RT Journal Article
SR Electronic
T1 Thousands of novel translated open reading frames in humans inferred by ribosome footprint profiling
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 031617
DO 10.1101/031617
A1 Anil Raj
A1 Sidney H. Wang
A1 Heejung Shim
A1 Arbel Harpak
A1 Yang I. Li
A1 Brett Englemann
A1 Matthew Stephens
A1 Yoav Gilad
A1 Jonathan K. Pritchard
YR 2015
UL http://biorxiv.org/content/early/2015/11/25/031617.abstract
AB 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.