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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
...is driven in part by recognition of DNA sequence, genetic variation can influence TF–DNA associations and gene regulation. To identify variants that impact TF binding in human brain tissues, we assessed allele-specific binding (ASB) at heterozygous variants for 94 TFs in nine brain regions from two donors...
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Method: Estimation of allele-specific fitness effects across human protein-coding sequences and implications for disease
- Yi-Fei Huang and
- Adam Siepel
Genome Res. August 2019 29: 1310-1321; Published in Advance June 27, 2019, doi:10.1101/gr.245522.118
...than to synonymous mutations. Because synonymous mutations tend to occur at third codon positions, the spatial distribution of allele-specific selection coefficients exhibits a general three-nucleotide periodic pattern in coding regions. Inspection of individual genes reveals that LASSIE frequently...
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Research: High-throughput allele-specific expression across 250 environmental conditions
- Gregory A. Moyerbrailean,
- Allison L. Richards,
- Daniel Kurtz,
- Cynthia A. Kalita,
- Gordon O. Davis,
- Chris T. Harvey,
- Adnan Alazizi,
- Donovan Watza,
- Yoram Sorokin,
- Nancy Hauff,
- Xiang Zhou,
- Xiaoquan Wen,
- Roger Pique-Regi,
- and Francesca Luca
Genome Res. December 2016 26: 1627-1638; Published in Advance October 19, 2016, doi:10.1101/gr.209759.116
...conditions Analysis of ASE We used QuASAR quantitative allele specific analysis of reads to identify genes with evidence of ASE QuASAR Harvey et al 2015 identifies heterozygous genotypes and uses a beta binomial distribution to infer ASE in RNA seq data In the 89 treatment conditions we identified...
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Research: Diverse environmental perturbations reveal the evolution and context-dependency of genetic effects on gene expression levels
- Amanda J. Lea,
- Julie Peng,
- and Julien F. Ayroles
Genome Res. October 2022 32: 1826-1839; Published in Advance October 13, 2022, doi:10.1101/gr.276430.121
...forces that maintain context-dependent eQTLs, especially in high-powered studies exploring many types of cellular environments, remain limited.Here, we report a large-scale study in which we profiled -wide gene expression levels across 12 different cellular environments using 544 immortalized B cell...
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Research: Heritable variation of mRNA decay rates in yeast
- Jennifer M. Andrie,
- Jon Wakefield,
- and Joshua M. Akey
Genome Res. December 2014 24: 2000-2010; Published in Advance September 25, 2014, doi:10.1101/gr.175802.114
...statistical framework and measured allele-specific differences in mRNA decay rates in a diploid yeast hybrid created by mating two genetically diverse parental strains. We estimate that 31% of genes exhibit allelic differences in mRNA decay rates, of which 350 can be identified at a false discovery rate of 10...
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Perspective: Genomic approaches for understanding the genetics of complex disease
- William L. Lowe, Jr. and
- Timothy E. Reddy
Genome Res. October 2015 25: 1432-1441; doi:10.1101/gr.190603.115
...-associated variants are highly enriched in candidate regulatory elements. Allele-specific analyses of gene regulation can further prioritize variants that likely have a functional effect on disease mechanisms; and emerging high-throughput assays to quantify the activity of candidate regulatory elements...
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Research: Genome-wide evaluation of the effect of short tandem repeat variation on local DNA methylation
- Alejandro Martin-Trujillo,
- Paras Garg,
- Nihir Patel,
- Bharati Jadhav,
- and Andrew J. Sharp
Genome Res. February 2023 33: 184-196; Published in Advance December 28, 2022, doi:10.1101/gr.277057.122
...Vicker et al. 2013), or chromatin accessibility (Degner et al. 2012), thus providing insights into the underlying molecular mechanism of a given trait or disease. However, because of either statistical power or technical limitations, QTL studies have been mainly focused on common single-nucleotide variants...
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Research: Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers
- Aneta Mikulasova,
- Daniel Kent,
- Marco Trevisan-Herraz,
- Nefeli Karataraki,
- Kent T.M. Fung,
- Cody Ashby,
- Agata Cieslak,
- Shmuel Yaccoby,
- Frits van Rhee,
- Maurizio Zangari,
- Sharmilan Thanendrarajan,
- Carolina Schinke,
- Gareth J. Morgan,
- Vahid Asnafi,
- Salvatore Spicuglia,
- Chris A. Brackley,
- Anne E. Corcoran,
- Sophie Hambleton,
- Brian A. Walker,
- Daniel Rico,
- and Lisa J. Russell
Genome Res. July 2022 32: 1343-1354; Published in Advance December 21, 2021, doi:10.1101/gr.276042.121
...; patient-derived xenograft material) for CCND1 (A) and MAF (B) loci. Numbers in colored squares (red denotes high expression; blue, low expression) show gene expression detected by RNA-seq and displayed as Log2-normalized counts (Log2 NC). (GC) Germinal center. (*) Sample contains chromosomal translocation...
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Method: High-resolution simulations of chromatin folding at genomic rearrangements in malignant B cells provide mechanistic insights into proto-oncogene deregulation
- Daniel Rico,
- Daniel Kent,
- Nefeli Karataraki,
- Aneta Mikulasova,
- Rolando Berlinguer-Palmini,
- Brian A. Walker,
- Biola M. Javierre,
- Lisa J. Russell,
- and Chris A. Brackley
Genome Res. July 2022 32: 1355-1366; Published in Advance July 21, 2022, doi:10.1101/gr.276028.121
...); this is because there is enrichment of H3K27me3 at the promoter. There are also ‘active’ H3K4me1/3 modifications, which could indicate variation between alleles or across the population, with the gene sometimes expressed and sometimes repressed. Consistent with this, publicly available RNA-seq data (The ENCODE...
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Research: Diverse tumorigenic consequences of human papillomavirus integration in primary oropharyngeal cancers
- David E. Symer,
- Keiko Akagi,
- Heather M. Geiger,
- Yang Song,
- Gaiyun Li,
- Anne-Katrin Emde,
- Weihong Xiao,
- Bo Jiang,
- André Corvelo,
- Nora C. Toussaint,
- Jingfeng Li,
- Amit Agrawal,
- Enver Ozer,
- Adel K. El-Naggar,
- Zoe Du,
- Jitesh B. Shewale,
- Birgit Stache-Crain,
- Mark Zucker,
- Nicolas Robine,
- Kevin R. Coombes,
- and Maura L. Gillison
Genome Res. January 2022 32: 55-70; Published in Advance December 13, 2021, doi:10.1101/gr.275911.121
...-positive cancers that is statistically powered to detect significant, recurrent hotspots of HPV integration, using precise and unbiased genomics methods including WGS and RNA-seq. These findings demonstrate that our HPV integrant-mediated looping model, initially formulated based primarily on cell lines, also...
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