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Method: Polyomino reconstructs spatial transcriptomic profiles with single-cell resolution via a region-allocation method
- Quanyou Cai,
- Lihui Lin,
- Xin Liu,
- and Jiekai Chen
Genome Res. November 2025 35: 2513-2526; Published in Advance October 22, 2025, doi:10.1101/gr.280532.125
...that tile the entire spatial profile containing capture area; each bin contains several spatial voxels. By leveraging the tissue architecture, spatial gene expression, or virtual generated structure, the bins are organized into diverse layers of regionalization, for example, virtually generated horizontal...
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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
..., hinging on the precise binding of transcription factors (TFs) and cofactors to gene regulatory elements such as promoters and enhancers. Although it is relatively routine to profile -wide DNA binding landscapes of proteins, identifying the specific proteins that bind to, and regulate the transcription of...
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Research: Analysis of a cell-free DNA–based cancer screening cohort links fragmentomic profiles, nuclease levels, and plasma DNA concentrations
- Yasine Malki,
- Guannan Kang,
- W.K. Jacky Lam,
- Qing Zhou,
- Suk Hang Cheng,
- Peter P.H. Cheung,
- Jinyue Bai,
- Ming Lok Chan,
- Chui Ting Lee,
- Wenlei Peng,
- Yiqiong Zhang,
- Wanxia Gai,
- Winsome W.S. Wong,
- Mary-Jane L. Ma,
- Wenshuo Li,
- Xinzhou Xu,
- Zhuoran Gao,
- Irene O.L. Tse,
- Huimin Shang,
- L.Y. Lois Choy,
- Peiyong Jiang,
- K.C. Allen Chan,
- and Y.M. Dennis Lo
Genome Res. January 2025 35: 31-42; Published in Advance November 27, 2024, doi:10.1101/gr.279667.124
.... The readings from fluorometric measurements (n = 25) were well correlated with results obtained from the droplet digital PCR assay, which targeted a single-copy gene valosin-containing protein (VCP) (Supplemental Fig. S3). This highlights the reliability of using fluorometric methods to reflect the total cf...
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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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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
...and AI Institute, Johns Hopkins University, Baltimore, Maryland 21218, USA Corresponding author: ajbattle@jhu.eduAbstractGene coexpression networks (GCNs) describe relationships among genes that maintain cellular identity and homeostasis. However, typical RNA-seq experiments often lack sufficient sample...
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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
...between genetic variants and environmental stressors is key to understanding the mechanisms underlying neurological diseases. In this study, we use human brain organoids to explore how varying oxygen levels expose context-dependent gene regulatory effects. By subjecting a genetically diverse panel of 21...
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Research: Genetic effects on chromatin accessibility uncover mechanisms of liver gene regulation and quantitative traits
- Kevin W. Currin,
- Hannah J. Perrin,
- Gautam K. Pandey,
- Abdalla A. Alkhawaja,
- Swarooparani Vadlamudi,
- Annie E. Musser,
- Amy S. Etheridge,
- K. Alaine Broadaway,
- Jonathan D. Rosen,
- Arushi Varshney,
- Amarjit S. Chaudhry,
- Paul J. Gallins,
- Fred A. Wright,
- Yi-hui Zhou,
- Stephen C.J. Parker,
- Laura M. Raffield,
- Erin G. Schuetz,
- Federico Innocenti,
- and Karen L. Mohlke
Genome Res. July 2025 35: 1485-1502; Published in Advance May 20, 2025, doi:10.1101/gr.279741.124
...elements that underlie genetic effects on gene expression and metabolic traits. However, caQTL discovery has been limited by small sample sizes. Here, we map caQTLs in liver tissue from 138 human donors and identify caQTLs for 35,361 regulatory elements, including population-specific caQTLs driven...
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Method: Accurate estimation of intraspecific microbial gene content variation in metagenomic data with MIDAS v3 and StrainPGC
- Byron J. Smith,
- Chunyu Zhao,
- Veronika Dubinkina,
- Xiaofan Jin,
- Liron Zahavi,
- Saar Shoer,
- Jacqueline Moltzau-Anderson,
- Eran Segal,
- and Katherine S. Pollard
Genome Res. May 2025 35: 1247-1260; Published in Advance April 10, 2025, doi:10.1101/gr.279543.124
...in situ is to quantify the gene families present in shotgun metas, an approach referred to as “pan profiling.” Pan profiling estimates the mean sequencing depth, sometimes called vertical coverage, of a gene family as the mean number of reads aligning to each base of a representative sequence (Milanese et...
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Resource: Common and specific gene regulatory programs in zebrafish caudal fin regeneration at single-cell resolution
- Yujie Chen,
- Yiran Hou,
- Qinglin Zeng,
- Irene Wang,
- Meiru Shang,
- Kwangdeok Shin,
- Christopher Hemauer,
- Xiaoyun Xing,
- Junsu Kang,
- Guoyan Zhao,
- and Ting Wang
Genome Res. January 2025 35: 202-218; Published in Advance January 14, 2025, doi:10.1101/gr.279372.124
...common and cell-type-specific regeneration-responsive gene (RRG) programs and cis-regulatory elements, as well as key TFs associated with stages and cell types during regeneration, enhancing our understanding of tissue regeneration.ResultsSingle-nucleus multiomic profiling of zebrafish caudal fin...
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Method: Spatially resolved whole transcriptome profiling in human and mouse tissue using Digital Spatial Profiling
- Stephanie M. Zimmerman,
- Robin Fropf,
- Bridget R. Kulasekara,
- Maddy Griswold,
- Oliver Appelbe,
- Arya Bahrami,
- Rich Boykin,
- Derek L. Buhr,
- Kit Fuhrman,
- Margaret L. Hoang,
- Quoc Huynh,
- Lesley Isgur,
- Andrew Klock,
- Alecksandr Kutchma,
- Alexa E. Lasley,
- Yan Liang,
- Jill McKay-Fleisch,
- Jeffrey S. Nelson,
- Karen Nguyen,
- Erin Piazza,
- Aric Rininger,
- Daniel R. Zollinger,
- Michael Rhodes,
- and Joseph M. Beechem
Genome Res. October 2022 32: 1892-1905; Published in Advance September 13, 2022, doi:10.1101/gr.276206.121
..., preserving the spatial and morphological context of gene expression. Here, we describe expanding the chemistry for the Digital Spatial Profiling platform to quantify whole transcriptomes in human and mouse tissues using a wide range of spatial profiling strategies and sample types. We designed multiplexed...
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