TY - JOUR T1 - Detecting sequence signals in targeting peptides using deep learning JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900429 VL - 2 IS - 5 SP - e201900429 AU - Jose Juan Almagro Armenteros AU - Marco Salvatore AU - Olof Emanuelsson AU - Ole Winther AU - Gunnar von Heijne AU - Arne Elofsson AU - Henrik Nielsen Y1 - 2019/10/01 UR - https://www.life-science-alliance.org/content/2/5/e201900429.abstract N2 - In bioinformatics, machine learning methods have been used to predict features embedded in the sequences. In contrast to what is generally assumed, machine learning approaches can also provide new insights into the underlying biology. Here, we demonstrate this by presenting TargetP 2.0, a novel state-of-the-art method to identify N-terminal sorting signals, which direct proteins to the secretory pathway, mitochondria, and chloroplasts or other plastids. By examining the strongest signals from the attention layer in the network, we find that the second residue in the protein, that is, the one following the initial methionine, has a strong influence on the classification. We observe that two-thirds of chloroplast and thylakoid transit peptides have an alanine in position 2, compared with 20% in other plant proteins. We also note that in fungi and single-celled eukaryotes, less than 30% of the targeting peptides have an amino acid that allows the removal of the N-terminal methionine compared with 60% for the proteins without targeting peptide. The importance of this feature for predictions has not been highlighted before. ER -