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Thousands of novel translated open reading frames in humans inferred by ribosome footprint profiling

Anil Raj, Sidney H. Wang, Heejung Shim, Arbel Harpak, Yang I. Li, Brett Englemann, Matthew Stephens, Yoav Gilad, Jonathan K. Pritchard
doi: https://doi.org/10.1101/031617
Anil Raj
1Department of Genetics, Stanford University, Stanford, CA
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  • For correspondence: rajanil@stanford.edu siddisis@uchicago.edu gilad@uchicago.edu pritch@stanford.edu
Sidney H. Wang
2Department of Human Genetics, University of Chicago, Chicago, IL
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  • For correspondence: rajanil@stanford.edu siddisis@uchicago.edu gilad@uchicago.edu pritch@stanford.edu
Heejung Shim
2Department of Human Genetics, University of Chicago, Chicago, IL
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Arbel Harpak
4Department of Biology, Stanford University, Stanford, CA
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Yang I. Li
1Department of Genetics, Stanford University, Stanford, CA
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Brett Englemann
2Department of Human Genetics, University of Chicago, Chicago, IL
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Matthew Stephens
2Department of Human Genetics, University of Chicago, Chicago, IL
3Department of Statistics, University of Chicago, Chicago, IL
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Yoav Gilad
2Department of Human Genetics, University of Chicago, Chicago, IL
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  • For correspondence: rajanil@stanford.edu siddisis@uchicago.edu gilad@uchicago.edu pritch@stanford.edu
Jonathan K. Pritchard
1Department of Genetics, Stanford University, Stanford, CA
4Department of Biology, Stanford University, Stanford, CA
5Howard Hughes Medical Institute
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  • For correspondence: rajanil@stanford.edu siddisis@uchicago.edu gilad@uchicago.edu pritch@stanford.edu
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Abstract

Accurate annotation of protein coding regions is essential for understanding how genetic information is translated into biological functions. Here we describe riboHMM, a new method that uses ribosome footprint data along with gene expression and sequence information to accurately infer translated sequences. We applied our method to human lymphoblastoid cell lines and identified 7,273 previously unannotated coding sequences, including 2,442 translated upstream open reading frames. We observed an enrichment of harringtonine-treated ribosome footprints at the inferred initiation sites, validating many of the novel coding sequences. The novel sequences exhibit significant signatures of selective constraint in the reading frames of the inferred proteins, suggesting that many of these are functional. Nearly 40% of bicistronic transcripts showed significant negative correlation in the levels of translation of their two coding sequences, suggesting a key regulatory role for these novel translated sequences. Our work significantly expands the set of known coding regions in humans.

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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-ND 4.0 International license.
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Posted November 25, 2015.
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Thousands of novel translated open reading frames in humans inferred by ribosome footprint profiling
Anil Raj, Sidney H. Wang, Heejung Shim, Arbel Harpak, Yang I. Li, Brett Englemann, Matthew Stephens, Yoav Gilad, Jonathan K. Pritchard
bioRxiv 031617; doi: https://doi.org/10.1101/031617
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Thousands of novel translated open reading frames in humans inferred by ribosome footprint profiling
Anil Raj, Sidney H. Wang, Heejung Shim, Arbel Harpak, Yang I. Li, Brett Englemann, Matthew Stephens, Yoav Gilad, Jonathan K. Pritchard
bioRxiv 031617; doi: https://doi.org/10.1101/031617

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