NNTox: Gene Ontology-Based Protein Toxicity Prediction Using Neural Network

Sci Rep. 2019 Nov 29;9(1):17923. doi: 10.1038/s41598-019-54405-6.


With advancements in synthetic biology, the cost and the time needed for designing and synthesizing customized gene products have been steadily decreasing. Many research laboratories in academia as well as industry routinely create genetically engineered proteins as a part of their research activities. However, manipulation of protein sequences could result in unintentional production of toxic proteins. Therefore, being able to identify the toxicity of a protein before the synthesis would reduce the risk of potential hazards. Existing methods are too specific, which limits their application. Here, we extended general function prediction methods for predicting the toxicity of proteins. Protein function prediction methods have been actively studied in the bioinformatics community and have shown significant improvement over the last decade. We have previously developed successful function prediction methods, which were shown to be among top-performing methods in the community-wide functional annotation experiment, CAFA. Based on our function prediction method, we developed a neural network model, named NNTox, which uses predicted GO terms for a target protein to further predict the possibility of the protein being toxic. We have also developed a multi-label model, which can predict the specific toxicity type of the query sequence. Together, this work analyses the relationship between GO terms and protein toxicity and builds predictor models of protein toxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Gene Ontology
  • Humans
  • Neural Networks, Computer*
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / toxicity
  • Sequence Analysis, Protein / methods*
  • Software
  • Toxins, Biological / chemistry*
  • Toxins, Biological / genetics
  • Toxins, Biological / toxicity


  • Proteins
  • Toxins, Biological