A machine learning model that predicts ATG and near-cognate codon initiation sites (TIS) in nucleotide sequences

TIS Predictor is a machine learning software developed to predict translation initiation sites in a given nucleotide sequence [1]. It was trained on instances of ATG and near-cognate translation initiation. Furthermore, it outperforms the recently developed model, TITER [2], that had been created for the same function by more than 18% in accuracy.

Please cite this publication and/or this publication if predictions are used.

ATG translation-initiation codons are predicted with about 87.79% accuracy, and near-cognate codons (CTG, GTG and TTG) with 85.00% accuracy. Less common near-cognate codons are extrapolated (AAG, AGG, ACG, ATC, ATT, and ATA), based on patterns recognized from CTG, GTG, and TTG instances. Predictions for codons that the software was trained on show up in bold. Extrapolated codons show up without bold formatting (and should be akndowledged with less confidence).

Previously identified translation initiation sites upstream of repeat expansions for the C9ORF72, FMR1, DM1, and HDL2 genes – associated with neurologic disease – were compiled and used as a reference for software performance.

All translation initiation sites were correctly identified with one exception: ATC, seven bases upstream of the repeat [6]

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2.           Zhang S, Hu H, Jiang T, Zhang L, Zeng J. TITER : predicting translation initiation sites by deep learning. Bioinformatics. 2017:33:i234–i42.

3.           Boivin M, Pfister V, Gaucherot A, Ruffenach F, Luc N, Sellier C, et al. Reduced autophagy upon C9ORF72 loss synergizes with dipeptide repeat protein toxicity in G4C2 repeat expansion disorders. EMBO J. 2020;39(4):e100574.

4.           Rodriguez CM, Wright SE, Kearse MG, Haenfler JM, Flores BN, Liu Y, et al. A native function for RAN translation and CGG repeats in regulating fragile X protein synthesis. Nature Neuroscience. 2020;23:386–97.

5.           Kearse MG, Green KM, Krans A, Rodriguez CM, Linsalata AE, Goldstrohm AC, et al. CGG Repeat associated non-AUG translation utilizes a cap-dependent, scanning mechanism of initiation to produce toxic proteins. Mol Cell. 2016;62(2):314-22.

6.           Zu T, Gibbens B, Doty NS, Gomes-Pereira M, Huguet A, Stone MD, et al. Non-ATG-initiated translation directed by microsatellite expansions. Proc Natl Acad Sci U S A. 2010;108(1):260-5.