Attention mechanism models for precision medicine.

The development of deep learning models plays a crucial role in advancing precision medicine. These models enable personalized medical treatments and interventions based on the unique genetic, environmental and lifestyle factors of individual patients, and the promotion of precision medicine is achieved mainly through genomic data analysis, variant annotation and interpretation, pharmacogenomics research, biomarker discovery, disease typing, clinical decision support and disease mechanism interpretation. Extensive research has been conducted to address precision medicine challenges using attention mechanism models such as SAN, GAT and transformers. Especially, the recent popularity of ChatGPT has significantly propelled the application of this model type to a new height. Therefore, I propose a Special Issue for Briefings in Bioinformatics about the topic 'Attention Mechanism Models for Precision Medicine'. This Special Issue aims to provide a comprehensive overview and presentation of innovative researches on the application of graph attention mechanism models in precision medicine.

GAPS: a geometric attention-based network for peptide binding site identification by the transfer learning approach.

Protein-peptide interactions (PPepIs) are vital to understanding cellular functions, which can facilitate the design of novel drugs. As an essential component in forming a PPepI, protein-peptide binding sites are the basis for understanding the mechanisms involved in PPepIs. Therefore, accurately identifying protein-peptide binding sites becomes a critical task. The traditional experimental methods for researching these binding sites are labor-intensive and time-consuming, and some computational tools have been invented to supplement it. However, these computational tools have limitations in generality or accuracy due to the need for ligand information, complex feature construction, or their reliance on modeling based on amino acid residues. To deal with the drawbacks of these computational algorithms, we describe a geometric attention-based network for peptide binding site identification (GAPS) in this work. The proposed model utilizes geometric feature engineering to construct atom representations and incorporates multiple attention mechanisms to update relevant biological features. In addition, the transfer learning strategy is implemented for leveraging the protein-protein binding sites information to enhance the protein-peptide binding sites recognition capability, taking into account the common structure and biological bias between proteins and peptides. Consequently, GAPS demonstrates the state-of-the-art performance and excellent robustness in this task. Moreover, our model exhibits exceptional performance across several extended experiments including predicting the apo protein-peptide, protein-cyclic peptide and the AlphaFold-predicted protein-peptide binding sites. These results confirm that the GAPS model is a powerful, versatile, stable method suitable for diverse binding site predictions.

Deletion variants calling in third-generation sequencing data based on a dual-attention mechanism.

Deletion is a crucial type of genomic structural variation and is associated with numerous genetic diseases. The advent of third-generation sequencing technology has facilitated the analysis of complex genomic structures and the elucidation of the mechanisms underlying phenotypic changes and disease onset due to genomic variants. Importantly, it has introduced innovative perspectives for deletion variants calling. Here we propose a method named Dual Attention Structural Variation (DASV) to analyze deletion structural variations in sequencing data. DASV converts gene alignment information into images and integrates them with genomic sequencing data through a dual attention mechanism. Subsequently, it employs a multi-scale network to precisely identify deletion regions. Compared with four widely used genome structural variation calling tools: cuteSV, SVIM, Sniffles and PBSV, the results demonstrate that DASV consistently achieves a balance between precision and recall, enhancing the F1 score across various datasets. The source code is available at https://github.com/deconvolution-w/DASV.

Recognition of rare antinuclear antibody patterns based on a novel attention-based enhancement framework.

Rare antinuclear antibody (ANA) pattern recognition has been a widely applied technology for routine ANA screening in clinical laboratories. In recent years, the application of deep learning methods in recognizing ANA patterns has witnessed remarkable advancements. However, the majority of studies in this field have primarily focused on the classification of the most common ANA patterns, while another subset has concentrated on the detection of mitotic metaphase cells. To date, no prior research has been specifically dedicated to the identification of rare ANA patterns. In the present paper, we introduce a novel attention-based enhancement framework, which was designed for the recognition of rare ANA patterns in ANA-indirect immunofluorescence images. More specifically, we selected the algorithm with the best performance as our target detection network by conducting comparative experiments. We then further developed and enhanced the chosen algorithm through a series of optimizations. Then, attention mechanism was introduced to facilitate neural networks in expediting the learning process, extracting more essential and distinctive features for the target features that belong to the specific patterns. The proposed approach has helped to obtained high precision rate of 86.40%, 82.75% recall, 84.24% F1 score and 84.64% mean average precision for a 9-category rare ANA pattern detection task on our dataset. Finally, we evaluated the potential of the model as medical technologist assistant and observed that the technologist's performance improved after referring to the results of the model prediction. These promising results highlighted its potential as an efficient and reliable tool to assist medical technologists in their clinical practice.

ADH-Enhancer: an attention-based deep hybrid framework for enhancer identification and strength prediction.

Enhancers play an important role in the process of gene expression regulation. In DNA sequence abundance or absence of enhancers and irregularities in the strength of enhancers affects gene expression process that leads to the initiation and propagation of diverse types of genetic diseases such as hemophilia, bladder cancer, diabetes and congenital disorders. Enhancer identification and strength prediction through experimental approaches is expensive, time-consuming and error-prone. To accelerate and expedite the research related to enhancers identification and strength prediction, around 19 computational frameworks have been proposed. These frameworks used machine and deep learning methods that take raw DNA sequences and predict enhancer's presence and strength. However, these frameworks still lack in performance and are not useful in real time analysis. This paper presents a novel deep learning framework that uses language modeling strategies for transforming DNA sequences into statistical feature space. It applies transfer learning by training a language model in an unsupervised fashion by predicting a group of nucleotides also known as k-mers based on the context of existing k-mers in a sequence. At the classification stage, it presents a novel classifier that reaps the benefits of two different architectures: convolutional neural network and attention mechanism. The proposed framework is evaluated over the enhancer identification benchmark dataset where it outperforms the existing best-performing framework by 5%, and 9% in terms of accuracy and MCC. Similarly, when evaluated over the enhancer strength prediction benchmark dataset, it outperforms the existing best-performing framework by 4%, and 7% in terms of accuracy and MCC.

scAMAC: self-supervised clustering of scRNA-seq data based on adaptive multi-scale autoencoder.

Cluster assignment is vital to analyzing single-cell RNA sequencing (scRNA-seq) data to understand high-level biological processes. Deep learning-based clustering methods have recently been widely used in scRNA-seq data analysis. However, existing deep models often overlook the interconnections and interactions among network layers, leading to the loss of structural information within the network layers. Herein, we develop a new self-supervised clustering method based on an adaptive multi-scale autoencoder, called scAMAC. The self-supervised clustering network utilizes the Multi-Scale Attention mechanism to fuse the feature information from the encoder, hidden and decoder layers of the multi-scale autoencoder, which enables the exploration of cellular correlations within the same scale and captures deep features across different scales. The self-supervised clustering network calculates the membership matrix using the fused latent features and optimizes the clustering network based on the membership matrix. scAMAC employs an adaptive feedback mechanism to supervise the parameter updates of the multi-scale autoencoder, obtaining a more effective representation of cell features. scAMAC not only enables cell clustering but also performs data reconstruction through the decoding layer. Through extensive experiments, we demonstrate that scAMAC is superior to several advanced clustering and imputation methods in both data clustering and reconstruction. In addition, scAMAC is beneficial for downstream analysis, such as cell trajectory inference. Our scAMAC model codes are freely available at https://github.com/yancy2024/scAMAC.

PUTransGCN: identification of piRNA-disease associations based on attention encoding graph convolutional network and positive unlabelled learning.

Piwi-interacting RNAs (piRNAs) play a crucial role in various biological processes and are implicated in disease. Consequently, there is an escalating demand for computational tools to predict piRNA-disease interactions. Although there have been computational methods proposed for the detection of piRNA-disease associations, the problem of imbalanced and sparse dataset has brought great challenges to capture the complex relationships between piRNAs and diseases. In response to this necessity, we have developed a novel computational architecture, denoted as PUTransGCN, which uses heterogeneous graph convolutional networks to uncover potential piRNA-disease associations. Additionally, the attention mechanism was used to adjust the weight parameters of aggregation heterogeneous node features automatically. For tackling the imbalanced dataset problem, the combined positive unlabelled learning (PUL) method comprising PU bagging, two-step and spy technique was applied to select reliable negative associations. The features of piRNAs and diseases were derived from three distinct biological sources by PUTransGCN, including information on piRNA sequences, semantic terms related to diseases and the existing network of piRNA-disease associations. In the experiment, PUTransGCN performs in 5-fold cross-validation with an AUC of 0.93 and 0.95 on two datasets, respectively, which outperforms the other six state-of-the-art models. We compared three different PUL methods, and the results of the ablation experiment indicate that the combined PUL method yields the best results. The PUTransGCN could serve as a valuable piRNA-disease prediction tool for upcoming studies in the biomedical field. The code for PUTransGCN is available at https://github.com/chenqiuhao/PUTransGCN.

DeepKEGG: a multi-omics data integration framework with biological insights for cancer recurrence prediction and biomarker discovery.

Deep learning-based multi-omics data integration methods have the capability to reveal the mechanisms of cancer development, discover cancer biomarkers and identify pathogenic targets. However, current methods ignore the potential correlations between samples in integrating multi-omics data. In addition, providing accurate biological explanations still poses significant challenges due to the complexity of deep learning models. Therefore, there is an urgent need for a deep learning-based multi-omics integration method to explore the potential correlations between samples and provide model interpretability. Herein, we propose a novel interpretable multi-omics data integration method (DeepKEGG) for cancer recurrence prediction and biomarker discovery. In DeepKEGG, a biological hierarchical module is designed for local connections of neuron nodes and model interpretability based on the biological relationship between genes/miRNAs and pathways. In addition, a pathway self-attention module is constructed to explore the correlation between different samples and generate the potential pathway feature representation for enhancing the prediction performance of the model. Lastly, an attribution-based feature importance calculation method is utilized to discover biomarkers related to cancer recurrence and provide a biological interpretation of the model. Experimental results demonstrate that DeepKEGG outperforms other state-of-the-art methods in 5-fold cross validation. Furthermore, case studies also indicate that DeepKEGG serves as an effective tool for biomarker discovery. The code is available at https://github.com/lanbiolab/DeepKEGG.

MUSCLE: multi-view and multi-scale attentional feature fusion for microRNA-disease associations prediction.

MicroRNAs (miRNAs) synergize with various biomolecules in human cells resulting in diverse functions in regulating a wide range of biological processes. Predicting potential disease-associated miRNAs as valuable biomarkers contributes to the treatment of human diseases. However, few previous methods take a holistic perspective and only concentrate on isolated miRNA and disease objects, thereby ignoring that human cells are responsible for multiple relationships. In this work, we first constructed a multi-view graph based on the relationships between miRNAs and various biomolecules, and then utilized graph attention neural network to learn the graph topology features of miRNAs and diseases for each view. Next, we added an attention mechanism again, and developed a multi-scale feature fusion module, aiming to determine the optimal fusion results for the multi-view topology features of miRNAs and diseases. In addition, the prior attribute knowledge of miRNAs and diseases was simultaneously added to achieve better prediction results and solve the cold start problem. Finally, the learned miRNA and disease representations were then concatenated and fed into a multi-layer perceptron for end-to-end training and predicting potential miRNA-disease associations. To assess the efficacy of our model (called MUSCLE), we performed 5- and 10-fold cross-validation (CV), which got average the Area under ROC curves of 0.966${\pm }$0.0102 and 0.973${\pm }$0.0135, respectively, outperforming most current state-of-the-art models. We then examined the impact of crucial parameters on prediction performance and performed ablation experiments on the feature combination and model architecture. Furthermore, the case studies about colon cancer, lung cancer and breast cancer also fully demonstrate the good inductive capability of MUSCLE. Our data and code are free available at a public GitHub repository: https://github.com/zht-code/MUSCLE.git.

EGPDI: identifying protein-DNA binding sites based on multi-view graph embedding fusion.

Mechanisms of protein-DNA interactions are involved in a wide range of biological activities and processes. Accurately identifying binding sites between proteins and DNA is crucial for analyzing genetic material, exploring protein functions, and designing novel drugs. In recent years, several computational methods have been proposed as alternatives to time-consuming and expensive traditional experiments. However, accurately predicting protein-DNA binding sites still remains a challenge. Existing computational methods often rely on handcrafted features and a single-model architecture, leaving room for improvement. We propose a novel computational method, called EGPDI, based on multi-view graph embedding fusion. This approach involves the integration of Equivariant Graph Neural Networks (EGNN) and Graph Convolutional Networks II (GCNII), independently configured to profoundly mine the global and local node embedding representations. An advanced gated multi-head attention mechanism is subsequently employed to capture the attention weights of the dual embedding representations, thereby facilitating the integration of node features. Besides, extra node features from protein language models are introduced to provide more structural information. To our knowledge, this is the first time that multi-view graph embedding fusion has been applied to the task of protein-DNA binding site prediction. The results of five-fold cross-validation and independent testing demonstrate that EGPDI outperforms state-of-the-art methods. Further comparative experiments and case studies also verify the superiority and generalization ability of EGPDI.

DeepFormer: a hybrid network based on convolutional neural network and flow-attention mechanism for identifying the function of DNA sequences.

Identifying the function of DNA sequences accurately is an essential and challenging task in the genomic field. Until now, deep learning has been widely used in the functional analysis of DNA sequences, including DeepSEA, DanQ, DeepATT and TBiNet. However, these methods have the problems of high computational complexity and not fully considering the distant interactions among chromatin features, thus affecting the prediction accuracy. In this work, we propose a hybrid deep neural network model, called DeepFormer, based on convolutional neural network (CNN) and flow-attention mechanism for DNA sequence function prediction. In DeepFormer, the CNN is used to capture the local features of DNA sequences as well as important motifs. Based on the conservation law of flow network, the flow-attention mechanism can capture more distal interactions among sequence features with linear time complexity. We compare DeepFormer with the above four kinds of classical methods using the commonly used dataset of 919 chromatin features of nearly 4.9 million noncoding DNA sequences. Experimental results show that DeepFormer significantly outperforms four kinds of methods, with an average recall rate at least 7.058% higher than other methods. Furthermore, we confirmed the effectiveness of DeepFormer in capturing functional variation using Alzheimer's disease, pathogenic mutations in alpha-thalassemia and modification in CCCTC-binding factor (CTCF) activity. We further predicted the maize chromatin accessibility of five tissues and validated the generalization of DeepFormer. The average recall rate of DeepFormer exceeds the classical methods by at least 1.54%, demonstrating strong robustness.

DeepAlgPro: an interpretable deep neural network model for predicting allergenic proteins.

Allergies have become an emerging public health problem worldwide. The most effective way to prevent allergies is to find the causative allergen at the source and avoid re-exposure. However, most of the current computational methods used to identify allergens were based on homology or conventional machine learning methods, which were inefficient and still had room to be improved for the detection of allergens with low homology. In addition, few methods based on deep learning were reported, although deep learning has been successfully applied to several tasks in protein sequence analysis. In the present work, a deep neural network-based model, called DeepAlgPro, was proposed to identify allergens. We showed its great accuracy and applicability to large-scale forecasts by comparing it to other available tools. Additionally, we used ablation experiments to demonstrate the critical importance of the convolutional module in our model. Moreover, further analyses showed that epitope features contributed to model decision-making, thus improving the model's interpretability. Finally, we found that DeepAlgPro was capable of detecting potential new allergens. Overall, DeepAlgPro can serve as powerful software for identifying allergens.

High-accuracy protein model quality assessment using attention graph neural networks.

Great improvement has been brought to protein tertiary structure prediction through deep learning. It is important but very challenging to accurately rank and score decoy structures predicted by different models. CASP14 results show that existing quality assessment (QA) approaches lag behind the development of protein structure prediction methods, where almost all existing QA models degrade in accuracy when the target is a decoy of high quality. How to give an accurate assessment to high-accuracy decoys is particularly useful with the available of accurate structure prediction methods. Here we propose a fast and effective single-model QA method, QATEN, which can evaluate decoys only by their topological characteristics and atomic types. Our model uses graph neural networks and attention mechanisms to evaluate global and amino acid level scores, and uses specific loss functions to constrain the network to focus more on high-precision decoys and protein domains. On the CASP14 evaluation decoys, QATEN performs better than other QA models under all correlation coefficients when targeting average LDDT. QATEN shows promising performance when considering only high-accuracy decoys. Compared to the embedded evaluation modules of predicted ${C}_{\alpha^{-}} RMSD$ (pRMSD) in RosettaFold and predicted LDDT (pLDDT) in AlphaFold2, QATEN is complementary and capable of achieving better evaluation on some decoy structures generated by AlphaFold2 and RosettaFold. These results suggest that the new QATEN approach can be used as a reliable independent assessment algorithm for high-accuracy protein structure decoys.

Cooperation of local features and global representations by a dual-branch network for transcription factor binding sites prediction.

Interactions between DNA and transcription factors (TFs) play an essential role in understanding transcriptional regulation mechanisms and gene expression. Due to the large accumulation of training data and low expense, deep learning methods have shown huge potential in determining the specificity of TFs-DNA interactions. Convolutional network-based and self-attention network-based methods have been proposed for transcription factor binding sites (TFBSs) prediction. Convolutional operations are efficient to extract local features but easy to ignore global information, while self-attention mechanisms are expert in capturing long-distance dependencies but difficult to pay attention to local feature details. To discover comprehensive features for a given sequence as far as possible, we propose a Dual-branch model combining Self-Attention and Convolution, dubbed as DSAC, which fuses local features and global representations in an interactive way. In terms of features, convolution and self-attention contribute to feature extraction collaboratively, enhancing the representation learning. In terms of structure, a lightweight but efficient architecture of network is designed for the prediction, in particular, the dual-branch structure makes the convolution and the self-attention mechanism can be fully utilized to improve the predictive ability of our model. The experiment results on 165 ChIP-seq datasets show that DSAC obviously outperforms other five deep learning based methods and demonstrate that our model can effectively predict TFBSs based on sequence feature alone. The source code of DSAC is available at https://github.com/YuBinLab-QUST/DSAC/.

Predicting circRNA-drug sensitivity associations by learning multimodal networks using graph auto-encoders and attention mechanism.

Recent studies have shown that the expression of circRNAs would affect drug sensitivity of cells and thus significantly influence the efficacy of drugs. Traditional biomedical experiments to validate such relationships are time-consuming and costly. Therefore, developing effective computational methods to predict potential associations between circRNAs and drug sensitivity is an important and urgent task. In this study, we propose a novel method, called MNGACDA, to predict possible circRNA-drug sensitivity associations for further biomedical screening. First, MNGACDA uses multiple sources of information from circRNAs and drugs to construct multimodal networks. It then employs node-level attention graph auto-encoders to obtain low-dimensional embeddings for circRNAs and drugs from the multimodal networks. Finally, an inner product decoder is applied to predict the association scores between circRNAs and drug sensitivity based on the embedding representations of circRNAs and drugs. Extensive experimental results based on cross-validations show that MNGACDA outperforms six other state-of-the-art methods. Furthermore, excellent performance in case studies demonstrates that MNGACDA is an effective tool for predicting circRNA-drug sensitivity associations in real situations. These results confirm the reliable prediction ability of MNGACDA in revealing circRNA-drug sensitivity associations.

Predicting miRNA-disease associations based on lncRNA-miRNA interactions and graph convolution networks.

Increasing studies have proved that microRNAs (miRNAs) are critical biomarkers in the development of human complex diseases. Identifying disease-related miRNAs is beneficial to disease prevention, diagnosis and remedy. Based on the assumption that similar miRNAs tend to associate with similar diseases, various computational methods have been developed to predict novel miRNA-disease associations (MDAs). However, selecting proper features for similarity calculation is a challenging task because of data deficiencies in biomedical science. In this study, we propose a deep learning-based computational method named MAGCN to predict potential MDAs without using any similarity measurements. Our method predicts novel MDAs based on known lncRNA-miRNA interactions via graph convolution networks with multichannel attention mechanism and convolutional neural network combiner. Extensive experiments show that the average area under the receiver operating characteristic values obtained by our method under 2-fold, 5-fold and 10-fold cross-validations are 0.8994, 0.9032 and 0.9044, respectively. When compared with five state-of-the-art methods, MAGCN shows improvement in terms of prediction accuracy. In addition, we conduct case studies on three diseases to discover their related miRNAs, and find that all the top 50 predictions for all the three diseases have been supported by established databases. The comprehensive results demonstrate that our method is a reliable tool in detecting new disease-related miRNAs.

CapsNet-LDA: predicting lncRNA-disease associations using attention mechanism and capsule network based on multi-view data.

Cumulative studies have shown that many long non-coding RNAs (lncRNAs) are crucial in a number of diseases. Predicting potential lncRNA-disease associations (LDAs) can facilitate disease prevention, diagnosis and treatment. Therefore, it is vital to develop practical computational methods for LDA prediction. In this study, we propose a novel predictor named capsule network (CapsNet)-LDA for LDA prediction. CapsNet-LDA first uses a stacked autoencoder for acquiring the informative low-dimensional representations of the lncRNA-disease pairs under multiple views, then the attention mechanism is leveraged to implement an adaptive allocation of importance weights to them, and they are subsequently processed using a CapsNet-based architecture for predicting LDAs. Different from the conventional convolutional neural networks (CNNs) that have some restrictions with the usage of scalar neurons and pooling operations. the CapsNets use vector neurons instead of scalar neurons that have better robustness for the complex combination of features and they use dynamic routing processes for updating parameters. CapsNet-LDA is superior to other five state-of-the-art models on four benchmark datasets, four perturbed datasets and an independent test set in the comparison experiments, demonstrating that CapsNet-LDA has excellent performance and robustness against perturbation, as well as good generalization ability. The ablation studies verify the effectiveness of some modules of CapsNet-LDA. Moreover, the ability of multi-view data to improve performance is proven. Case studies further indicate that CapsNet-LDA can accurately predict novel LDAs for specific diseases.

SPRDA: a link prediction approach based on the structural perturbation to infer disease-associated Piwi-interacting RNAs.

piRNA and PIWI proteins have been confirmed for disease diagnosis and treatment as novel biomarkers due to its abnormal expression in various cancers. However, the current research is not strong enough to further clarify the functions of piRNA in cancer and its underlying mechanism. Therefore, how to provide large-scale and serious piRNA candidates for biological research has grown up to be a pressing issue. In this study, a novel computational model based on the structural perturbation method is proposed to predict potential disease-associated piRNAs, called SPRDA. Notably, SPRDA belongs to positive-unlabeled learning, which is unaffected by negative examples in contrast to previous approaches. In the 5-fold cross-validation, SPRDA shows high performance on the benchmark dataset piRDisease, with an AUC of 0.9529. Furthermore, the predictive performance of SPRDA for 10 diseases shows the robustness of the proposed method. Overall, the proposed approach can provide unique insights into the pathogenesis of the disease and will advance the field of oncology diagnosis and treatment.

DBGRU-SE: predicting drug-drug interactions based on double BiGRU and squeeze-and-excitation attention mechanism.

The prediction of drug-drug interactions (DDIs) is essential for the development and repositioning of new drugs. Meanwhile, they play a vital role in the fields of biopharmaceuticals, disease diagnosis and pharmacological treatment. This article proposes a new method called DBGRU-SE for predicting DDIs. Firstly, FP3 fingerprints, MACCS fingerprints, Pubchem fingerprints and 1D and 2D molecular descriptors are used to extract the feature information of the drugs. Secondly, Group Lasso is used to remove redundant features. Then, SMOTE-ENN is applied to balance the data to obtain the best feature vectors. Finally, the best feature vectors are fed into the classifier combining BiGRU and squeeze-and-excitation (SE) attention mechanisms to predict DDIs. After applying five-fold cross-validation, The ACC values of DBGRU-SE model on the two datasets are 97.51 and 94.98%, and the AUC are 99.60 and 98.85%, respectively. The results showed that DBGRU-SE had good predictive performance for drug-drug interactions.

MMSMAPlus: a multi-view multi-scale multi-attention embedding model for protein function prediction.

Protein is the most important component in organisms and plays an indispensable role in life activities. In recent years, a large number of intelligent methods have been proposed to predict protein function. These methods obtain different types of protein information, including sequence, structure and interaction network. Among them, protein sequences have gained significant attention where methods are investigated to extract the information from different views of features. However, how to fully exploit the views for effective protein sequence analysis remains a challenge. In this regard, we propose a multi-view, multi-scale and multi-attention deep neural model (MMSMA) for protein function prediction. First, MMSMA extracts multi-view features from protein sequences, including one-hot encoding features, evolutionary information features, deep semantic features and overlapping property features based on physiochemistry. Second, a specific multi-scale multi-attention deep network model (MSMA) is built for each view to realize the deep feature learning and preliminary classification. In MSMA, both multi-scale local patterns and long-range dependence from protein sequences can be captured. Third, a multi-view adaptive decision mechanism is developed to make a comprehensive decision based on the classification results of all the views. To further improve the prediction performance, an extended version of MMSMA, MMSMAPlus, is proposed to integrate homology-based protein prediction under the framework of multi-view deep neural model. Experimental results show that the MMSMAPlus has promising performance and is significantly superior to the state-of-the-art methods. The source code can be found at https://github.com/wzy-2020/MMSMAPlus.