MLASSO-Hum: A LASSO-based interpretable human-protein subcellular localization predictor

Shibiao Wan, Man Wai Mak, Sun Yuan Kung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

19 Citations (Scopus)

Abstract

Knowing the subcellular compartments of human proteins is essential to shed light on the mechanisms of a broad range of human diseases. In computational methods for protein subcellular localization, knowledge-based methods (especially gene ontology (GO) based methods) are known to perform better than sequence-based methods. However, existing GO-based predictors often lack interpretability and suffer from overfitting due to the high dimensionality of feature vectors. To address these problems, this paper proposes an interpretable multi-label predictor, namely mLASSO-Hum, which can yield sparse and interpretable solutions for large-scale prediction of human protein subcellular localization. By using the one-vs-rest LASSO-based classifiers, 87 out of more than 8000 GO terms are found to play more significant roles in determining the subcellular localization. Based on these 87 essential GO terms, we can decide not only where a protein resides within a cell, but also why it is located there. To further exploit information from the remaining GO terms, a method based on the GO hierarchical information derived from the depth distance of GO terms is proposed. Experimental results show that mLASSO-Hum performs significantly better than state-of-the-art predictors. We also found that in addition to the GO terms from the cellular component category, GO terms from the other two categories also play important roles in the final classification decisions.
Original languageEnglish
Pages (from-to)223-234
Number of pages12
JournalJournal of Theoretical Biology
Volume382
DOIs
Publication statusPublished - 7 Oct 2015

Keywords

  • Depth-dependent information
  • Interpretable prediction
  • Multi-label classification
  • Protein subcellular localization
  • Sparse solutions

ASJC Scopus subject areas

  • Statistics and Probability
  • Modelling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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