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bioRxiv · 10.1101/2021.06.02.446833

Systematic comparison of experimental assays and analytical pipelines for identification of active enhancers genome-wide

Yao, L.·Liang, J.·Ozer, A.·Leung, A. K.-Y.·ENCODE Consortium,·Lis, J. T.·Yu, H.
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Abstract

Mounting evidence supports the idea that transcriptional patterns serve as more specific identifiers of active enhancers than histone marks1,2; however, the optimal strategy to identify active enhancers both experimentally and computationally has not been determined. In this study, we compared 13 genome-wide RNA sequencing assays in K562 cells and showed that the nuclear run-on followed by cap-selection assay (namely, GRO/PRO-cap) has significant advantages in eRNA detection and active enhancer identification. We also introduced a new analytical tool, Peak Identifier for Nascent-Transcript Sequencing (PINTS), to identify active promoters and enhancers genome-wide and pinpoint the precise location of the 5 transcription start sites (TSSs) within these regulatory elements. Finally, we compiled a comprehensive enhancer candidate compendium based on the detected eRNA TSSs available in 120 cell and tissue types. To facilitate the exploration and prioritization of these enhancer candidates, we also built a user-friendly web server (https://pints.yulab.org) for the compendium with various additional genomic and epigenomic annotations. With the knowledge of the best available assays and pipelines, this large-scale annotation of candidate enhancers will pave the road for selection and characterization of their functions in a time-, labor-, and cost-effective manner in the future.

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Yao, L., Liang, J., Ozer, A., Leung, A. K.-Y., ENCODE Consortium,, Lis, J. T., Yu, H.. 2021-06-03. Systematic comparison of experimental assays and analytical pipelines for identification of active enhancers genome-wide. https://doi.org/10.1101/2021.06.02.446833

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