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Review: A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest
- Andrew D. Bates,
- Dawid Grzela,
- Maciej Studzian,
- Louise Brennan,
- Moli Williams,
- Conor Fawcett,
- Beth Hammond,
- Manreen Grewal,
- Marcin Ratajewski,
- Lukasz Pulaski,
- and Urszula L. McClurg
Genome Res. March 2026 36: 433-459; Published in Advance February 17, 2026, doi:10.1101/gr.281154.125
...looping and high-order chromatin structure (Panigrahi and O'Malley 2021; Karr et al. 2022; Chen et al. 2024b). Furthermore, the DNA interactome at a particular gene locus is controlled by the availability of the transcription machinery, its correct localization, transcriptional complex formation...
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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
...to profile the transcriptome at the cellular level, allowing for quantifying cell types and states, analyzing inter- and intrasample heterogeneity, discovering cell differentiation trajectories, and constructing gene regulatory networks (Zhao et al. 2022). Interpretation of such data can be challenging owing...
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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
..., Hsp90ab1, Hsp90b1, and Cryab) and locomotory behavior (Aplp2, Selenop, and Sez6l2) and downregulation of those related to regulation of cell junction assembly (Clasp2, Ptk2, Srcin1, and Rap1a). The expression of these genes during aging mirrored patterns seen in PD, highlighting potential molecular...
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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
...that this approach will simplify the identification of disease-causing molecular processes and enhance the discovery of therapeutic targets.Since the advent of cDNA microarrays (Schena et al. 1995), differential gene expression profiling has been used to examine the characteristic gene regulatory changes...
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Review: Artificial intelligence and machine learning in cell-free-DNA-based diagnostics
- W.H. Adrian Tsui,
- Spencer C. Ding,
- Peiyong Jiang,
- and Y.M. Dennis Lo
Genome Res. January 2025 35: 1-19; doi:10.1101/gr.278413.123
..., such as in Illumina's VeriSeq NIPT solution v2 assay, and also for single gene disorder analysis. For the latter, relative mutation dosage (RMD) (Lun et al. 2008) and relative haplotype dosage (RHDO) (Lo et al. 2010) establish statistical thresholds for classifying fetal monogenic disorders from maternal plasma DNA...
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Research: Hydroxycarbamide effects on DNA methylation and gene expression in myeloproliferative neoplasms
- Stephania Contreras Castillo,
- Bertille Montibus,
- Azucena Rocha,
- Will Duke,
- Ferdinand von Meyenn,
- Donal McLornan,
- Claire Harrison,
- Ann Mullally,
- Reiner Schulz,
- and Rebecca J. Oakey
Genome Res. August 2021 31: 1381-1394; Published in Advance July 9, 2021, doi:10.1101/gr.270066.120
...in a murine MPN model. This study was replicated in MPN patients by profiling -wide gene expression and DNA methylation using patient blood samples collected longitudinally, before and following HC exposure. The effects of HC on the transcriptome were not only associated with cell cycle interruption but also...
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Resource: Discordant calls across genotype discovery approaches elucidate variants with systematic errors
- Elizabeth G. Atkinson,
- Mykyta Artomov,
- Alexander A. Loboda,
- Heidi L. Rehm,
- Daniel G. MacArthur,
- Konrad J. Karczewski,
- Benjamin M. Neale,
- and Mark J. Daly
Genome Res. May 30, 2023 ; Published in Advance May 30, 2023, doi:10.1101/gr.277908.123
...-throughput sequencing approaches in recovering coding DNA variation. Similarly, we performed this concordance analysis on the All of Us Research Program data set to compare AFs between WGS and microarray genotyping to quantify any similar effect arising between these genotype discovery approaches in primarily noncoding...
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RECOMB 2022 Special/Methods: Learning probabilistic protein–DNA recognition codes from DNA-binding specificities using structural mappings
- Joshua L. Wetzel,
- Kaiqian Zhang,
- and Mona Singh
Genome Res. September 2022 32: 1776-1786; Published in Advance September 19, 2022, doi:10.1101/gr.276606.122
...for understanding gene regulation. Although DNA-binding specificities for thousands of transcription factors (TFs) have been determined, the specific amino acid–base interactions comprising their structural interfaces are largely unknown. This lack of resolution hampers attempts to leverage these data in order...
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Method: A Bayesian framework to study tumor subclone–specific expression by combining bulk DNA and single-cell RNA sequencing data
- Yi Qiao,
- Xiaomeng Huang,
- Philip J. Moos,
- Jonathan M. Ahmann,
- Anthony D. Pomicter,
- Michael W. Deininger,
- John C. Byrd,
- Jennifer A. Woyach,
- Deborah M. Stephens,
- and Gabor T. Marth
Genome Res. January 2024 34: 94-105; Published in Advance January 9, 2024, doi:10.1101/gr.278234.123
...probabilistic framework that uses tumor subclonal structure inferred from bulk DNA sequencing data to determine the subclonal identity of cells from single-cell gene expression (scRNA-seq) measurements. Grouping together cells representing the same genetically defined tumor subclones allows comparison of gene...
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Resource: Multiscale network modeling reveals the gene regulatory landscape driving cancer prognosis in 32 cancer types
- Peng Xu and
- Bin Zhang
Genome Res. October 2023 33: 1806-1817; Published in Advance October 31, 2023, doi:10.1101/gr.278063.123
...of module-level DNA methylation and its impact on patient prognosis. We focused on 16 cancer types that had enough normal samples for comparative analysis with tumor samples. We identified 1517 and 1626 network modules significantly enriched for up-regulated and down-regulated differentially expressed genes...
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