More Like this

1. DeepCleave: a deep learning predictor for caspase and matrix metalloprotease substrates and cleavage sites

   https://doi.org/10.1093/bioinformatics/btz721  

   Li, Fuyi ; Chen, Jinxiang ; Leier, André ; Marquez-Lago, Tatiana ; Liu, Quanzhong ; Wang, Yanze ; Revote, Jerico ; Smith, A. Ian ; Akutsu, Tatsuya ; Webb, Geoffrey I. ; et al ( September 2019 , Bioinformatics)

   Proteases are enzymes that cleave target substrate proteins by catalyzing the hydrolysis of peptide bonds between specific amino acids. While the functional proteolysis regulated by proteases plays a central role in the ‘life and death’ cellular processes, many of the corresponding substrates and their cleavage sites were not found yet. Availability of accurate predictors of the substrates and cleavage sites would facilitate understanding of proteases’ functions and physiological roles. Deep learning is a promising approach for the development of accurate predictors of substrate cleavage events.

   We propose DeepCleave, the first deep learning-based predictor of protease-specific substrates and cleavage sites. DeepCleave uses protein substrate sequence data as input and employs convolutional neural networks with transfer learning to train accurate predictive models. High predictive performance of our models stems from the use of high-quality cleavage site features extracted from the substrate sequences through the deep learning process, and the application of transfer learning, multiple kernels and attention layer in the design of the deep network. Empirical tests against several related state-of-the-art methods demonstrate that DeepCleave outperforms these methods in predicting caspase and matrix metalloprotease substrate-cleavage sites.

   The DeepCleave webserver and source code are freely available at http://deepcleave.erc.monash.edu/.

   Supplementarymore »data are available at Bioinformatics online.

   « less
2. 3D-equivariant graph neural networks for protein model quality assessment

   https://doi.org/10.1093/bioinformatics/btad030  

   Chen, Chen ; Chen, Xiao ; Morehead, Alex ; Wu, Tianqi ; Cheng, Jianlin ; Cowen, ed., Lenore ( January 2023 , Bioinformatics)

   Quality assessment (QA) of predicted protein tertiary structure models plays an important role in ranking and using them. With the recent development of deep learning end-to-end protein structure prediction techniques for generating highly confident tertiary structures for most proteins, it is important to explore corresponding QA strategies to evaluate and select the structural models predicted by them since these models have better quality and different properties than the models predicted by traditional tertiary structure prediction methods.

   We develop EnQA, a novel graph-based 3D-equivariant neural network method that is equivariant to rotation and translation of 3D objects to estimate the accuracy of protein structural models by leveraging the structural features acquired from the state-of-the-art tertiary structure prediction method—AlphaFold2. We train and test the method on both traditional model datasets (e.g. the datasets of the Critical Assessment of Techniques for Protein Structure Prediction) and a new dataset of high-quality structural models predicted only by AlphaFold2 for the proteins whose experimental structures were released recently. Our approach achieves state-of-the-art performance on protein structural models predicted by both traditional protein structure prediction methods and the latest end-to-end deep learning method—AlphaFold2. It performs even better than the model QA scores provided by AlphaFold2 itself.more »The results illustrate that the 3D-equivariant graph neural network is a promising approach to the evaluation of protein structural models. Integrating AlphaFold2 features with other complementary sequence and structural features is important for improving protein model QA.

   The source code is available at https://github.com/BioinfoMachineLearning/EnQA.

   Supplementary data are available at Bioinformatics online.

   « less
3. Accurately modeling biased random walks on weighted networks using node2vec+

   https://doi.org/10.1093/bioinformatics/btad047  

   Liu, Renming ; Hirn, Matthew ; Krishnan, Arjun ; Martelli, ed., Pier Luigi ( January 2023 , Bioinformatics)

   Accurately representing biological networks in a low-dimensional space, also known as network embedding, is a critical step in network-based machine learning and is carried out widely using node2vec, an unsupervised method based on biased random walks. However, while many networks, including functional gene interaction networks, are dense, weighted graphs, node2vec is fundamentally limited in its ability to use edge weights during the biased random walk generation process, thus under-using all the information in the network.

   Here, we present node2vec+, a natural extension of node2vec that accounts for edge weights when calculating walk biases and reduces to node2vec in the cases of unweighted graphs or unbiased walks. Using two synthetic datasets, we empirically show that node2vec+ is more robust to additive noise than node2vec in weighted graphs. Then, using genome-scale functional gene networks to solve a wide range of gene function and disease prediction tasks, we demonstrate the superior performance of node2vec+ over node2vec in the case of weighted graphs. Notably, due to the limited amount of training data in the gene classification tasks, graph neural networks such as GCN and GraphSAGE are outperformed by both node2vec and node2vec+.

   The data and code are available on GitHub atmore »https://github.com/krishnanlab/node2vecplus_benchmarks. All additional data underlying this article are available on Zenodo at https://doi.org/10.5281/zenodo.7007164.

   Supplementary data are available at Bioinformatics online.

   « less
4. Predicting serious rare adverse reactions of novel chemicals

   https://doi.org/10.1093/bioinformatics/bty193  

   Poleksic, Aleksandar ; Xie, Lei ; Wren, ed., Jonathan ( March 2018 , Bioinformatics)

   Adverse drug reactions (ADRs) are one of the main causes of death and a major financial burden on the world’s economy. Due to the limitations of the animal model, computational prediction of serious and rare ADRs is invaluable. However, current state-of-the-art computational methods do not yield significantly better predictions of rare ADRs than random guessing.

   We present a novel method, based on the theory of ‘compressed sensing’ (CS), which can accurately predict serious side-effects of candidate and market drugs. Not only is our method able to infer new chemical-ADR associations using existing noisy, biased and incomplete databases, but our data also demonstrate that the accuracy of CS in predicting a serious ADR for a candidate drug increases with increasing knowledge of other ADRs associated with the drug. In practice, this means that as the candidate drug moves up the different stages of clinical trials, the prediction accuracy of our method will increase accordingly.

   The program is available at https://github.com/poleksic/side-effects.

   Supplementary data are available at Bioinformatics online.
5. SubMito-XGBoost: predicting protein submitochondrial localization by fusing multiple feature information and eXtreme gradient boosting

   https://doi.org/10.1093/bioinformatics/btz734  

   Yu, Bin ; Qiu, Wenying ; Chen, Cheng ; Ma, Anjun ; Jiang, Jing ; Zhou, Hongyan ; Ma, Qin ; Hancock, ed., John ( October 2019 , Bioinformatics)

   Mitochondria are an essential organelle in most eukaryotes. They not only play an important role in energy metabolism but also take part in many critical cytopathological processes. Abnormal mitochondria can trigger a series of human diseases, such as Parkinson's disease, multifactor disorder and Type-II diabetes. Protein submitochondrial localization enables the understanding of protein function in studying disease pathogenesis and drug design.

   We proposed a new method, SubMito-XGBoost, for protein submitochondrial localization prediction. Three steps are included: (i) the g-gap dipeptide composition (g-gap DC), pseudo-amino acid composition (PseAAC), auto-correlation function (ACF) and Bi-gram position-specific scoring matrix (Bi-gram PSSM) are employed to extract protein sequence features, (ii) Synthetic Minority Oversampling Technique (SMOTE) is used to balance samples, and the ReliefF algorithm is applied for feature selection and (iii) the obtained feature vectors are fed into XGBoost to predict protein submitochondrial locations. SubMito-XGBoost has obtained satisfactory prediction results by the leave-one-out-cross-validation (LOOCV) compared with existing methods. The prediction accuracies of the SubMito-XGBoost method on the two training datasets M317 and M983 were 97.7% and 98.9%, which are 2.8–12.5% and 3.8–9.9% higher than other methods, respectively. The prediction accuracy of the independent test set M495 was 94.8%, which is significantly better than themore »existing studies. The proposed method also achieves satisfactory predictive performance on plant and non-plant protein submitochondrial datasets. SubMito-XGBoost also plays an important role in new drug design for the treatment of related diseases.

   The source codes and data are publicly available at https://github.com/QUST-AIBBDRC/SubMito-XGBoost/.

   Supplementary data are available at Bioinformatics online.

   « less