4.7 Article

RFPR-IDP: reduce the false positive rates for intrinsically disordered protein and region prediction by incorporating both fully ordered proteins and disordered proteins

Journal

BRIEFINGS IN BIOINFORMATICS
Volume 22, Issue 2, Pages 2000-2011

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/bib/bbaa018

Keywords

intrinsically disordered proteins and regions; fully ordered proteins; convolution neural network; bidirectional long short-term memory

Funding

  1. National Natural Science Foundation of China [61822306, 61672184, 61732012 61573118]
  2. Beijing Natural Science Foundation [JQ19019]
  3. Fok Ying-Tung Education Foundation for Young Teachers in the Higher Education Institutions of China [161063]
  4. Scientific Research Foundation in Shenzhen [JCYJ20180306172207178, JCYJ20170307150528934, JCYJ20170811153836555]

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Intrinsically disordered proteins/regions (IDPs/IDRs) are important for biological functions, and accurate prediction is crucial for protein structure and function predictions. However, most existing methods tend to predict fully ordered proteins as disordered, ignoring the fact that most newly sequenced proteins are fully ordered. The proposed RFPR-IDP method, trained on both ordered and disordered proteins, outperforms existing predictors in predicting both ordered and disordered proteins.
As an important type of proteins, intrinsically disordered proteins/regions (IDPs/IDRs) are related to many crucial biological functions. Accurate prediction of IDPs/IDRs is beneficial to the prediction of protein structures and functions. Most of the existing methods ignore the fully ordered proteins without IDRs during training and test processes. As a result, the corresponding predictors prefer to predict the fully ordered proteins as disordered proteins. Unfortunately, these methods were only evaluated on datasets consisting of disordered proteins without or with only a few fully ordered proteins, and therefore, this problem escapes the attention of the researchers. However, most of the newly sequenced proteins are fully ordered proteins in nature. These predictors fail to accurately predict the ordered and disordered proteins in real-world applications. In this regard, we propose a new method called RFPR-IDP trained with both fully ordered proteins and disordered proteins, which is constructed based on the combination of convolution neural network (CNN) and bidirectional long short-term memory (BiLSTM). The experimental results show that although the existing predictors perform well for predicting the disordered proteins, they tend to predict the fully ordered proteins as disordered proteins. In contrast, the RFPR-IDP predictor can correctly predict the fully ordered proteins and outperform the other 10 state-of-the-art methods when evaluated on a test dataset with both fully ordered proteins and disordered proteins. The web server and datasets of RFPR-IDP are freely available at http://bliulab.net/RFPR-IDP/server.

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