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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
...these are experimental data that detected actual TF binding to a specific locus or site, this does not necessarily mean that the TF has an important function in GOI regulation, especially not in your favorite cell type/condition/treatment. However, this is probably the strongest hypothesis-generating tool available...
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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
...atlas provides a comprehensive resource for mechanistic understanding, target prioritization, and therapeutic hypothesis generation in AD and AD-related dementia if broadly applied.Alzheimer's disease (AD) is a complex, age-related neurodegenerative disorder and the leading cause of dementia worldwide...
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Method: Dissecting multilayer cell–cell communications with signaling feedback loops from spatial transcriptomics data
- Lulu Yan,
- Jinyu Cheng,
- Qing Nie,
- and Xiaoqiang Sun
Genome Res. June 2025 35: 1400-1414; Published in Advance April 22, 2025, doi:10.1101/gr.279857.124
..., yielding a parameter-free formula for spatially dependent L-R signaling, significantly reducing the model complexity (Supplemental Fig. S28). stMLnet can serve as a hypothesis-generating tool in CCC studies, which can guide further experimental validations. For example, the L-R signaling-mediated feedback...
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Method: A Bayesian framework for inferring dynamic intercellular interactions from time-series single-cell data
- Cameron Park,
- Shouvik Mani,
- Nicolas Beltran-Velez,
- Katie Maurer,
- Teddy Huang,
- Shuqiang Li,
- Satyen Gohil,
- Kenneth J. Livak,
- David A. Knowles,
- Catherine J. Wu,
- and Elham Azizi
Genome Res. September 2024 34: 1384-1396; Published in Advance September 5, 2024, doi:10.1101/gr.279126.124
...and hypothesis generation for future investigations.DIISCO characterizes dynamic interactions between CAR T and lymphoma cellsTo demonstrate an application of DIISCO to biological data, we generated single-cell data from a controlled in vitro experimental setting. Specifically, we cocultured green fluorescent...
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Perspective: Unraveling the hidden complexity of cancer through long-read sequencing
- Qiuhui Li,
- Ayse G. Keskus,
- Justin Wagner,
- Michal B. Izydorczyk,
- Winston Timp,
- Fritz J. Sedlazeck,
- Alison P. Klein,
- Justin M. Zook,
- Mikhail Kolmogorov,
- and Michael C. Schatz
Genome Res. April 2025 35: 599-620; Published in Advance March 20, 2025, doi:10.1101/gr.280041.124
...important to this day due to their predictable performance and low costs.More recently, short-read sequencing has gained widespread adoption for cancer research as it enables the -wide identification of alterations, including single-nucleotide variants (SNVs), small insertions and deletions (indels), copy...
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Method: Pangenome-spanning epistasis and coselection analysis via de Bruijn graphs
- Juri Kuronen,
- Samuel T. Horsfield,
- Anna K. Pöntinen,
- Sudaraka Mallawaarachchi,
- Sergio Arredondo-Alonso,
- Harry Thorpe,
- Rebecca A. Gladstone,
- Rob J.L. Willems,
- Stephen D. Bentley,
- Nicholas J. Croucher,
- Johan Pensar,
- John A. Lees,
- Gerry Tonkin-Hill,
- and Jukka Corander
Genome Res. July 2024 34: 1081-1088; Published in Advance August 12, 2024, doi:10.1101/gr.278485.123
...(Skwark et al. 2017; Pensar et al. 2019; Top et al. 2020; Chewapreecha et al. 2022).The GWES approach can be considered as a phenotype-free biological hypothesis generator that works in a complementary manner compared with -wide association study (GWAS), which also aims to generate hypotheses of causal...
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Resource: Allele-specific transcription factor binding across human brain regions offers mechanistic insight into eQTLs
- Ashlyn G. Anderson,
- Belle A. Moyers,
- Jacob M. Loupe,
- Ivan Rodriguez-Nunez,
- Stephanie A. Felker,
- James M.J. Lawlor,
- William E. Bunney,
- Blynn G. Bunney,
- Preston M. Cartagena,
- Adolfo Sequeira,
- Stanley J. Watson,
- Huda Akil,
- Eric M. Mendenhall,
- Gregory M. Cooper,
- and Richard M. Myers
Genome Res. August 2024 34: 1224-1234; Published in Advance August 16, 2024, doi:10.1101/gr.278601.123
...with known eQTLs to facilitate fine-mapping and mechanistic hypothesis generation. For example, we highlight a case of a variant in an eQTL that displays ASB in our data set and specifically disrupts a motif for that TF (Fig. 5A–D). Although many variants exhibited allele-specific expression...
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Research: Variation in histone configurations correlates with gene expression across nine inbred strains of mice
- Anna L Tyler,
- Catrina Spruce,
- Romy Kursawe,
- Annat Haber,
- Robyn L Ball,
- Wendy A Pitman,
- Alexander D Fine,
- Narayanan Raghupathy,
- Michael Walker,
- Vivek M Philip,
- Christopher L Baker,
- J. Matthew Mahoney,
- Gary A. Churchill,
- Jennifer J Trowbridge,
- Michael L Stitzel,
- Kenneth Paigen,
- Petko M Petkov,
- and Gregory W Carter
Genome Res. May 22, 2023 gr.277467.122; Published in Advance May 22, 2023, doi:10.1101/gr.277467.122
...relative to293 the 9 inbred strains.294 Hypothesis generation for cis-regulatory regions295 By aligning associations with gene expression from the DO mice with inbred epigenetic features, we296 can generate hypotheses about heritable cis-regulatory regions in these mice. In particular, for any297 gene...
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Method: Identifying gene function and module connections by the integration of multispecies expression compendia
- Hao Li,
- Daria Rukina,
- Fabrice P.A. David,
- Terytty Yang Li,
- Chang-Myung Oh,
- Arwen W. Gao,
- Elena Katsyuba,
- Maroun Bou Sleiman,
- Andrea Komljenovic,
- Qingyao Huang,
- Robert W. Williams,
- Marc Robinson-Rechavi,
- Kristina Schoonjans,
- Stephan Morgenthaler,
- and Johan Auwerx
Genome Res. December 2019 29: 2034-2045; Published in Advance November 21, 2019, doi:10.1101/gr.251983.119
...genes) but with high association based on expression (M-MAD) (Fig. 5C). Moreover, many module pairs have predicted negative associations (Fig. 5C). Therefore, these results provide a resource for hypothesis generation and validation of the module connections.By applying M-MAD, we observed a strong...
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Research: Transposon insertional mutagenesis in Saccharomyces uvarum reveals trans-acting effects influencing species-dependent essential genes
- Monica R. Sanchez,
- Celia Payen,
- Frances Cheong,
- Blake T. Hovde,
- Sarah Bissonnette,
- Adam P. Arkin,
- Jeffrey M. Skerker,
- Rachel B. Brem,
- Amy A. Caudy,
- and Maitreya J. Dunham
Genome Res. March 2019 29: 396-406; Published in Advance January 11, 2019, doi:10.1101/gr.232330.117
...functions and/or different genetic interactions. Comprehensive gene dispensability comparisons with S. cerevisiae predicted diverged dispensability at 12% of conserved orthologs, and validation experiments confirmed 22 differentially essential genes. Despite their differences in essentiality, these genes...

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