Flap-enabled next-generation capture (FENGC): precision targeted single-molecule profiling of epigenetic heterogeneity, chromatin dynamics, and genetic variation
Zhou, M.; Nabilsi, N. H.; Wang, A.; Gauthier, M.-P. L.; Murray, K. O.; Azari, H.; Owens, W. S.; Newman, J. R. B.; Pardo-Palacios, F. J.; Conesa, A.; Riva, A.; Clanton, T. L.; Reynolds, B. A.; Concannon, P.; Brant, J. O.; Bacher, R.; Kladde, M. P.
Show abstract
Targeted sequencing is an increasingly sought technology. Available methods, however, are often costly and yield high proportions of off-target reads. Here, we present FENGC, a scalable, multiplexed method in which target sequences are assembled into 5' flaps for precise excision by flap endonuclease. Recovery of length-matched sequences, amplification with universal primers, and exonucleolytic removal of non-targeted genomic regions mitigate amplification biases and consistently yield [≥] 80% on-target sequencing. Furthermore, optimized sequential reagent addition and purifications minimize sample loss and facilitate rapid processing of sub-microgram quantities of DNA for detection of genetic variants and DNA methylation. Treatment of cultured human glioblastoma cells and primary murine monocytes with GC methyltransferase followed by FENGC and high-coverage enzymatic methyl sequencing provides single-molecule, long-read detection of differential endogenous CG methylation, dynamic nucleosome repositioning, and transcription factor binding. FENGC provides a versatile and cost-effective platform for targeted sequence enrichment for analysis of genetic and/or epigenetic heterogeneity.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A human DNA methylation atlas reveals principles of cell type-specific methylation and identifies thousands of cell type-specific regulatory elements 97%
- An integrated transcriptomic and epigenomic atlas of mouse primary motor cortex cell types 97%
- Comprehensive analysis of clustered mutations in cancer reveals recurrent APOBEC3 mutagenesis of ecDNA 97%
Similar papers in this journal
- Targeted profiling of human extrachromosomal DNA by CRISPR-CATCH 97%
- ChIP-DIP: A multiplexed method for mapping hundreds of proteins to DNA uncovers diverse regulatory elements controlling gene expression 97%
- Tissue-specific enhancer-gene maps from multimodal single-cell data identify causal disease alleles 96%
Similar papers in this journal
- High throughput PRIME editing screens identify functional DNA variants in the human genome 97%
- Three-dimensional regulatory hubs support oncogenic programs in glioblastoma 96%
- Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 96%
Similar papers in this journal
- BamQuery: a proteogenomic tool for the genome-wide exploration of the immunopeptidome 97%
- Enhancer plasticity in endometrial tumorigenesis demarcates non-coding somatic mutations and 3D-genome alterations boosting the oncogenic driver ESR1 96%
- Comprehensive analyses of partially methylated domains and differentially methylated regions in esophageal cancer reveal both cell-type- and cancer-specific epigenetic regulation 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.