Abstract

BackgroundThe prediction of protein subcellular localization is a key step of the big effort towards protein functional annotation. Many computational methods exist to identify high-level protein subcellular compartments such as nucleus, cytoplasm or organelles. However, many organelles, like mitochondria, have their own internal compartmentalization. Knowing the precise location of a protein inside mitochondria is crucial for its accurate functional characterization. We recently developed DeepMito, a new method based on a 1-Dimensional Convolutional Neural Network (1D-CNN) architecture outperforming other similar approaches available in literature.ResultsHere, we explore the adoption of DeepMito for the large-scale annotation of four sub-mitochondrial localizations on mitochondrial proteomes of five different species, including human, mouse, fly, yeast and Arabidopsis thaliana. A significant fraction of the proteins from these organisms lacked experimental information about sub-mitochondrial localization. We adopted DeepMito to fill the gap, providing complete characterization of protein localization at sub-mitochondrial level for each protein of the five proteomes. Moreover, we identified novel mitochondrial proteins fishing on the set of proteins lacking any subcellular localization annotation using available state-of-the-art subcellular localization predictors. We finally performed additional functional characterization of proteins predicted by DeepMito as localized into the four different sub-mitochondrial compartments using both available experimental and predicted GO terms. All data generated in this study were collected into a database called DeepMitoDB (available at http://busca.biocomp.unibo.it/deepmitodb), providing complete functional characterization of 4307 mitochondrial proteins from the five species.ConclusionsDeepMitoDB offers a comprehensive view of mitochondrial proteins, including experimental and predicted fine-grain sub-cellular localization and annotated and predicted functional annotations. The database complements other similar resources providing characterization of new proteins. Furthermore, it is also unique in including localization information at the sub-mitochondrial level. For this reason, we believe that DeepMitoDB can be a valuable resource for mitochondrial research.

Highlights

  • The prediction of protein subcellular localization is a key step of the big effort towards protein functional annotation

  • DeepMitoDB offers a comprehensive view of mitochondrial proteins, including experimental and predicted fine-grain sub-cellular localization and annotated and predicted functional annotations

  • We believe that DeepMitoDB can be a valuable resource for mitochondrial research

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Summary

Introduction

The prediction of protein subcellular localization is a key step of the big effort towards protein functional annotation. Available tools roughly belong to two main categories: (i) approaches that try to detect specific sorting signals such as signal or organelle-targeting peptides [5,6,7,8,9,10,11]; (ii) general methods predicting SL using features extracted from the entire protein sequence [12,13,14,15,16,17] In both cases, methods mainly predict the localization of proteins into main compartments, such as nucleus, cytoplasm, organelles, ER, plasma membrane and extracellular space. We develop DeepMito [26], a novel approach based on convolutional neural networks, able to discriminate all four mitochondrial compartments and outperforming other methods in literature [27]

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