RESEARCH Open Access

SCLpredT: Ab initio and homology-based prediction of subcellular localization by N-to-1 neural networks Alessandro Adelfio1,2, Viola Volpato1,2 and Gianluca Pollastri1,2* The prediction of protein subcellular localization is a important step towards the prediction of protein function, and considerable effort has gone over the last decade into the development of computational predictors of protein localization. In this article we design a new predictor of protein subcellular localization, based on a Machine Learning model (N-to-1 Neural Networks) which we have recently developed. This system, in three versions specialised, respectively, on Plants, Fungi and Animals, has a rich output which incorporates the class “organelle ” alongside cytoplasm, nucleus, mitochondria and extracellular, and, additionally, chloroplast in the case of Plants. We investigate the information gain of introducing additional inputs, including predicted secondary structure, and localization information from homologous sequences. To accommodate the latter we design a new algorithm which we present here for the first time. While we do not observe any improvement when including predicted secondary structure, we measure significant overall gains when adding homology information. The final predictor including homology information correctly predicts 74%, 79 % and 60 % of all proteins in the case of Fungi, Animals and Plants, respectively, and outperforms our previous, state-of-the-art predictor SCLpred, and the popular predictor BaCelLo. We also observe that the contribution of homology information becomes dominant over sequence information for sequence identity values exceeding 50 % for Animals and Fungi, and 60 % for Plants, confirming that subcellular localization is less conserved than structure. SCLpredT is publicly available a