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Moonlighting protein prediction using physico-chemical and evolutional properties via machine learning methods.

Farshid Shirafkan1, Sajjad Gharaghani2, Karim Rahimian3

  • 1Laboratory of Bioinformatics and Drug Design, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

BMC Bioinformatics
|May 25, 2021
PubMed
Summary

This study introduces a computational model to identify moonlighting proteins (MPs) and potential outliers. The model effectively predicts MPs, revealing that some non-MPs may also exhibit moonlighting functions.

Keywords:
Moonlighting proteinMultitasking proteinsOutlierPSSMPhysico-chemical propertiesRandom forestSVMbioinformatics

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Area of Science:

  • * Biochemistry and Molecular Biology
  • * Computational Biology and Bioinformatics

Background:

  • * Moonlighting proteins (MPs) possess multiple distinct functions within a single polypeptide chain.
  • * Studying MPs is crucial for understanding cellular processes, protein evolution, and disease mechanisms.
  • * Experimental identification of MPs is challenging, necessitating computational prediction methods.

Purpose of the Study:

  • * To develop a computational model for accurately detecting moonlighting proteins (MPs) and non-MPs.
  • * To identify potential outlier proteins within protein datasets.
  • * To assess the performance of various classification methods and feature vectors for MP prediction.

Main Methods:

  • * Utilized 37 distinct feature vectors extracted from protein sequences.
  • * Employed 8 different classification methods, including Support Vector Machines (SVM).
  • * Implemented a rigorous tenfold cross-validation process repeated 100 times to identify outlier proteins based on misclassification frequency.

Main Results:

  • * The SVM method demonstrated the highest performance in predicting moonlighting proteins across all assessed feature vectors.
  • * Identified 57 potential outlier proteins from a dataset of 351 samples (215 MPs, 136 non-MPs).
  • * Discovered that some non-MPs, like P69797, were misclassified across multiple methods, suggesting potential moonlighting activity.

Conclusions:

  • * The developed computational approach effectively identifies novel moonlighting proteins.
  • * The study highlights the difficulty of experimental MP identification and the utility of computational tools.
  • * Findings suggest that several proteins currently classified as non-MPs may exhibit moonlighting functions.