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Identification of essential regulatory elements in the human genome

Alex Wells, David Heckerman, Ali Torkamani, Li Yin, Bing Ren, View ORCID ProfileAmalio Telenti, Julia di Iulio
doi: https://doi.org/10.1101/444562
Alex Wells
1Stanford University, Stanford, CA 94305
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David Heckerman
2Department of Computer Sciences, University of California Los Angeles, Los Angeles, CA 90024, USA
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Ali Torkamani
3Scripps Research Translational Institute, La Jolla, CA 92037
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Li Yin
3Scripps Research Translational Institute, La Jolla, CA 92037
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Bing Ren
4Ludwig Institute for Cancer Research, La Jolla, CA 92093
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Amalio Telenti
3Scripps Research Translational Institute, La Jolla, CA 92037
5Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037
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  • ORCID record for Amalio Telenti
  • For correspondence: jdiiulio@scripps.edu atelenti@scripps.edu
Julia di Iulio
3Scripps Research Translational Institute, La Jolla, CA 92037
5Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037
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  • For correspondence: jdiiulio@scripps.edu atelenti@scripps.edu
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Abstract

The identification of essential regulatory elements is central to the understanding of the consequences of genetic variation. Here we use novel genomic data and machine learning techniques to map essential regulatory elements and to guide functional validation. We train an XGBoost model using 38 functional and structural features, including genome essentiality metrics, 3D genome organization and enhancer reporter STARR-seq data to differentiate between pathogenic and control non-coding genetic variants. We validate the accuracy of prediction by using data from tiling-deletion-based and CRISPR interference screens of activity of cis-regulatory elements. In neurodevelopmental disorders, the model (ncER, non-coding Essential Regulation) maps essential genomic segments within deletions and rearranged topologically associated domains linked to human disease. We show that the approach successfully identifies essential regulatory elements in the human genome.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted October 16, 2018.
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Identification of essential regulatory elements in the human genome
Alex Wells, David Heckerman, Ali Torkamani, Li Yin, Bing Ren, Amalio Telenti, Julia di Iulio
bioRxiv 444562; doi: https://doi.org/10.1101/444562
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Identification of essential regulatory elements in the human genome
Alex Wells, David Heckerman, Ali Torkamani, Li Yin, Bing Ren, Amalio Telenti, Julia di Iulio
bioRxiv 444562; doi: https://doi.org/10.1101/444562

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