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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
..., a particular gene of interest (GOI) remains a persistent experimental and conceptual challenge. This gene-centric question is complicated by the multilayered regulatory environment in which each gene resides, comprising 3D chromatin structure, enhancer–promoter looping, DNA accessibility, histone modifications...
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Method: Aggregation of recount3 RNA-seq data improves inference of consensus and tissue-specific gene coexpression networks
- Prashanthi Ravichandran,
- Princy Parsana,
- Rebecca Keener,
- Kasper D. Hansen,
- and Alexis Battle
Genome Res. September 2025 35: 2087-2103; Published in Advance July 17, 2025, doi:10.1101/gr.280808.125
...corresponding to CNS (Fig. 3C), skin, liver, and lung were enriched for genes associated with tissue-matched GO terms (Supplemental Fig. S20). In addition, we examined the enrichment of central genes from tissue-specific gold standards obtained from HumanBase (https://hb.flatironinstitute.org/). We observed...
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Research: A quantitative framework for characterizing the evolutionary history of mammalian gene expression
- Jenny Chen,
- Ross Swofford,
- Jeremy Johnson,
- Beryl B. Cummings,
- Noga Rogel,
- Kerstin Lindblad-Toh,
- Wilfried Haerty,
- Federica di Palma,
- and Aviv Regev
Genome Res. January 2019 29: 53-63; Published in Advance December 14, 2018, doi:10.1101/gr.237636.118
...Hughes Medical Institute, Chevy Chase, Maryland 20815, USA Corresponding author: aregev@broadinstitute.orgAbstractThe evolutionary history of a gene helps predict its function and relationship to phenotypic traits. Although sequence conservation is commonly used to decipher gene function and assess...
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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
...K4me3 and gene expression is more408 complex that simple activation.409 The merging of DO expression quantitative trait loci with inbred chromatin state maps offers a410 potential method to identify cis-regulatory regions. The Pkd2 example illustrates how this could be411 done. Given...
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Research: Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits
- Peter Orchard,
- Nandini Manickam,
- Christa Ventresca,
- Swarooparani Vadlamudi,
- Arushi Varshney,
- Vivek Rai,
- Jeremy Kaplan,
- Claudia Lalancette,
- Karen L. Mohlke,
- Katherine Gallagher,
- Charles F. Burant,
- and Stephen C.J. Parker
Genome Res. December 2021 31: 2258-2275; Published in Advance November 23, 2021, doi:10.1101/gr.268482.120
...multi-omics profiling (gene expression and chromatin accessibility) on human and rat muscle samples. We capture type I and type II muscle fiber signatures, which are generally missed by existing single-cell RNA-seq methods. We perform cross-modality and cross-species integrative analyses on 33...
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Research: Relative contributions of sex hormones, sex chromosomes, and gonads to sex differences in tissue gene regulation
- Montgomery Blencowe,
- Xuqi Chen,
- Yutian Zhao,
- Yuichiro Itoh,
- Caden N. McQuillen,
- Yanjie Han,
- Benjamin L. Shou,
- Rebecca McClusky,
- Karen Reue,
- Arthur P. Arnold,
- and Xia Yang
Genome Res. May 2022 32: 807-824; Published in Advance April 8, 2022, doi:10.1101/gr.275965.121
...the DEGs highlighted in the 1WA overlap with genes previously identified to have SNPs associated with human diseases/pathogenic traits by GWAS. In brief, we mapped each of the GWAS SNPs to genes using liver and adipose eQTLs to represent disease-associated genes informed by GWAS. The mouse orthologs...
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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
...are organized by the module similarities. Dot sizes are proportional to MMASs of the respective modules. (C,D) Transcripts of genes encoding for ribosomal proteins in the liver negatively correlate with metabolic traits, such as body weight, fat mass, plasma glucose and cholesterol levels, in the BXD (C...
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Research: Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits
- Olivia Corradin,
- Alina Saiakhova,
- Batool Akhtar-Zaidi,
- Lois Myeroff,
- Joseph Willis,
- Richard Cowper-Sal·lari,
- Mathieu Lupien,
- Sanford Markowitz,
- and Peter C. Scacheri
Genome Res. January 2014 24: 1-13; Published in Advance November 6, 2013, doi:10.1101/gr.164079.113
...disorder, and Alzheimer’s disease correlated with enhancer–gene predictions made in neural precursor cells (NPC) (Fig. 6C). We quantified the number of liver-related traits found in the HepG2 trait cluster versus those in different cell types. Approximately 63% of the HepG2 cluster was comprised of liver...
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Method: High-throughput characterization of genetic effects on DNA–protein binding and gene transcription
- Cynthia A. Kalita,
- Christopher D. Brown,
- Andrew Freiman,
- Jenna Isherwood,
- Xiaoquan Wen,
- Roger Pique-Regi,
- and Francesca Luca
Genome Res. November 2018 28: 1701-1708; Published in Advance September 25, 2018, doi:10.1101/gr.237354.118
...mechanism leading to specific phenotypes is likely through disruption of gene regulatory sequence. Quantitative trait loci (QTLs) for molecular and cellular phenotypes (Dermitzakis 2012), such as gene expression (eQTL) (Brem and Kruglyak 2005; Stranger 2007; Innocenti et al. 2011; Wen et al. 2015; GTEx...
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Research: Tandem repeat variation in human and great ape populations and its impact on gene expression divergence
- Tugce Bilgin Sonay,
- Tiago Carvalho,
- Mark D. Robinson,
- Maja P. Greminger,
- Michael Krützen,
- David Comas,
- Gareth Highnam,
- David Mittelman,
- Andrew Sharp,
- Tomàs Marques-Bonet,
- and Andreas Wagner
Genome Res. November 2015 25: 1591-1599; Published in Advance August 19, 2015, doi:10.1101/gr.190868.115
...are accessible regions of DNA associated with gene regulatoryelements (Gross andGarrard 1988).We found that60%ofTRsoverlap aDNasehypersensitive site. The significant enrichment of repeats in DNase hypersensitive sites (P-value = 10−350) suggests that a substantial part of repeat sequences could potentially...

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