Pmf-cpi: assessing drug selectivity with a pretrained multi-functional model for compound-protein interactions.

Compound-protein interactions (CPI) play significant roles in drug development. To avoid side effects, it is also crucial to evaluate drug selectivity when binding to different targets. However, most selectivity prediction models are constructed for specific targets with limited data. In this study, we present a pretrained multi-functional model for compound-protein interaction prediction (PMF-CPI) and fine-tune it to assess drug selectivity. This model uses recurrent neural networks to process the protein embedding based on the pretrained language model TAPE, extracts molecular information from a graph encoder, and produces the output from dense layers. PMF-CPI obtained the best performance compared to outstanding approaches on both the binding affinity regression and CPI classification tasks. Meanwhile, we apply the model to analyzing drug selectivity after fine-tuning it on three datasets related to specific targets, including human cytochrome P450s. The study shows that PMF-CPI can accurately predict different drug affinities or opposite interactions toward similar targets, recognizing selective drugs for precise therapeutics.Kindly confirm if corresponding authors affiliations are identified correctly and amend if any.Yes, it is correct.

DeepFusionDTA: Drug-Target Binding Affinity Prediction With Information Fusion and Hybrid Deep-Learning Ensemble Model.

Identification of drug-target interaction (DTI) is the most important issue in the broad field of drug discovery. Using purely biological experiments to verify drug-target binding profiles takes lots of time and effort, so computational technologies for this task obviously have great benefits in reducing the drug search space. Most of computational methods to predict DTI are proposed to solve a binary classification problem, which ignore the influence of binding strength. Therefore, drug-target binding affinity prediction is still a challenging issue. Currently, lots of studies only extract sequence information that lacks feature-rich representation, but we consider more spatial features in order to merge various data in drug and target spaces. In this study, we propose a two-stage deep neural network ensemble model for detecting drug-target binding affinity, called DeepFusionDTA, via various information analysis modules. First stage is to utilize sequence and structure information to generate fusion feature map of candidate protein and drug pair through various analysis modules based deep learning. Second stage is to apply bagging-based ensemble learning strategy for regression prediction, and we obtain outstanding results by combining the advantages of various algorithms in efficient feature abstraction and regression calculation. Importantly, we evaluate our novel method, DeepFusionDTA, which delivers 1.5 percent CI increase on KIBA dataset and 1.0 percent increase on Davis dataset, by comparing with existing prediction tools, DeepDTA. Furthermore, the ideas we have offered can be applied to in-silico screening of the interaction space, to provide novel DTIs which can be experimentally pursued. The codes and data are available from https://github.com/guofei-tju/DeepFusionDTA.

DeepATT: a hybrid category attention neural network for identifying functional effects of DNA sequences.

Quantifying DNA properties is a challenging task in the broad field of human genomics. Since the vast majority of non-coding DNA is still poorly understood in terms of function, this task is particularly important to have enormous benefit for biology research. Various DNA sequences should have a great variety of representations, and specific functions may focus on corresponding features in the front part of learning model. Currently, however, for multi-class prediction of non-coding DNA regulatory functions, most powerful predictive models do not have appropriate feature extraction and selection approaches for specific functional effects, so that it is difficult to gain a better insight into their internal correlations. Hence, we design a category attention layer and category dense layer in order to select efficient features and distinguish different DNA functions. In this study, we propose a hybrid deep neural network method, called DeepATT, for identifying $919$ regulatory functions on nearly $5$ million DNA sequences. Our model has four built-in neural network constructions: convolution layer captures regulatory motifs, recurrent layer captures a regulatory grammar, category attention layer selects corresponding valid features for different functions and category dense layer classifies predictive labels with selected features of regulatory functions. Importantly, we compare our novel method, DeepATT, with existing outstanding prediction tools, DeepSEA and DanQ. DeepATT performs significantly better than other existing tools for identifying DNA functions, at least increasing $1.6\%$ area under precision recall. Furthermore, we can mine the important correlation among different DNA functions according to the category attention module. Moreover, our novel model can greatly reduce the number of parameters by the mechanism of attention and locally connected, on the basis of ensuring accuracy.

DeepAVP: A Dual-Channel Deep Neural Network for Identifying Variable-Length Antiviral Peptides.

Antiviral peptides (AVPs) have been experimentally verified to block virus into host cells, which have antiviral activity with decapeptide amide. Therefore, utilization of experimentally validated antiviral peptides is a potential alternative strategy for targeting medically important viruses. In this article, we propose a dual-channel deep neural network ensemble method for analyzing variable-length antiviral peptides. The LSTM channel can capture long-term dependencies for effectively studying original variable-length sequence data. The CONV channel can build dynamic neural network for analyzing the local evolution information. Also, our model can fine-tune the substitution matrix for specifically functional peptides. Applying it to a novel experimentally verified dataset, our AVPs predictor, DeepAVP, demonstrates state-of-the-art performance of [Formula: see text] accuracy and 0.85 MCC, which is far better than existing prediction methods for identifying antiviral peptides. Therefore, DeepAVP, web server for predicting the effective AVPs, would make significantly contributions to peptide-based antiviral research.