Redundancy-weighting the PDB for detailed secondary structure prediction using deep-learning models

Most of the protein structure prediction methods use a multi-step process, which often includes secondary structure prediction, contact prediction, fragment generation, clustering, etc. For many years, secondary structure prediction has been the workhorse for numerous methods aimed at predicting protein structure and function. This paper presents a new mixed integer linear optimization (MILP)-based consensus method: a Consensus scheme based On a mixed integer liNear optimization method for seCOndary stRucture preDiction (CONCORD). Based on seven secondary structure prediction methods, SSpro, DSC, PROF, PROFphd, PSIPRED, Predator and GorIV, the MILP-based consensus method combines the strengths of different methods, maximizes the number of correctly predicted amino acids and achieves a better prediction accuracy. The method is shown to perform well compared with the seven individual methods when tested on the PDBselect25 training protein set using sixfold cross validation. It also performs well compared with another set of 10 online secondary structure prediction servers (including several recent ones) when tested on the CASP9 targets ( http://predictioncenter.org/casp9/ ). The average Q3 prediction accuracy is 83.04 per cent for the sixfold cross validation of the PDBselect25 set and 82.3 per cent for the CASP9 targets. We have developed a MILP-based consensus method for protein secondary structure prediction. A web server, CONCORD, is available to the scientific community at http://helios.princeton.edu/CONCORD .

The predictive limits of the amino acid composition for the secondary structural content (percentage of residues in the secondary structural states helix, sheet, and coil) in proteins are assessed quantitatively. For the first time, techniques for prediction of secondary structural content are presented which rely on the amino acid composition as the only information on the query protein. In our first method, the amino acid composition of an unknown protein is represented by the best (in a least square sense) linear combination of the characteristic amino acid compositions of the three secondary structural types computed from a learning set of tertiary structures. The second technique is a generalization of the first one and takes into account also possible compositional couplings between any two sorts of amino acids. Its mathematical formulation results in an eigenvalue/eigenvector problem of the second moment matrix describing the amino acid compositional fluctuations of secondary structural types in various proteins of a learning set. Possible correlations of the principal directions of the eigenspaces with physical properties of the amino acids were also checked. For example, the first two eigenvectors of the helical eigenspace correlate with the size and hydrophobicity of the residue types respectively. As learning and test sets of tertiary structures, we utilized representative, automatically generated subsets of Protein Data Bank (PDB) consisting of non-homologous protein structures at the resolution thresholds < or = 1.8A, < or = 2.0A, < or = 2.5A, and < or = 3.0 A. We show that the consideration of compositional couplings improves prediction accuracy, albeit not dramatically. Whereas in the self-consistency test (learning with the protein to be predicted), a clear decrease of prediction accuracy with worsening resolution is observed, the jackknife test (leave the predicted protein out) yielded best results for the largest dataset (< or = 3.0A, almost no difference to the self-consistency test!), i.e., only this set, with more than 400 proteins, is sufficient for stable computation of the parameters in the prediction function of the second method. The average absolute error in predicting the fraction of helix, sheet, and coil from amino acid composition of the query protein are 13.7, 12.6, and 11.4%, respectively with r.m.s. deviations in the range of 8.6 divided by 11.8% for the 3.0 A dataset in a jackknife test. The absolute precision of the average absolute errors is in the range of 1 divided by 3% as measured for other representative subsets of the PDB. Secondary structural content prediction methods found in the literature have been clustered in accordance with their prediction accuracies. To our surprise, much more complex secondary structure prediction methods utilized for the same purpose of secondary structural content prediction achieve prediction accuracies very similar to those of the present analytic techniques, implying that all the information beyond the amino acid composition is, in fact, mainly utilized for positioning the secondary structural state in the sequence but not for determination of the overall number of residues in a secondary structural type. This result implies that higher prediction accuracies cannot be achieved relying solely on the amino acid composition of an unknown query protein as prediction input. Our prediction program SSCP has been made available as a World Wide Web and E-mail service.

Prediction of protein secondary structure provides information that is useful for other prediction methods like fold recognition and ab initio 3D prediction. A consensus prediction constructed from the output of several methods should yield more reliable results than each of the individual methods. We present an approach that reveals subtle but systematic differences in the output of different secondary structure prediction methods allowing the derivation of coherent consensus predictions. The method uses a machine learning technique that builds decision trees from existing data. The first results of our analysis show that consensus prediction of protein secondary structure may be improved both quantitatively and qualitatively.

Protein secondary structure predictions and amino acid long range contact map predictions from primary sequence of proteins have been explored to aid in modelling protein tertiary structures. In order to evaluate the usefulness of secondary structure and 3D-residue contact prediction methods to model protein structures we have used the known Q3 (alpha-helix,beta-strands and irregular turns/loops) secondary structure information, along with residue-residue contact information as restraints for MODELLER. We present here results of our modelling studies on 30 best resolved single domain protein structures of varied lengths. The results shows that it is very difficult to obtain useful models even with 100% accurate secondary structure predictions and accurate residue contact predictions for up to 30% of residues in a sequence. The best models that we obtained for proteins of lengths 37, 70, 118, 136 and 193 amino acid residues are of RMSDs 4.17, 5.27, 9.12, 7.89 and 9.69,respectively. The results show that one can obtain better models for the proteins which have high percent of alpha-helix content. This analysis further shows that MODELLER restrain optimization program can be useful only if we have truly homologous structure(s) as a template where it derives numerous restraints, almost identical to the templates used. This analysis also clearly indicates that even if we satisfy several true residue-residue contact distances, up to 30%of their sequence length with fully known secondary structural information, we end up predicting model structures much distant from their corresponding native structures.

PurposeThe first transmission of coronavirus to humans started in Wuhan city of China, took the shape of a pandemic called Corona Virus Disease 2019 (COVID-19), and posed a principal threat to the entire world. The researchers are trying to inculcate artificial intelligence (Machine learning or deep learning models) for the efficient detection of COVID-19. This research explores all the existing machine learning (ML) or deep learning (DL) models, used for COVID-19 detection which may help the researcher to explore in different directions. The main purpose of this review article is to present a compact overview of the application of artificial intelligence to the research experts, helping them to explore the future scopes of improvement.MethodsThe researchers have used various machine learning, deep learning, and a combination of machine and deep learning models for extracting significant features and classifying various health conditions in COVID-19 patients. For this purpose, the researchers have utilized different image modalities such as CT-Scan, X-Ray, etc. This study has collected over 200 research papers from various repositories like Google Scholar, PubMed, Web of Science, etc. These research papers were passed through various levels of scrutiny and finally, 50 research articles were selected.ResultsIn those listed articles, the ML / DL models showed an accuracy of 99% and above while performing the classification of COVID-19. This study has also presented various clinical applications of various research. This study specifies the importance of various machine and deep learning models in the field of medical diagnosis and research.ConclusionIn conclusion, it is evident that ML/DL models have made significant progress in recent years, but there are still limitations that need to be addressed. Overfitting is one such limitation that can lead to incorrect predictions and overburdening of the models. The research community must continue to work towards finding ways to overcome these limitations and make machine and deep learning models even more effective and efficient. Through this ongoing research and development, we can expect even greater advances in the future.

Efforts to use computers in predicting the secondary structure of proteins based only on primary structure information started over a quarter century ago [1-3]. Although the results were encouraging initially, the accuracy of the pioneering methods generally did not attain the level required for using predictions of secondary structures reliably in modelling the three-dimensional topology of proteins. During the last decade, however, the introduction of new computational techniques as well as the use of multiple sequence information has lead to a dramatic increase in the success rate of prediction methods, such that successful 3D modelling based on predicted secondary structure has become feasible [e.g., Ref 4]. This review is aimed at presenting an overview of the scale of the secondary structure prediction problem and associated pitfalls, as well as the history of the development of computational prediction methods. As recent successful strategies for secondary structure prediction all rely on multiple sequence information, some methods for accurate protein multiple sequence alignments will also be described. While the main focus is on prediction methods for globular proteins, also the prediction of trans-membrane segments within membrane proteins will be briefly summarised. Finally, an integrated iterative approach tying secondary structure prediction and multiple alignment will be introduced [5].

COVID-19 is highly infectious and causes acute respiratory disease. Machine learning (ML) and deep learning (DL) models are vital in detecting disease from computerized chest tomography (CT) scans. The DL models outperformed the ML models. For COVID-19 detection from CT scan images, DL models are used as end-to-end models. Thus, the performance of the model is evaluated for the quality of the extracted feature and classification accuracy. There are four contributions included in this work. First, this research is motivated by studying the quality of the extracted feature from the DL by feeding these extracted to an ML model. In other words, we proposed comparing the end-to-end DL model performance against the approach of using DL for feature extraction and ML for the classification of COVID-19 CT scan images. Second, we proposed studying the effect of fusing extracted features from image descriptors, e.g., Scale-Invariant Feature Transform (SIFT), with extracted features from DL models. Third, we proposed a new Convolutional Neural Network (CNN) to be trained from scratch and then compared to the deep transfer learning on the same classification problem. Finally, we studied the performance gap between classic ML models against ensemble learning models. The proposed framework is evaluated using a CT dataset, where the obtained results are evaluated using five different metrics The obtained results revealed that using the proposed CNN model is better than using the well-known DL model for the purpose of feature extraction. Moreover, using a DL model for feature extraction and an ML model for the classification task achieved better results in comparison to using an end-to-end DL model for detecting COVID-19 CT scan images. Of note, the accuracy rate of the former method improved by using ensemble learning models instead of the classic ML models. The proposed method achieved the best accuracy rate of 99.39%.

Although most proteins conform to the classical one‐structure/one‐function paradigm, an increasing number of proteins with dual structures and functions have been discovered. In response to cellular stimuli, such proteins undergo structural changes sufficiently dramatic to remodel even their secondary structures and domain organization. This “fold‐switching” capability fosters protein multi‐functionality, enabling cells to establish tight control over various biochemical processes. Accurate predictions of fold‐switching proteins could both suggest underlying mechanisms for uncharacterized biological processes and reveal potential drug targets. Recently, we developed a prediction method for fold‐switching proteins using structure‐based thermodynamic calculations and discrepancies between predicted and experimentally determined protein secondary structure (Porter and Looger, Proc Natl Acad Sci U S A 2018; 115:5968–5973). Here we seek to leverage the negative information found in these secondary structure prediction discrepancies. To do this, we quantified secondary structure prediction accuracies of 192 known fold‐switching regions (FSRs) within solved protein structures found in the Protein Data Bank (PDB). We find that the secondary structure prediction accuracies for these FSRs vary widely. Inaccurate secondary structure predictions are strongly associated with fold‐switching proteins compared to equally long segments of non‐fold‐switching proteins selected at random. These inaccurate predictions are enriched in helix‐to‐strand and strand‐to‐coil discrepancies. Finally, we find that most proteins with inaccurate secondary structure predictions are underrepresented in the PDB compared with their alternatively folded cognates, suggesting that unequal representation of fold‐switching conformers within the PDB could be an important cause of inaccurate secondary structure predictions. These results demonstrate that inconsistent secondary structure predictions can serve as a useful preliminary marker of fold switching.

Coastal aquifers are vital for sustaining ecosystems and providing freshwater for agriculture and domestic use. However, rising groundwater salinity in these regions demands innovative approaches for accurate modeling and prediction. In recent decades, machine learning (ML) and deep learning (DL) techniques have been extensively used across various water resource management fields, often yielding promising outcomes. This review examines the growing usage of ML and DL techniques in modeling groundwater salinity in coastal aquifers. The analysis is based on 104 peer-reviewed journal articles including the review articles indexed in PubMed, ScienceDirect, Google Scholar, Scopus, and SpringerLink using keywords like "saltwater intrusion", "machine learning", “deep learning”, and "groundwater salinity". The review discusses recent advancements, challenges, and future directions for improving ML model accuracy and applicability. Studies reveal an increasing reliance on ML techniques to predict groundwater salinity and manage seawater intrusion across various coastal geological settings. Researchers have employed a range of ML models, from traditional methods like Artificial Neural Networks and Adaptive Neuro Fuzzy Inference Systems to advanced DL-based models like Convolutional Neural Networks and Long Short-Term Memory Networks, often using ensemble methods to enhance accuracy. Key findings include the top-tier output of ensemble and optimized models, including Random Forest and Grasshopper Optimization Algorithm-XGBoost. These studies highlight the importance of model selection, input variable ranking, and computational efficiency, demonstrating ML's global relevance in environmental management. The review highlights the prospects of ML, DL, and ensemble models to redefine groundwater management in coastal aquifers, offering more effective and sustainable solutions to the challenges posed by groundwater salinity and saltwater intrusion. Future advancements will focus on further integrating DL, explainable artificial intelligence, and ensemble approaches, along with other innovative techniques, to explore sparsely studied variables, model new or unique study areas, and apply ML methods for managing groundwater salinity.

Predicting protein secondary structure using a mixed-modal SVM method in a compound pyramid model

The Protein Data Bank (PDB) provides open access to &gt;180,000 biological macromolecules that facilitate understanding of the structure and its function in biology. wwPDB collaboration and expert biocuration is a key to provide the best-curated biological data resource. wwPDB biocurators are at the very front line of structural biology who bridge between the scientists who submit PDB structures and the public who use these data. Our ultimate goal is to support research, training, and education worldwide and facilitate public awareness and understanding of these scientific discoveries. The key to long-term success and sustainability is forming the wwPDB partnership. Currently we have 15 biocurators worldwide working at RCSB PDB, PDBe and PDBj. We maintain a single global archive, no matter which PDB site users download data files from, we ensure identical data files are provided. wwPDB biocurators use a unified OneDep system to curate data. This system provides geographical workload distribution. wwPDB Biocurators setup standard procedures and follow these practices to enforce data standardization among PDB partners. We also review PDB archive and bring the data up to modern standards by conducting remediation effort. Biocuration at wwPDB is important. We manage data deposition, quality, and integrity, and provide integral support to the research community worldwide. To ensure data are Findable, Accessible, Interoperable, and Reusable (FAIR), biocuration at wwPDB focuses on data standardization and quality control. For data standardization, each PDB entry is assigned a unique, persistent identifier, data files are brought to semantic integrity and a common format that can enable large-scale data analysis and distribution. For data quality control, we cross-check with external database references such as UniProt, NCBI, or PubMed. Whatever possible, metadata are conformed to controlled vocabularies and range limits are set to catch data outliers. At the deposition time, biocuration is provided by data depositors on the sequences and taxonomy for polymers and chemical information for ligands if ligands do not match to PDB Chemical Component Dictionary. After data submission, wwPDB biocurators cross-check author’s sequence/taxonomy with UNP/NCBI references, assign existing ligands or add new ligand definitions based on author provided information, provide secondary and quaternary structure as value-added annotation. More importantly, wwPDB biocurators validate structures against experimental data adopting community-recommended validation software and provide depositors an official validation report for their manuscript submission which is now required by many scientific journals. Throughout the COVID-19 pandemic, wwPDB biocuration staff have continued to support research, training and education worldwide. All biocurators have been working remotely since March 2019. The use of unified OneDep system makes this possible with easy transition. We have record high on number of depositions with SARS-CoV-2 structures accounted for 7% of 2020 depositions. For the benefit of global health, as the structural biology community stepped up to provide much-needed insights into SARS-CoV-2, wwPDB biocurators have prioritized SARS-CoV-2 structures and working with depositors closely to release their structures immediately. As of August 1 st 2021, more than 1400 SARS-CoV-2 structures are now freely available from the PDB, reflecting enormous efforts made by the structural biology community in fighting the pandemic. The first structure with PDB ID 6LU7 was deposited on January 26 th 2020 and quickly released in about one week. PDB has recently provided coordinate versioning to allow depositors of the record to update their released structures without change of PDB IDs. Occasionally, rapid PDB data deposition and publication of SARS-CoV-2 structures driven by an understandable sense of urgency has resulted errors in public released PDB structures. The wwPDB coordinate versioning feature has enabled rapid correction of SARS-CoV-2 related structures archived in the PDB. To make the data findable, SARS-CoV-2 structures were updated with standard molecular name, taxonomy, and EC number when UNP references became available.

Social media platforms provide valuable insights into mental health trends by capturing user-generated discussions on conditions such as depression, anxiety, and suicidal ideation. Machine learning (ML) and deep learning (DL) models have been increasingly applied to classify mental health conditions from textual data, but selecting the most effective model involves trade-offs in accuracy, interpretability, and computational efficiency. This study evaluates multiple ML models, including logistic regression, random forest, and LightGBM, alongside DL architectures such as ALBERT and Gated Recurrent Units (GRUs), for both binary and multi-class classification of mental health conditions. Our findings indicate that ML and DL models achieve comparable classification performance on medium-sized datasets, with ML models offering greater interpretability through variable importance scores, while DL models are more robust to complex linguistic patterns. Additionally, ML models require explicit feature engineering, whereas DL models learn hierarchical representations directly from text. Logistic regression provides the advantage of capturing both positive and negative associations between features and mental health conditions, whereas tree-based models prioritize decision-making power through split-based feature selection. This study offers empirical insights into the advantages and limitations of different modeling approaches and provides recommendations for selecting appropriate methods based on dataset size, interpretability needs, and computational constraints.

The secondary structure of a protein is critical for establishing a link between the protein primary and tertiary structures. For this reason, it is important to design methods for accurate protein secondary structure prediction. Most of the existing computational techniques for protein structural and functional prediction are based on machine learning with shallow frameworks. Different deep learning architectures have already been applied to tackle protein secondary structure prediction problem. In this study, deep learning based models, i.e., convolutional neural network and long short-term memory for protein secondary structure prediction were proposed. The input to proposed models is amino acid sequences which were derived from CulledPDB dataset. Hyperparameter tuning with cross validation was employed to attain best parameters for the proposed models. The proposed models enables effective processing of amino acids and attain approximately 87.05% and 87.47% Q3 accuracy of protein secondary structure prediction for convolutional neural network and long short-term memory models, respectively.

Accurate RNA secondary structure information is the cornerstone of gene function research and RNA tertiary structure prediction. However, most traditional RNA secondary structure prediction algorithms are based on the dynamic programming (DP) algorithm, according to the minimum free energy theory, with both hard and soft constraints. The accuracy is particularly dependent on the accuracy of soft constraints (from experimental data like chemical and enzyme detection). With the elongation of the RNA sequence, the time complexity of DP-based algorithms will increase geometrically, as a result, they are not good at coping with relatively long sequences. Furthermore, due to the complexity of the pseudoknots structure, the secondary structure prediction method, based on traditional algorithms, has great defects which cannot predict the secondary structure with pseudoknots well. Therefore, few algorithms have been available for pseudoknots prediction in the past. The ATTfold algorithm proposed in this article is a deep learning algorithm based on an attention mechanism. It analyzes the global information of the RNA sequence via the characteristics of the attention mechanism, focuses on the correlation between paired bases, and solves the problem of long sequence prediction. Moreover, this algorithm also extracts the effective multi-dimensional features from a great number of RNA sequences and structure information, by combining the exclusive hard constraints of RNA secondary structure. Hence, it accurately determines the pairing position of each base, and obtains the real and effective RNA secondary structure, including pseudoknots. Finally, after training the ATTfold algorithm model through tens of thousands of RNA sequences and their real secondary structures, this algorithm was compared with four classic RNA secondary structure prediction algorithms. The results show that our algorithm significantly outperforms others and more accurately showed the secondary structure of RNA. As the data in RNA sequence databases increase, our deep learning-based algorithm will have superior performance. In the future, this kind of algorithm will be more indispensable.

Circular dichroism (CD) is a spectroscopic technique commonly used to investigate the structure of proteins. Major secondary structure types, alpha-helices and beta-strands, produce distinctive CD spectra. Thus, by comparing the CD spectrum of a protein of interest to a reference set consisting of CD spectra of proteins of known structure, predictive methods can estimate the secondary structure of the protein. Currently available methods, including K2D2, use such experimental CD reference sets, which are very small in size when compared to the number of tertiary structures available in the Protein Data Bank (PDB). Conversely, given a PDB structure, it is possible to predict a theoretical CD spectrum from it. The methodological framework for this calculation was established long ago but only recently a convenient implementation called DichroCalc has been developed. In this study, we set to determine whether theoretically derived spectra could be used as reference set for accurate CD based predictions of secondary structure. We used DichroCalc to calculate the theoretical CD spectra of a nonredundant set of structures representing most proteins in the PDB, and applied a straightforward approach for predicting protein secondary structure content using these theoretical CD spectra as reference set. We show that this method improves the predictions, particularly for the wavelength interval between 200 and 240 nm and for beta-strand content. We have implemented this method, called K2D3, in a publicly accessible web server at http://www. ogic.ca/projects/k2d3.