PROSHIFT: protein chemical shift prediction using artificial neural networks

The importance of protein chemical shift values for the determination of three-dimensional protein structure has increased in recent years because of the large databases of protein structures with assigned chemical shift data. These databases have allowed the investigation of the quantitative relationship between chemical shift values obtained by liquid state NMR spectroscopy and the three-dimensional structure of proteins. A neural network was trained to predict the ¹H, ¹³C, and ¹⁵N of proteins using their three-dimensional structure as well as experimental conditions as input parameters. It achieves root mean square deviations of 0.3 ppm for hydrogen, 1.3 ppm for carbon, and 2.6 ppm for nitrogen chemical shifts. The model reflects important influences of the covalent structure as well as of the conformation not only for backbone atoms (as, e.g., the chemical shift index) but also for side-chain nuclei. For protein models with a RMSD smaller than 5 Å a correlation of the RMSD and the r.m.s. deviation between the predicted and the experimental chemical shift is obtained. Thus the method has the potential to not only support the assignment process of proteins but also help with the validation and the refinement of three-dimensional structural proposals. It is freely available for academic users at the PROSHIFT server: www.jens-meiler.de/proshift.html     

Pruning artificial neural networks using neural complexity measures

This paper describes a new method for pruning artificial neural networks, using a measure of the neural complexity of the neural network. This measure is used to determine the connections that should be pruned. The measure computes the information-theoretic complexity of a neural network, which is similar to, yet different from previous research on pruning. The method proposed here shows how overly large and complex networks can be reduced in size, whilst retaining learnt behaviour and fitness. The technique proposed here helps to discover a network topology that matches the complexity of the problem it is meant to solve. This novel pruning technique is tested in a robot control domain, simulating a racecar. It is shown, that the proposed pruning method is a significant improvement over the most commonly used pruning method Magnitude Based Pruning. Furthermore, some of the pruned networks prove to be faster learners than the benchmark network that they originate from. This means that this pruning method can also help to unleash hidden potential in a network, because the learning time decreases substantially for a pruned a network, due to the reduction of dimensionality of the network.     

Anti-glycated activity prediction of polysaccharides from two guava fruits using artificial neural networks

High-efficiency ultrasonic treatment was used to extract the polysaccharides of Psidium guajava (PPG) and Psidium littorale (PPL). The aims of this study were to compare polysaccharide activities from these two guavas, as well as to investigate the relationship between ultrasonic conditions and anti-glycated activity. A mathematical model of anti-glycated activity was constructed with the artificial neural network (ANN) toolbox of MATLAB software. Response surface plots showed the correlation between ultrasonic conditions and bioactivity. The optimal ultrasonic conditions of PPL for the highest anti-glycated activity were predicted to be 256 W, 60 °C, and 12 min, and the predicted activity was 42.2%. The predicted highest anti-glycated activity of PPG was 27.2% under its optimal predicted ultrasonic condition. The experimental result showed that PPG and PPL possessed anti-glycated and antioxidant activities, and those of PPL were greater. The experimental data also indicated that ANN had good prediction and optimization capability.     

Modeling of pain using artificial neural networks

In dealing with human nervous system, the sensation of pain is as sophisticated as other physiological phenomena. To obtain an acceptable model of the pain, physiology of the pain has been analysed in the present paper. Pain mechanisms are explained in block diagram representation form. Because of the nonlinear interactions existing among different sections in the diagram, artificial neural networks (ANNs) have been exploited. The basic patterns associated with chronic and acute pain have been collected and then used to obtain proper features for training the neural networks. Both static and dynamic representations of the ANNs were used in this regard. The trained networks then were employed to predict response of the body when it is exposed to special excitations. These excitations have not been used in the training phase and their behavior is interesting from the physiological view. Some of these predictions can be inferred from clinical experimentations. However, more clinical tests have to be accomplished for some of the predictions.     

Bioprocess model building using artificial neural networks

Artificial neural networks are made upon of highly interconnected layers of simple neuron-like nodes. The neurons act as non-linear processing elements within the network. An attractive property of artificial neural networks is that given the appropriate network topology, they are capable of learning and characterising non-linear functional relationships. Furthermore, the structure of the resulting neural network based process model may be considered generic, in the sense that little prior process knowledge is required in its determination. The methodology therefore provides a cost efficient and reliable process modelling technique. One area where such a technique could be useful is biotechnological systems. Here, for example, the use of a process model within an estimation scheme has long been considered an effective means of overcoming inherent on-line measurement problems. However, the development of an accurate process model is extremely time consuming and often results in a model of limited applicability. Artificial neural networks could therefore prove to be a useful model building tool when striving to improve bioprocess operability. Two large scale industrial fermentation systems have been considered as test cases; a fed-batch penicillin fermentation and a continuous mycelial fermentation. Both systems serve to demonstrate the utility, flexibility and potential of the artificial neural network approach to process modelling.     

Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks

The purpose of this study was to develop a method of classifying cancers to specific diagnostic categories based on their gene expression signatures using artificial neural networks (ANNs). We trained the ANNs using the small, round blue-cell tumors (SRBCTs) as a model. These cancers belong to four distinct diagnostic categories and often present diagnostic dilemmas in clinical practice. The ANNs correctly classified all samples and identified the genes most relevant to the classification. Expression of several of these genes has been reported in SRBCTs, but most have not been associated with these cancers. To test the ability of the trained ANN models to recognize SRBCTs, we analyzed additional blinded samples that were not previously used for the training procedure, and correctly classified them in all cases. This study demonstrates the potential applications of these methods for tumor diagnosis and the identification of candidate targets for therapy.     

Measuring context dependency in birdsong using artificial neural networks

Context dependency is a key feature in sequential structures of human language, which requires reference between words far apart in the produced sequence. Assessing how long the past context has an effect on the current status provides crucial information to understand the mechanism for complex sequential behaviors. Birdsongs serve as a representative model for studying the context dependency in sequential signals produced by non-human animals, while previous reports were upper-bounded by methodological limitations. Here, we newly estimated the context dependency in birdsongs in a more scalable way using a modern neural-network-based language model whose accessible context length is sufficiently long. The detected context dependency was beyond the order of traditional Markovian models of birdsong, but was consistent with previous experimental investigations. We also studied the relation between the assumed/auto-detected vocabulary size of birdsong (i.e., fine- vs. coarse-grained syllable classifications) and the context dependency. It turned out that the larger vocabulary (or the more fine-grained classification) is assumed, the shorter context dependency is detected.     

Prediction of fingers posture using artificial neural networks

Predicting the hand and fingers posture during grasping tasks is an important issue in the frame of biomechanics. In this paper, a technique based on neural networks is proposed to learn the inverse kinematics mapping between the fingertip 3D position and the corresponding joint angles. Finger movements are obtained by an instrumented glove and are mapped to a multichain model of the hand. From the fingertip desired position, the neural networks allow predicting the corresponding finger joint angles keeping the specific subject coordination patterns. Two sets of movements are considered in this study. The first one, the training set, consisting of free fingers movements is used to construct the mapping between fingertip position and joint angles. The second one, constructed for testing purposes, is composed of a sequence of grasping tasks of everyday-life objects. The maximal mean error between fingertip measured position and fingertip position obtained from simulated joint angles and forward kinematics is 0.99+/-0.76mm for the training set and 1.49+/-1.62mm for the test set. Also, the maximal RMS error of joint angles prediction is 2.85 degrees and 5.10 degrees for the training and test sets respectively, while the maximal mean joint angles prediction error is -0.11+/-4.34 degrees and -2.52+/-6.71 degrees for the training and test sets, respectively. Results relative to the learning and generalization capabilities of this architecture are also presented and discussed.     

Clustering proteins into families using artificial neural networks

An incorrect version of Figure 3 was published in the abovearticle, the corrected version is reproduced below.     

Creating artificial human genomes using generative neural networks

Generative models have shown breakthroughs in a wide spectrum of domains due to recent advancements in machine learning algorithms and increased computational power. Despite these impressive achievements, the ability of generative models to create realistic synthetic data is still under-exploited in genetics and absent from population genetics. Yet a known limitation in the field is the reduced access to many genetic databases due to concerns about violations of individual privacy, although they would provide a rich resource for data mining and integration towards advancing genetic studies. In this study, we demonstrated that deep generative adversarial networks (GANs) and restricted Boltzmann machines (RBMs) can be trained to learn the complex distributions of real genomic datasets and generate novel high-quality artificial genomes (AGs) with none to little privacy loss. We show that our generated AGs replicate characteristics of the source dataset such as allele frequencies, linkage disequilibrium, pairwise haplotype distances and population structure. Moreover, they can also inherit complex features such as signals of selection. To illustrate the promising outcomes of our method, we showed that imputation quality for low frequency alleles can be improved by data augmentation to reference panels with AGs and that the RBM latent space provides a relevant encoding of the data, hence allowing further exploration of the reference dataset and features for solving supervised tasks. Generative models and AGs have the potential to become valuable assets in genetic studies by providing a rich yet compact representation of existing genomes and high-quality, easy-access and anonymous alternatives for private databases.     

On-line prediction of fermentation variables using neural networks

This article presents an introduction to the use of neural network computational algorithms for the dynamic modeling of bioprocesses. The dynamic neural model is used for the prediction of key fermentation variables. This relatively hew method is compared with a more traditional prediction technique to judge its performance for prediction. Illustrative simulation results of a continuous stirred tank fermentor are used for this comparison. It is shown that neural network models are accurate with a certain degree of noise immunity. They offer the distinctive ability over more traditional methods to learn very naturally complex relationships without requiring the knowledge of the model structure.     

Genetic prediction of ICU hospitalization and mortality in COVID‐19 patients using artificial neural networks

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease‐19 (COVID‐19). We aimed to a) identify complement‐related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement‐related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID‐19. Through targeted next‐generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH‐related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID‐19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID‐19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID‐19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype.     

Locus minimization in breed prediction using artificial neural network approach

Molecular markers, viz. microsatellites and single nucleotide polymorphisms, have revolutionized breed identification through the use of small samples of biological tissue or germplasm, such as blood, carcass samples, embryos, ova and semen, that show no evident phenotype. Classical tools of molecular data analysis for breed identification have limitations, such as the unavailability of referral breed data, causing increased cost of collection each time, compromised computational accuracy and complexity of the methodology used. We report here the successful use of an artificial neural network (ANN) in background to decrease the cost of genotyping by locus minimization. The webserver is freely accessible ( http://nabg.iasri.res.in/bisgoat ) to the research community. We demonstrate that the machine learning (ANN) approach for breed identification is capable of multifold advantages such as locus minimization, leading to a drastic reduction in cost, and web availability of reference breed data, alleviating the need for repeated genotyping each time one investigates the identity of an unknown breed. To develop this model web implementation based on ANN, we used 51 850 samples of allelic data of microsatellite‐marker‐based DNA fingerprinting on 25 loci covering 22 registered goat breeds of India for training. Minimizing loci to up to nine loci through the use of a multilayer perceptron model, we achieved 96.63% training accuracy. This server can be an indispensable tool for identification of existing breeds and new synthetic commercial breeds, leading to protection of intellectual property in case of sovereignty and bio‐piracy disputes. This server can be widely used as a model for cost reduction by locus minimization for various other flora and fauna in terms of variety, breed and/or line identification, especially in conservation and improvement programs.     

Thrips (Thysanoptera) identification using artificial neural networks

We studied the use of a supervised artificial neural network (ANN) model for semi-automated identification of 18 common European species of Thysanoptera from four genera: Aeolothrips Haliday (Aeolothripidae), Chirothrips Haliday, Dendrothrips Uzel, and Limothrips Haliday (all Thripidae). As input data, we entered 17 continuous morphometric and two qualitative two-state characters measured or determined on different parts of the thrips body (head, pronotum, forewing and ovipositor) and the sex. Our experimental data set included 498 thrips specimens. A relatively simple ANN architecture (multilayer perceptrons with a single hidden layer) enabled a 97% correct simultaneous identification of both males and females of all the 18 species in an independent test. This high reliability of classification is promising for a wider application of ANN in the practice of Thysanoptera identification.     

Prediction of problematic wine fermentations using artificial neural networks

Artificial neural networks (ANNs) have been used for the recognition of non-linear patterns, a characteristic of bioprocesses like wine production. In this work, ANNs were tested to predict problems of wine fermentation. A database of about 20,000 data from industrial fermentations of Cabernet Sauvignon and 33 variables was used. Two different ways of inputting data into the model were studied, by points and by fermentation. Additionally, different sub-cases were studied by varying the predictor variables (total sugar, alcohol, glycerol, density, organic acids and nitrogen compounds) and the time of fermentation (72, 96 and 256 h). The input of data by fermentations gave better results than the input of data by points. In fact, it was possible to predict 100% of normal and problematic fermentations using three predictor variables: sugars, density and alcohol at 72 h (3 days). Overall, ANNs were capable of obtaining 80% of prediction using only one predictor variable at 72 h; however, it is recommended to add more fermentations to confirm this promising result.     

Modeling of phenol degradation system using artificial neural networks

Pseudomonas pictorum (NICM-2077) an effective strain used in the biodegradation of phenol was grown on various nutrient compounds which protect the microbes while confronting shock loads of concentrated toxic pollutants during waste water treatment. In the present study the effect of glucose, yeast extract, (NH₄)₂SO₄ and NaCl on phenol degradation has been investigated and a Artificial Neural Network (ANN) Model has been developed to predict degradation. Also the learning, recall and generalization characteristics of neural networks has been studied using phenol degradation system data. The network model was then compared with a Multiple Regression Analysis model (MRA) arrived from the same training data. Further, these two models were used to predict the percentage degradation of phenol for a blind test data. Though both the models perform equally well ANN is found to be better than MRA due to its slightly higher coefficient of correlation, lower RMS error value and lower average absolute error value during prediction.     

Prediction of N-linked glycan branching patterns using artificial neural networks

A model was developed for novel prediction of N-linked glycan branching pattern classification for CHO-derived N-linked glycoproteins. The model consists of 30 independent recurrent neural networks and uses predicted quantities of secondary structure elements and residue solvent accessibility as an input vector. The model was designed to predict the major component of a heterogeneous mixture of CHO-derived glycoforms of a recombinant protein under normal growth conditions. Resulting glycosylation prediction is classified as either complex-type or high mannose. The incorporation of predicted quantities in the input vector allowed for theoretical mutant N-linked glycan branching predictions without initial experimental analysis of protein structures. Primary amino acid sequence data were effectively eliminated from the input vector space based on neural network prediction analyses. This provided further evidence that localized protein secondary structure elements and conformational structure may play more important roles in determining glycan branching patterns than does the primary sequence of a polypeptide. A confidence interval parameter was incorporated into the model to enable identification of false predictions. The model was further tested using published experimental results for mutants of the tissue-type plasminogen activator protein [J. Wilhelm, S.G. Lee, N.K. Kalyan, S.M. Cheng, F. Wiener, W. Pierzchala, P.P. Hung, Alterations in the domain structure of tissue-type plasminogen activator change the nature of asparagine glycosylation. Biotechnology (N.Y.) 8 (1990) 321-325].     

Eye tracking using artificial neural networks for human computer interaction

This paper describes an ongoing project that has the aim to develop a low cost application to replace a computer mouse for people with physical impairment. The application is based on an eye tracking algorithm and assumes that the camera and the head position are fixed. Color tracking and template matching methods are used for pupil detection. Calibration is provided by neural networks as well as by parametric interpolation methods. Neural networks use back-propagation for learning and bipolar sigmoid function is chosen as the activation function. The user's eye is scanned with a simple web camera with backlight compensation which is attached to a head fixation device. Neural networks significantly outperform parametric interpolation techniques: 1) the calibration procedure is faster as they require less calibration marks and 2) cursor control is more precise. The system in its current stage of development is able to distinguish regions at least on the level of desktop icons. The main limitation of the proposed method is the lack of head-pose invariance and its relative sensitivity to illumination (especially to incidental pupil reflections).