AUTHOR=Zhang Ning, Rao R. S. P., Salvato Fernanda, Havelund Jesper F., Møller Ian M., Thelen Jay J., Xu Dong TITLE=MU-LOC: A Machine-Learning Method for Predicting Mitochondrially Localized Proteins in Plants JOURNAL=Frontiers in Plant Science VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/articles/10.3389/fpls.2018.00634 DOI=10.3389/fpls.2018.00634 ISSN=1664-462X ABSTRACT=Targeting and translocation of proteins to the appropriate subcellular compartments are crucial for cell organization and function. Newly synthesized proteins are transported to mitochondria with the assistance of complex targeting sequences containing either an N-terminal pre-sequence or a multitude of internal signals. Compared with experimental approaches, computational predictions provide an efficient way to infer subcellular localization of a protein. However, it is still challenging to predict plant mitochondrially localized proteins accurately due to various limitations. Consequently, the performance of current tools can be improved with new data and new machine-learning methods. We present MU-LOC, a novel computational approach for large-scale prediction of plant mitochondrial proteins. We collected a comprehensive dataset of plant subcellular localization, extracted features including amino acid composition, protein position weight matrix, and gene co-expression information, and trained predictors using deep neural network and support vector machine. Benchmarked on two independent datasets, MU-LOC achieved substantial improvements over six state-of-the-art tools for plant mitochondrial targeting prediction. In addition, MU-LOC has the advantage of predicting plant mitochondrial proteins either possessing or lacking N-terminal pre-sequences. We applied MU-LOC to predict candidate mitochondrial proteins for the whole proteome of Arabidopsis and potato. MU-LOC is publicly available at http://mu-loc.org.