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Development of bioinformatics methods is a long, complex and resource-hungry process. Hundreds of these tools were released. While some methods are highly cited and used, many suffer relatively low citation rates. We empirically analyze a large collection of recently released methods in three diverse protein function and disorder prediction areas to identify key factors that contribute to increased citations.

We show that provision of a working web server significantly boosts citation rates. On average, methods with working web servers generate three times as many citations compared to tools that are available as only source code, have no code and no server, or are no longer available. This observation holds consistently across different research areas and publication years. We also find that differences in predictive performance are unlikely to impact citation rates. Overall, our empirical results suggest that a relatively low-cost investment into the provision and long-term support of web servers would substantially increase the impact of bioinformatics tools.

Anti-cancer peptides (ACPs) have recently emerged as promising therapeutic agents for cancer treatment. Due to the avalanche of protein sequence data in the post-genomic era, there is an urgent need to develop automated computational methods to enable fast and accurate identification of novel ACPs within the vast number of candidate proteins and peptides.

To address this, we propose a novel predictor named Anti-Cancer peptide Predictor with Feature representation Learning (ACPred-FL) for accurate prediction of ACPs based on sequence information. More specifically, we develop an effective feature representation learning model, with which we can extract and learn a set of informative features from a pool of support vector machine-based models trained using sequence-based feature descriptors. By doing so, the class label information of data samples is fully utilized. To improve the feature representation, we further employ a two-step feature selection technique, resulting in a most informative five-dimensional feature vector for the final peptide representation. Experimental results show that such five features provide the most discriminative power for identifying ACPs than currently available feature descriptors, highlighting the effectiveness of the proposed feature representation learning approach. The developed ACPred-FL method significantly outperforms state-of-the-art methods.

The web-server of ACPred-FL is available at http://server.malab.cn/ACPred-FL.

Supplementary data are available at Bioinformatics online.

Kinase-regulated phosphorylation is a ubiquitous type of post-translational modification (PTM) in both eukaryotic and prokaryotic cells. Phosphorylation plays fundamental roles in many signalling pathways and biological processes, such as protein degradation and protein-protein interactions. Experimental studies have revealed that signalling defects caused by aberrant phosphorylation are highly associated with a variety of human diseases, especially cancers. In light of this, a number of computational methods aiming to accurately predict protein kinase family-specific or kinase-specific phosphorylation sites have been established, thereby facilitating phosphoproteomic data analysis.

In this work, we present Quokka, a novel bioinformatics tool that allows users to rapidly and accurately identify human kinase family-regulated phosphorylation sites. Quokka was developed by using a variety of sequence scoring functions combined with an optimized logistic regression algorithm. We evaluated Quokka based on well-prepared up-to-date benchmark and independent test datasets, curated from the Phospho.ELM and UniProt databases, respectively. The independent test demonstrates that Quokka improves the prediction performance compared with state-of-the-art computational tools for phosphorylation prediction. In summary, our tool provides users with high-quality predicted human phosphorylation sites for hypothesis generation and biological validation.

The Quokka webserver and datasets are freely available at http://quokka.erc.monash.edu/.

Supplementary data are available at Bioinformatics online.

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/.

Supplementary data are available at Bioinformatics online.