Abstract

Gram-negative bacteria can deliver secreted proteins (also known as secreted effectors) directly into host cells through type III secretion system (T3SS), type IV secretion system (T4SS), and type VI secretion system (T6SS) and cause various diseases. These secreted effectors are heavily involved in the interactions between bacteria and host cells, so their identification is crucial for the discovery and development of novel anti-bacterial drugs. It is currently challenging to accurately distinguish type III secreted effectors (T3SEs) and type IV secreted effectors (T4SEs) because neither T3SEs nor T4SEs contain N-terminal signal peptides, and some of these effectors have similar evolutionary conserved profiles and sequence motifs. To address this challenge, we develop a deep learning (DL) approach called DeepT3_4 to correctly classify T3SEs and T4SEs. We generate amino-acid character dictionary and sequence-based features extracted from effector proteins and subsequently implement these features into a hybrid model that integrates recurrent neural networks (RNNs) and deep neural networks (DNNs). After training the model, the hybrid neural network classifies secreted effectors into two different classes with an accuracy, F-value, and recall of over 80.0%. Our approach stands for the first DL approach for the classification of T3SEs and T4SEs, providing a promising supplementary tool for further secretome studies.

Highlights

  • Protein secretion plays an important role in coordinating the interactions between bacteria and their surrounding environment

  • Our results show that a hybrid neural network performs better than other models on the test and independent test datasets, enabling accurate classification of T3SEs and T4SEs

  • (Wang et al, 2019b) and convolutional neural networks (CNNs)-T4SE (Hong et al, 2020) for T4SEs. Different from these studies, we developed a hybrid deep learning (DL) approach by integrating recurrent neural networks (RNNs) and deep neural networks (DNNs) architectures to classify T3SEs and T4SEs in this work

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Summary

Introduction

Protein secretion plays an important role in coordinating the interactions between bacteria and their surrounding environment. Within these secretion systems, T1SS, T2SS, and T5SS can transport enzymes and other proteins into the surrounding environment, while type III secretion system (T3SS), type IV secretion system (T4SS), and type VI secretion system (T6SS) can transfer various effector proteins into host cells directly. T1SS, T2SS, and T5SS can transport enzymes and other proteins into the surrounding environment, while type III secretion system (T3SS), type IV secretion system (T4SS), and type VI secretion system (T6SS) can transfer various effector proteins into host cells directly These secreted effectors released through the latter three secretion systems are generally referred to as type III secreted effectors (T3SEs), type IV secreted effectors (T4SEs), and type VI secreted effectors (T6SEs) (An et al, 2018), and they can exert the virulence of Gram-negative bacteria in a number of ways, severely disrupting the normal function of host cells (Kim, 2018). An in-depth study of secreted effectors is highly desirable for understanding the pathogenesis of bacteria and developing novel anti-microbial agents

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