luis F. Paulin,
- Philippe Sanio,
- Joseph Mafofo,
- Haiguo Wu,
- Val Zvereff,
- Albarah El-Khani,
- Fahed Al Marzooqi,
- Tiago R. Magalhães,
- Fritz J. Sedlazeck,
- and Javier Quilez
Genome Res. March 2026 36: 460-471; Published in Advance February 11, 2026, doi:10.1101/gr.280134.124
.... 2019). Together, these developments demonstrate the increasing applicability of LRS technologies in clinical genomics.ONT has evolved from early versions with >20% error rates to a robust production platform (Ni et al. 2023; Sanderson et al. 2024), supported by continuous improvements in chemistry...
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Method: Multisample motif discovery and visualization for tandem repeats
- Yaran Zhang,
- Marc Hulsman,
- Alex Salazar,
- Niccolò Tesi,
- Lydian Knoop,
- Sven van der Lee,
- Sanduni Wijesekera,
- Jana Krizova,
- Erik-Jan Kamsteeg,
- and Henne Holstege
Genome Res. April 2025 35: 850-862; Published in Advance November 13, 2024, doi:10.1101/gr.279278.124
.... These findings emphasize the importance of considering both repeat length and motif organization in TR genotyping.With new sequencing technologies emerging that combine longer read length and higher accuracy, it is now possible to deeply characterize TRs. As such, multiple methods have been developed to genotype...
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Research: Identification and validation of supervariants reveal novel loci associated with human white matter microstructure
- Shiying Wang,
- Ting Li,
- Bingxin Zhao,
- Wei Dai,
- Yisha Yao,
- Cai Li,
- Tengfei Li,
- Hongtu Zhu,
- and Heping Zhang
Genome Res. January 2024 34: 20-33; Published in Advance December 12, 2023, doi:10.1101/gr.277905.123
...,842) data for discovery and internal validation, and UK Biobank White but non-British (n = 1927) data, Europeans from the Adolescent Brain Cognitive Development study (n = 4399) data, and Europeans from the Human Connectome Project (n = 319) data for external validation. We identify 23 novel loci...
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