Artificial neural network model for predicting membrane protein types

Membrane proteins can be classified among the following five types: (1) type I membrane protein. (2) type II membrane protein. (3) multipass transmembrane proteins. (4) lipid chain-anchored membrane proteins, and (5) GPI-anchored membrane proteins. T. Kohonen's self-organization model which is a typical neural network is applied for predicting the type of a given membrane protein based on its amino acid composition. As a result, the high rates of self-consistency (94.80%) and cross-validation (77.76%), and stronger fault-tolerant ability were obtained.     

Enabling full-length evolutionary profiles based deep convolutional neural network for predicting DNA-binding proteins from sequence

Sequence based DNA-binding protein (DBP) prediction is a widely studied biological problem. Sliding windows on position specific substitution matrices (PSSMs) rows predict DNA-binding residues well on known DBPs but the same models cannot be applied to unequally sized protein sequences. PSSM summaries representing column averages and their amino-acid wise versions have been effectively used for the task, but it remains unclear if these features carry all the PSSM's predictive power, traditionally harnessed for binding site predictions. Here we evaluate if PSSMs scaled up to a fixed size by zero-vector padding (pPSSM) could perform better than the summary based features on similar models. Using multilayer perceptron (MLP) and deep convolutional neural network (CNN), we found that (a) Summary features work well for single-genome (human-only) data but are outperformed by pPSSM for diverse PDB-derived data sets, suggesting greater summary-level redundancy in the former, (b) even when summary features work comparably well with pPSSM, a consensus on the two outperforms both of them (c) CNN models comprehensively outperform their corresponding MLP models and (d) actual predicted scores from different models depend on the choice of input feature sets used whereas overall performance levels are model-dependent in which CNN leads the accuracy.     

ProDCoNN: Protein design using a convolutional neural network

Designing protein sequences that fold to a given three-dimensional (3D) structure has long been a challenging problem in computational structural biology with significant theoretical and practical implications. In this study, we first formulated this problem as predicting the residue type given the 3D structural environment around the C _α atom of a residue, which is repeated for each residue of a protein. We designed a nine-layer 3D deep convolutional neural network (CNN) that takes as input a gridded box with the atomic coordinates and types around a residue. Several CNN layers were designed to capture structure information at different scales, such as bond lengths, bond angles, torsion angles, and secondary structures. Trained on a very large number of protein structures, the method, called ProDCoNN (protein design with CNN), achieved state-of-the-art performance when tested on large numbers of test proteins and benchmark datasets.     

基于三维卷积神经网络的肺结节探测与定位方法

提出一种基于三维卷积神经网络对肺部计算机断层扫描图像(CT)进行肺结节自动探测及定位的方法.基于开源数据集LUNA16开展研究,对数据进行像素归一化、坐标转换等预处理,对正样本使用随机平移、旋转和翻转的方式进行扩充,对负样本进行随机采样.搭建了三维卷积神经网络并在训练过程中调整网络参数,直到得到性能最佳的网络.此外还设...     

A neural network for predicting the stability of DNA/DNA duplexes

A back-propagation neural network method has been developed to predict the stability of DNA/DNA duplexes. Calculated Tm with the present parameters fits the experimental values within reasonable errors (AD = 1.86 K, SEP = 1.99151, R2 = 0.9894 for NN1; AD = 1.59667 K, SEP = 2.03824, R2 = 0.99371 for NN2) and it has the advantage that the determinations of thermodynamic parameters are not needed.     

EditPredict: Prediction of RNA editable sites with convolutional neural network

RNA editing exerts critical impacts on numerous biological processes. While millions of RNA editings have been identified in humans, much more are expected to be discovered. In this work, we constructed Convolutional Neural Network (CNN) models to predict human RNA editing events in both Alu regions and non-Alu regions. With a validation dataset resulting from CRISPR/Cas9 knockout of the ADAR1 enzyme, the validation accuracies reached 99.5% and 93.6% for Alu and non-Alu regions, respectively. We ported our CNN models in a web service named EditPredict. EditPredict not only works on reference genome sequences but can also take into consideration single nucleotide variants in personal genomes. In addition to the human genome, EditPredict tackles other model organisms including bumblebee, fruitfly, mouse, and squid genomes. EditPredict can be used stand-alone to predict novel RNA editing and it can be used to assist in filtering for candidate RNA editing detected from RNA-Seq data.     

A convolutional neural network to recognize Chagas disease vectors using mobile phone images

There are several identification tools that can assist researchers, technicians and the community in the recognition of Chagas vector insects (triatomines), from other insects with similar morphologies. They involve using dichotomous keys, field guides, expert knowledge or, in more recent approaches, through the classification by a neural network of high quality photographs taken in standardized conditions. The aim of this research was to develop a deep neural network to recognize triatomines (insects associated with vectorial transmission of Chagas disease) directly from photos taken with any commonly available mobile device, without any other specialized equipment. To overcome the shortcomings of taking images using specific instruments and a controlled environment an innovative machine-learning approach was used: Fastai with Pytorch, a combination of open-source software for deep learning. The Convolutional Neural Network (CNN) was trained with triatomine photos, reaching a correct identification in 94.3% of the cases. Results were validated using photos sent by citizen scientists from the GeoVin project, resulting in 91.4% of correct identification of triatomines. The CNN provides a lightweight, robust method that even works with blurred images, poor lighting and even with the presence of other subjects and objects in the same frame. Future steps include the inclusion of the CNN into the framework of the GeoVin science project, which will also allow to further train the network using the photos sent by the citizen scientists. This would allow the participation of the community in the identification and monitoring of the vector insects, particularly in regions where government-led monitoring programmes are not frequent due to their low accessibility and high costs.     

基于卷积神经网络的细菌转录终止子预测

在遗传学中,终止子是位于poly(A)位点下游、长度在数百碱基以内、包含多个回文序列、具有终止转录功能的DNA结构域,其主要作用是使转录终止。在原核生物基因组中有两类转录终止子,即Rho-dependent因子和Rho-independent因子。在本项研究中,提出了一种新的预测模型(TermCNN)来快速准确地识别细菌转录终止子。该模型将具有代表性的6-mer特征子集(2 537个特征)和电子—离子相互作用伪电位(EIIP)作为输入向量,利用卷积神经网络(CNN)构建预测模型。五折交叉验证和独立测试的结果表明该模型优于最新的预测模型iTerm-PseKNC。值得注意的是,该模型在跨物种试验中具有明显的优势。它可以高度精确地预测大肠杆菌(E. coli)和枯草芽孢杆菌(B. subtilis)的转录终止子。     

Double-flow convolutional neural network for rapid large field of view Fourier ptychographic reconstruction

Fourier ptychographic microscopy is a promising imaging technique which can circumvent the space-bandwidth product of the system and achieve a reconstruction result with wide field-of-view (FOV), high-resolution and quantitative phase information. However, traditional iterative-based methods typically require multiple times to get convergence, and due to the wave vector deviation in different areas, the millimeter-level full-FOV cannot be well reconstructed once and typically required to be separated into several portions with sufficient overlaps and reconstructed separately, which makes traditional methods suffer from long reconstruction time for a large-FOV (of the order of minutes) and limits the application in real-time large-FOV monitoring of live sample in vitro. Here we propose a novel deep-learning based method called DFNN which can be used in place of traditional iterative-based methods to increase the quality of single large-FOV reconstruction and reducing the processing time from 167.5 to 0.1125 second. In addition, we demonstrate that by training based on the simulation dataset with high-entropy property (Opt. Express 28, 24 152 [2020]), DFNN could has fine generalizability and little dependence on the morphological features of samples. The superior robustness of DFNN against noise is also demonstrated in both simulation and experiment. Furthermore, our model shows more robustness against the wave vector deviation. Therefore, we could achieve better results at the edge areas of a single large-FOV reconstruction. Our method demonstrates a promising way to perform real-time single large-FOV reconstructions and provides further possibilities for real-time large-FOV monitoring of live samples with sub-cellular resolution.     

A neural network method for prediction of beta-turn types in proteins using evolutionary information

MOTIVATION: The prediction of beta-turns is an important element of protein secondary structure prediction. Recently, a highly accurate neural network based method Betatpred2 has been developed for predicting beta-turns in proteins using position-specific scoring matrices (PSSM) generated by PSI-BLAST and secondary structure information predicted by PSIPRED. However, the major limitation of Betatpred2 is that it predicts only beta-turn and non-beta-turn residues and does not provide any information of different beta-turn types. Thus, there is a need to predict beta-turn types using an approach based on multiple sequence alignment, which will be useful in overall tertiary structure prediction. RESULTS: In the present work, a method has been developed for the prediction of beta-turn types I, II, IV and VIII. For each turn type, two consecutive feed-forward back-propagation networks with a single hidden layer have been used where the first sequence-to-structure network has been trained on single sequences as well as on PSI-BLAST PSSM. The output from the first network along with PSIPRED predicted secondary structure has been used as input for the second-level structure-to-structure network. The networks have been trained and tested on a non-homologous dataset of 426 proteins chains by 7-fold cross-validation. It has been observed that the prediction performance for each turn type is improved significantly by using multiple sequence alignment. The performance has been further improved by using a second level structure-to-structure network and PSIPRED predicted secondary structure information. It has been observed that Type I and II beta-turns have better prediction performance than Type IV and VIII beta-turns. The final network yields an overall accuracy of 74.5, 93.5, 67.9 and 96.5% with MCC values of 0.29, 0.29, 0.23 and 0.02 for Type I, II, IV and VIII beta-turns, respectively, and is better than random prediction. AVAILABILITY: A web server for prediction of beta-turn types I, II, IV and VIII based on above approach is available at http://www.imtech.res.in/raghava/betaturns/ and http://bioinformatics.uams.edu/mirror/betaturns/ (mirror site).     

Artificial neural network method for predicting HIV protease cleavage sites in protein

Knowledge of the polyprotein cleavage sites by HIV protease will refine our understanding of its specificity, and the information thus acquired will be useful for designing specific and efficient HIV protease inhibitors. The search for inhibitors of HIV protease will be greatly expedited if one can find and accurate, robust, and rapid method for predicting the cleavage sites in proteins by HIV protease. In this paper, Kohonen’s self-organization model, which uses typical artificial neural networks, is applied to predict the cleavability of oligopeptides by proteases with multiple and extended specificity subsites. We selected HIV-1 protease as the subject of study. We chose 299 oligopeptides for the training set, and another 63 oligopeptides for the test set. Because of its high rate of correct prediction (58/63=92.06%) and stronger fault-tolerant ability, the neural network method should be a useful technique for finding effective inhibitors of HIV protease, which is one of the targets in designing potential drugs against AIDS. The principle of the artificial neural network method can also be applied to analyzing the specificity of any multisubsite enzyme.     

Artificial neural network method for predicting HIV protease cleavage sites in protein

Knowledge of the polyprotein cleavage sites by HIV protease will refine our understanding of its specificity, and the information thus acquired will be useful for designing specific and efficient HIV protease inhibitors. The search for inhibitors of HIV protease will be greatly expedited if one can find and accurate, robust, and rapid method for predicting the cleavage sites in proteins by HIV protease. In this paper, Kohonen’s self-organization model, which uses typical artificial neural networks, is applied to predict the cleavability of oligopeptides by proteases with multiple and extended specificity subsites. We selected HIV-1 protease as the subject of study. We chose 299 oligopeptides for the training set, and another 63 oligopeptides for the test set. Because of its high rate of correct prediction (58/63=92.06%) and stronger fault-tolerant ability, the neural network method should be a useful technique for finding effective inhibitors of HIV protease, which is one of the targets in designing potential drugs against AIDS. The principle of the artificial neural network method can also be applied to analyzing the specificity of any multisubsite enzyme.     

A novel approach to predicting human ingress motion using an artificial neural network

Due to the increased availability of digital human models, the need for knowing human movement is important in product design process. If the human motion is derived rapidly as design parameters change, a developer could determine the optimal parameters. For example, the optimal design of the door panel of an automobile can be obtained for a human operator to conduct the easiest ingress and egress motion. However, acquiring motion data from existing methods provides only unrealistic motion or requires a great amount of time. This not only leads to an increased time consumption for a product development, but also causes inefficiency of the overall design process. To solve such problems, this research proposes an algorithm to rapidly and accurately predict full-body human motion using an artificial neural network (ANN) and a motion database, as the design parameters are varied. To achieve this goal, this study refers to the processes behind human motor learning procedures. According to the previous research, human generate new motion based on past motion experience when they encounter new environments. Based on this principle, we constructed a motion capture database. To construct the database, motion capture experiments were performed in various environments using an optical motion capture system. To generate full-body human motion using this data, a generalized regression neural network (GRNN) was used. The proposed algorithm not only guarantees rapid and accurate results but also overcomes the ambiguity of the human motion objective function, which has been pointed out as a limitation of optimization-based research. Statistical criteria were utilized to confirm the similarity between the generated motion and actual human motion. Our research provides the basis for a rapid motion prediction algorithm that can include a variety of environmental variables. This research contributes to an increase in the usability of digital human models, and it can be applied to various research fields.     

A neural network model based on the analogy with the immune system

The similarities between the immune system and the central nervous system lead to the formulation of an unorthodox neural network model. The similarities between the two systems are strong at the system level, but do not seem to be so striking at the level of the components. A new model of a neuron is therefore formulated, in order that the analogy can be used. The essential feature of the hypothetical neuron is that it exhibits hysteresis at the single neuron level. A network of N such neurons is modelled by an N-dimensional system of ordinary differential equations, which exhibits almost 2N attractors. The model has a property that resembles free will. A conjecture concerning how the network might learn stimulus-response behaviour is described. According to the conjecture, learning does not involve modifications of the strengths of synaptic connections. Instead, stimuli ("questions") selectively applied to the network by a "teacher" can be used to take the system to a region of the N-dimensional phase space where the network gives the desired stimulus-response behaviour. A key role for sleep in the learning process is suggested. The model for sleep leads to prediction that the variance in the rates of firing of the neurons associated with memory should increase during waking hours, and decrease during sleep.     

Discriminating lysosomal membrane protein types using dynamic neural network

This work presents a dynamic artificial neural network methodology, which classifies the proteins into their classes from their sequences alone: the lysosomal membrane protein classes and the various other membranes protein classes. In this paper, neural networks-based lysosomal-associated membrane protein type prediction system is proposed. Different protein sequence representations are fused to extract the features of a protein sequence, which includes seven feature sets; amino acid (AA) composition, sequence length, hydrophobic group, electronic group, sum of hydrophobicity, R-group, and dipeptide composition. To reduce the dimensionality of the large feature vector, we applied the principal component analysis. The probabilistic neural network, generalized regression neural network, and Elman regression neural network (RNN) are used as classifiers and compared with layer recurrent network (LRN), a dynamic network. The dynamic networks have memory, i.e. its output depends not only on the input but the previous outputs also. Thus, the accuracy of LRN classifier among all other artificial neural networks comes out to be the highest. The overall accuracy of jackknife cross-validation is 93.2% for the data-set. These predicted results suggest that the method can be effectively applied to discriminate lysosomal associated membrane proteins from other membrane proteins (Type-I, Outer membrane proteins, GPI-Anchored) and Globular proteins, and it also indicates that the protein sequence representation can better reflect the core feature of membrane proteins than the classical AA composition.     

Self-organizing neural network for modeling 3D QSAR of colchicinoids

A novel scheme for modeling 3D QSAR has been developed. A method involving multiple self-organizing neural network adjusted to be analyzed by the PLS (partial least squares) analysis was used to model 3D QSAR of the selected colchicinoids. The model obtained allows the identification of some structural determinants of the biological activity of compounds.     

Disease named entity recognition from biomedical literature using a novel convolutional neural network

Background

Automatic disease named entity recognition (DNER) is of utmost importance for development of more sophisticated BioNLP tools. However, most conventional CRF based DNER systems rely on well-designed features whose selection is labor intensive and time-consuming. Though most deep learning methods can solve NER problems with little feature engineering, they employ additional CRF layer to capture the correlation information between labels in neighborhoods which makes them much complicated.

Methods

In this paper, we propose a novel multiple label convolutional neural network (MCNN) based disease NER approach. In this approach, instead of the CRF layer, a multiple label strategy (MLS) first introduced by us, is employed. First, the character-level embedding, word-level embedding and lexicon feature embedding are concatenated. Then several convolutional layers are stacked over the concatenated embedding. Finally, MLS strategy is applied to the output layer to capture the correlation information between neighboring labels.

Results

As shown by the experimental results, MCNN can achieve the state-of-the-art performance on both NCBI and CDR corpora.

Conclusions

The proposed MCNN based disease NER method achieves the state-of-the-art performance with little feature engineering. And the experimental results show the MLS strategy’s effectiveness of capturing the correlation information between labels in the neighborhood.

     

Segmentation of organs-at-risk in cervical cancer CT images with a convolutional neural network

PurposeWe introduced and evaluated an end-to-end organs-at-risk (OARs) segmentation model that can provide accurate and consistent OARs segmentation results in much less time.MethodsWe collected 105 patients’ Computed Tomography (CT) scans that diagnosed locally advanced cervical cancer and treated with radiotherapy in one hospital. Seven organs, including the bladder, bone marrow, left femoral head, right femoral head, rectum, small intestine and spinal cord were defined as OARs. The annotated contours of the OARs previously delineated manually by the patient’s radiotherapy oncologist and confirmed by the professional committee consisted of eight experienced oncologists before the radiotherapy were used as the ground truth masks. A multi-class segmentation model based on U-Net was designed to fulfil the OARs segmentation task. The Dice Similarity Coefficient (DSC) and 95th Hausdorff Distance (HD) are used as quantitative evaluation metrics to evaluate the proposed method.ResultsThe mean DSC values of the proposed method are 0.924, 0.854, 0.906, 0.900, 0.791, 0.833 and 0.827 for the bladder, bone marrow, femoral head left, femoral head right, rectum, small intestine, and spinal cord, respectively. The mean HD values are 5.098, 1.993, 1.390, 1.435, 5.949, 5.281 and 3.269 for the above OARs respectively.ConclusionsOur proposed method can help reduce the inter-observer and intra-observer variability of manual OARs delineation and lessen oncologists’ efforts. The experimental results demonstrate that our model outperforms the benchmark U-Net model and the oncologists’ evaluations show that the segmentation results are highly acceptable to be used in radiation therapy planning.