Fast learning optimized prediction methodology for protein secondary structure prediction, relative solvent accessibility prediction and phosphorylation prediction

Computational methods are rapidly gaining importance in the field of structural biology, mostly due to the explosive progress in genome sequencing projects and the large disparity between the number of sequences and the number of structures. There has been an exponential growth in the number of available protein sequences and a slower growth in the number of structures. There is therefore an urgent need to develop computed structures and identify the functions of these sequences. Developing methods that will satisfy these needs both efficiently and accurately is of paramount importance for advances in many biomedical fields, for a better basic understanding of aberrant states of stress and disease, including drug discovery and discovery of biomarkers. Several aspects of secondary structure predictions and other protein structure-related predictions are investigated using different types of information such as data obtained from knowledge-based potentials derived from amino acids in protein sequences, physicochemical properties of amino acids and propensities of amino acids to appear at the ends of secondary structures. Investigating the performance of these secondary structure predictions by type of amino acid highlights some interesting aspects relating to the influences of the individual amino acid types on formation of secondary structures and points toward ways to make further gains. Other research areas include Relative Solvent Accessibility (RSA) predictions and predictions of phosphorylation sites, which is one of the Post-Translational Modification (PTM) sites in proteins. Protein secondary structures and other features of proteins are predicted efficiently, reliably, less expensively and more accurately. A novel method called Fast Learning Optimized PREDiction (FLOPRED) Methodology is proposed for predicting protein secondary structures and other features, using knowledge-based potentials, a Neural Network based Extreme Learning Machine (ELM) and advanced Particle Swarm Optimization (PSO) techniques that yield better and faster convergence to produce more accurate results. These techniques yield superior classification of secondary structures, with a training accuracy of 93.33% and a testing accuracy of 92.24% with a standard deviation of 0.48% obtained for a small group of 84 proteins. We have a Matthew\u27s correlation-coefficient ranging between 80.58% and 84.30% for these secondary structures. Accuracies for individual amino acids range between 83% and 92% with an average standard deviation between 0.3% and 2.9% for the 20 amino acids. On a larger set of 415 proteins, we obtain a testing accuracy of 86.5% with a standard deviation of 1.38%. These results are significantly higher than those found in the literature. Prediction of protein secondary structure based on amino acid sequence is a common technique used to predict its 3-D structure. Additional information such as the biophysical properties of the amino acids can help improve the results of secondary structure prediction. A database of protein physicochemical properties is used as features to encode protein sequences and this data is used for secondary structure prediction using FLOPRED. Preliminary studies using a Genetic Algorithm (GA) for feature selection, Principal Component Analysis (PCA) for feature reduction and FLOPRED for classification give promising results. Some amino acids appear more often at the ends of secondary structures than others. A preliminary study has indicated that secondary structure accuracy can be improved as much as 6% by including these effects for those residues present at the ends of alpha-helix, beta-strand and coil. A study on RSA prediction using ELM shows large gains in processing speed compared to using support vector machines for classification. This indicates that ELM yields a distinct advantage in terms of processing speed and performance for RSA. Additional gains in accuracies are possible when the more advanced FLOPRED algorithm and PSO optimization are implemented. Phosphorylation is a post-translational modification on proteins often controls and regulates their activities. It is an important mechanism for regulation. Phosphorylated sites are known to be present often in intrinsically disordered regions of proteins lacking unique tertiary structures, and thus less information is available about the structures of phosphorylated sites. It is important to be able to computationally predict phosphorylation sites in protein sequences obtained from mass-scale sequencing of genomes. Phosphorylation sites may aid in the determination of the functions of a protein and to better understanding the mechanisms of protein functions in healthy and diseased states. FLOPRED is used to model and predict experimentally determined phosphorylation sites in protein sequences. Our new PSO optimization included in FLOPRED enable the prediction of phosphorylation sites with higher accuracy and with better generalization. Our preliminary studies on 984 sequences demonstrate that this model can predict phosphorylation sites with a training accuracy of 92.53% , a testing accuracy 91.42% and Matthew\u27s correlation coefficient of 83.9%. In summary, secondary structure prediction, Relative Solvent Accessibility and phosphorylation site prediction have been carried out on multiple sets of data, encoded with a variety of information drawn from proteins and the physicochemical properties of their constituent amino acids. Improved and efficient algorithms called S-ELM and FLOPRED, which are based on Neural Networks and Particle Swarm Optimization are used for classifying and predicting protein sequences. Analysis of the results of these studies provide new and interesting insights into the influence of amino acids on secondary structure prediction. S-ELM and FLOPRED have also proven to be robust and efficient for predicting relative solvent accessibility of proteins and phosphorylation sites. These studies show that our method is robust and resilient and can be applied for a variety of purposes. It can be expected to yield higher classification accuracy and better generalization performance compared to previous methods

On Improving Generalization of CNN-Based Image Classification with Delineation Maps Using the CORF Push-Pull Inhibition Operator

Deployed image classification pipelines are typically dependent on the images captured in real-world environments. This means that images might be affected by different sources of perturbations (e.g. sensor noise in low-light environments). The main challenge arises by the fact that image quality directly impacts the reliability and consistency of classification tasks. This challenge has, hence, attracted wide interest within the computer vision communities. We propose a transformation step that attempts to enhance the generalization ability of CNN models in the presence of unseen noise in the test set. Concretely, the delineation maps of given images are determined using the CORF push-pull inhibition operator. Such an operation transforms an input image into a space that is more robust to noise before being processed by a CNN. We evaluated our approach on the Fashion MNIST data set with an AlexNet model. It turned out that the proposed CORF-augmented pipeline achieved comparable results on noise-free images to those of a conventional AlexNet classification model without CORF delineation maps, but it consistently achieved significantly superior performance on test images perturbed with different levels of Gaussian and uniform noise

Unveiling the frontiers of deep learning: innovations shaping diverse domains

Deep learning (DL) enables the development of computer models that are capable of learning, visualizing, optimizing, refining, and predicting data. In recent years, DL has been applied in a range of fields, including audio-visual data processing, agriculture, transportation prediction, natural language, biomedicine, disaster management, bioinformatics, drug design, genomics, face recognition, and ecology. To explore the current state of deep learning, it is necessary to investigate the latest developments and applications of deep learning in these disciplines. However, the literature is lacking in exploring the applications of deep learning in all potential sectors. This paper thus extensively investigates the potential applications of deep learning across all major fields of study as well as the associated benefits and challenges. As evidenced in the literature, DL exhibits accuracy in prediction and analysis, makes it a powerful computational tool, and has the ability to articulate itself and optimize, making it effective in processing data with no prior training. Given its independence from training data, deep learning necessitates massive amounts of data for effective analysis and processing, much like data volume. To handle the challenge of compiling huge amounts of medical, scientific, healthcare, and environmental data for use in deep learning, gated architectures like LSTMs and GRUs can be utilized. For multimodal learning, shared neurons in the neural network for all activities and specialized neurons for particular tasks are necessary.Comment: 64 pages, 3 figures, 3 table

Bioinformatics and Machine Learning for Cancer Biology

Cancer is a leading cause of death worldwide, claiming millions of lives each year. Cancer biology is an essential research field to understand how cancer develops, evolves, and responds to therapy. By taking advantage of a series of “omics” technologies (e.g., genomics, transcriptomics, and epigenomics), computational methods in bioinformatics and machine learning can help scientists and researchers to decipher the complexity of cancer heterogeneity, tumorigenesis, and anticancer drug discovery. Particularly, bioinformatics enables the systematic interrogation and analysis of cancer from various perspectives, including genetics, epigenetics, signaling networks, cellular behavior, clinical manifestation, and epidemiology. Moreover, thanks to the influx of next-generation sequencing (NGS) data in the postgenomic era and multiple landmark cancer-focused projects, such as The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), machine learning has a uniquely advantageous role in boosting data-driven cancer research and unraveling novel methods for the prognosis, prediction, and treatment of cancer

Learning Multimodal Structures in Computer Vision

A phenomenon or event can be received from various kinds of detectors or under different conditions. Each such acquisition framework is a modality of the phenomenon. Due to the relation between the modalities of multimodal phenomena, a single modality cannot fully describe the event of interest. Since several modalities report on the same event introduces new challenges comparing to the case of exploiting each modality separately. We are interested in designing new algorithmic tools to apply sensor fusion techniques in the particular signal representation of sparse coding which is a favorite methodology in signal processing, machine learning and statistics to represent data. This coding scheme is based on a machine learning technique and has been demonstrated to be capable of representing many modalities like natural images. We will consider situations where we are not only interested in support of the model to be sparse, but also to reflect a-priorily known knowledge about the application in hand. Our goal is to extract a discriminative representation of the multimodal data that leads to easily finding its essential characteristics in the subsequent analysis step, e.g., regression and classification. To be more precise, sparse coding is about representing signals as linear combinations of a small number of bases from a dictionary. The idea is to learn a dictionary that encodes intrinsic properties of the multimodal data in a decomposition coefficient vector that is favorable towards the maximal discriminatory power. We carefully design a multimodal representation framework to learn discriminative feature representations by fully exploiting, the modality-shared which is the information shared by various modalities, and modality-specific which is the information content of each modality individually. Plus, it automatically learns the weights for various feature components in a data-driven scheme. In other words, the physical interpretation of our learning framework is to fully exploit the correlated characteristics of the available modalities, while at the same time leverage the modality-specific character of each modality and change their corresponding weights for different parts of the feature in recognition

Artificial Intelligence Tools for Facial Expression Analysis.

Inner emotions show visibly upon the human face and are understood as a basic guide to an individual’s inner world. It is, therefore, possible to determine a person’s attitudes and the effects of others’ behaviour on their deeper feelings through examining facial expressions. In real world applications, machines that interact with people need strong facial expression recognition. This recognition is seen to hold advantages for varied applications in affective computing, advanced human-computer interaction, security, stress and depression analysis, robotic systems, and machine learning. This thesis starts by proposing a benchmark of dynamic versus static methods for facial Action Unit (AU) detection. AU activation is a set of local individual facial muscle parts that occur in unison constituting a natural facial expression event. Detecting AUs automatically can provide explicit benefits since it considers both static and dynamic facial features. For this research, AU occurrence activation detection was conducted by extracting features (static and dynamic) of both nominal hand-crafted and deep learning representation from each static image of a video. This confirmed the superior ability of a pretrained model that leaps in performance. Next, temporal modelling was investigated to detect the underlying temporal variation phases using supervised and unsupervised methods from dynamic sequences. During these processes, the importance of stacking dynamic on top of static was discovered in encoding deep features for learning temporal information when combining the spatial and temporal schemes simultaneously. Also, this study found that fusing both temporal and temporal features will give more long term temporal pattern information. Moreover, we hypothesised that using an unsupervised method would enable the leaching of invariant information from dynamic textures. Recently, fresh cutting-edge developments have been created by approaches based on Generative Adversarial Networks (GANs). In the second section of this thesis, we propose a model based on the adoption of an unsupervised DCGAN for the facial features’ extraction and classification to achieve the following: the creation of facial expression images under different arbitrary poses (frontal, multi-view, and in the wild), and the recognition of emotion categories and AUs, in an attempt to resolve the problem of recognising the static seven classes of emotion in the wild. Thorough experimentation with the proposed cross-database performance demonstrates that this approach can improve the generalization results. Additionally, we showed that the features learnt by the DCGAN process are poorly suited to encoding facial expressions when observed under multiple views, or when trained from a limited number of positive examples. Finally, this research focuses on disentangling identity from expression for facial expression recognition. A novel technique was implemented for emotion recognition from a single monocular image. A large-scale dataset (Face vid) was created from facial image videos which were rich in variations and distribution of facial dynamics, appearance, identities, expressions, and 3D poses. This dataset was used to train a DCNN (ResNet) to regress the expression parameters from a 3D Morphable Model jointly with a back-end classifier

Methods towards precision bioinformatics in single cell era

Single-cell technology offers unprecedented insight into the molecular landscape of individual cell and is transforming precision medicine. Key to the effective use of single-cell data for disease understanding is the analysis of such information through bioinformatics methods. In this thesis, we examine and address several challenges in single-cell bioinformatics methods for precision medicine. While most of current single-cell analytical tools employ statistical and machine learning methods, deep learning technology has gained tremendous success in computer science. Combined with ensemble learning, this further improve model performance. Through a review article (Cao et al., 2020), we share recent key developments in this area and their contribution to bioinformatics research. Bioinformatics tools often use simulation data to assess proposed methodologies, but evaluation of the quality of single-cell RNA-sequencing (scRNA-seq) data simulation tools is lacking. We develop a comprehensive framework, SimBench (Cao et al., 2021), that examines a range of aspects from data properties to the ability to maintain biological signals, scalability, and applicability. While individual patient understanding is the key to precision medicine, there is little consensus on the best ways to compress complex single-cell data into summary statistics that represent each individual. We present scFeatures (Cao et al., 2022b), an approach that creates interpretable molecular representations for individuals. Finally, in a case study using multiple COVID-19 scRNA-seq data, we utilise scFeatures to generate molecular characterisations of individuals and illustrate the impact of ensemble learning and deep learning on improving disease outcome prediction. Overall, this thesis addresses several gaps in precision bioinformatics in the single-cell field by highlighting research advances, developing methodologies, and illustrating practical uses through experimental datasets and case studies