Protein subcellular localization prediction based on compartment-specific features and structure conservation

Emily Chia Yu Su, Hua Sheng Chiu, Allan Lo, Jenn Kang Hwang, Ting Yi Sung, Wen Lian Hsu

研究成果: 雜誌貢獻文章同行評審

54 引文 斯高帕斯(Scopus)

摘要

Background: Protein subcellular localization is crucial for genome annotation, protein function prediction, and drug discovery. Determination of subcellular localization using experimental approaches is time-consuming; thus, computational approaches become highly desirable. Extensive studies of localization prediction have led to the development of several methods including composition-based and homology-based methods. However, their performance might be significantly degraded if homologous sequences are not detected. Moreover, methods that integrate various features could suffer from the problem of low coverage in high-throughput proteomic analyses due to the lack of information to characterize unknown proteins. Results: We propose a hybrid prediction method for Gram-negative bacteria that combines a one-versus-one support vector machines (SVM) model and a structural homology approach. The SVM model comprises a number of binary classifiers, in which biological features derived from Gram-negative bacteria translocation pathways are incorporated. In the structural homology approach, we employ secondary structure alignment for structural similarity comparison and assign the known localization of the top-ranked protein as the predicted localization of a query protein. The hybrid method achieves overall accuracy of 93.7% and 93.2% using ten-fold cross-validation on the benchmark data sets. In the assessment of the evaluation data sets, our method also attains accurate prediction accuracy of 84.0%, especially when testing on sequences with a low level of homology to the training data. A three-way data split procedure is also incorporated to prevent overestimation of the predictive performance. In addition, we show that the prediction accuracy should be approximately 85% for non-redundant data sets of sequence identity less than 30%. Conclusion: Our results demonstrate that biological features derived from Gram-negative bacteria translocation pathways yield a significant improvement. The biological features are interpretable and can be applied in advanced analyses and experimental designs. Moreover, the overall accuracy of combining the structural homology approach is further improved, which suggests that structural conservation could be a useful indicator for inferring localization in addition to sequence homology. The proposed method can be used in large-scale analyses of proteomes.
原文英語
文章編號330
期刊BMC Bioinformatics
8
DOIs
出版狀態已發佈 - 九月 8 2007
對外發佈

ASJC Scopus subject areas

  • 醫藥 (全部)
  • 結構生物學
  • 應用數學

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