PRIEST: predicting viral mutations with immune escape capability of SARS-CoV-2 using temporal evolutionary information.

The dynamic evolution of the severe acute respiratory syndrome coronavirus 2 virus is primarily driven by mutations in its genetic sequence, culminating in the emergence of variants with increased capability to evade host immune responses. Accurate prediction of such mutations is fundamental in mitigating pandemic spread and developing effective control measures. This study introduces a robust and interpretable deep-learning approach called PRIEST. This innovative model leverages time-series viral sequences to foresee potential viral mutations. Our comprehensive experimental evaluations underscore PRIEST's proficiency in accurately predicting immune-evading mutations. Our work represents a substantial step in utilizing deep-learning methodologies for anticipatory viral mutation analysis and pandemic response.

DeepBend: An interpretable model of DNA bendability.

The bendability of genomic DNA impacts chromatin packaging and protein-DNA binding. However, we do not have a comprehensive understanding of the motifs influencing DNA bendability. Recent high-throughput technologies such as Loop-Seq offer an opportunity to address this gap but the lack of accurate and interpretable machine learning models still remains. Here we introduce DeepBend, a convolutional neural network model with convolutions designed to directly capture the motifs underlying DNA bendability and their periodic occurrences or relative arrangements that modulate bendability. DeepBend consistently performs on par with alternative models while giving an extra edge through mechanistic interpretations. Besides confirming the known motifs of DNA bendability, DeepBend also revealed several novel motifs and showed how the spatial patterns of motif occurrences influence bendability. DeepBend's genome-wide prediction of bendability further showed how bendability is linked to chromatin conformation and revealed the motifs controlling the bendability of topologically associated domains and their boundaries.

COVID-19Base v3: Update of the knowledgebase for drugs and biomedical entities linked to COVID-19.

COVID-19 has taken a huge toll on our lives over the last 3 years. Global initiatives put forward by all stakeholders are still in place to combat this pandemic and help us learn lessons for future ones. While the vaccine rollout was not able to curb the spread of the disease for all strains, the research community is still trying to develop effective therapeutics for COVID-19. Although Paxlovid and remdesivir have been approved by the FDA against COVID-19, they are not free of side effects. Therefore, the search for a therapeutic solution with high efficacy continues in the research community. To support this effort, in this latest version (v3) of COVID-19Base, we have summarized the biomedical entities linked to COVID-19 that have been highlighted in the scientific literature after the vaccine rollout. Eight different topic-specific dictionaries, i.e., gene, miRNA, lncRNA, PDB entries, disease, alternative medicines registered under clinical trials, drugs, and the side effects of drugs, were used to build this knowledgebase. We have introduced a BLSTM-based deep-learning model to predict the drug-disease associations that outperforms the existing model for the same purpose proposed in the earlier version of COVID-19Base. For the very first time, we have incorporated disease-gene, disease-miRNA, disease-lncRNA, and drug-PDB associations covering the largest number of biomedical entities related to COVID-19. We have provided examples of and insights into different biomedical entities covered in COVID-19Base to support the research community by incorporating all of these entities under a single platform to provide evidence-based support from the literature. COVID-19Base v3 can be accessed from: https://covidbase-v3.vercel.app/. The GitHub repository for the source code and data dictionaries is available to the community from: https://github.com/91Abdullah/covidbasev3.0.

Align-gram: Rethinking the Skip-gram Model for Protein Sequence Analysis.

The inception of next generations sequencing technologies have exponentially increased the volume of biological sequence data. Protein sequences, being quoted as the 'language of life', has been analyzed for a multitude of applications and inferences. Owing to the rapid development of deep learning, in recent years there have been a number of breakthroughs in the domain of Natural Language Processing. Since these methods are capable of performing different tasks when trained with a sufficient amount of data, off-the-shelf models are used to perform various biological applications. In this study, we investigated the applicability of the popular Skip-gram model for protein sequence analysis and made an attempt to incorporate some biological insights into it. We propose a novel k-mer embedding scheme, Align-gram, which is capable of mapping the similar k-mers close to each other in a vector space. Furthermore, we experiment with other sequence-based protein representations and observe that the embeddings derived from Align-gram aids modeling and training deep learning models better. Our experiments with a simple baseline LSTM model and a much complex CNN model of DeepGoPlus shows the potential of Align-gram in performing different types of deep learning applications for protein sequence analysis.

MAMMLE: A Framework for Phylogeny Estimation Based on Multiobjective Application-aware Multiple Sequence Alignment and Maximum Likelihood Ensemble.

Motivation: Phylogenetic trees are often inferred from a multiple sequence alignment (MSA) where the tree accuracy is heavily impacted by the nature of estimated alignment. Carefully equipping an MSA tool with multiple application-aware objectives positively impacts its capability to yield better trees. Results: We introduce Multiobjective Application-aware Multiple Sequence Alignment and Maximum Likelihood Ensemble (MAMMLE), a framework for inferring better phylogenetic trees from unaligned sequences by hybridizing two MSA tools [i.e., Multiple Sequence Comparison by Log-Expectation (MUSCLE) and Multiple Alignment using Fast Fourier Transform (MAFFT)] with multiobjective optimization strategy and leveraging multiple maximum likelihood hypotheses. In our experiments, MAMMLE exhibits 5.57% (4.77%) median improvement (deterioration) over MUSCLE on 50.34% (37.41%) of instances.

Quantifying imbalanced classification methods for leukemia detection.

Uncontrolled proliferation of B-lymphoblast cells is a common characterization of Acute Lymphoblastic Leukemia (ALL). B-lymphoblasts are found in large numbers in peripheral blood in malignant cases. Early detection of the cell in bone marrow is essential as the disease progresses rapidly if left untreated. However, automated classification of the cell is challenging, owing to its fine-grained variability with B-lymphoid precursor cells and imbalanced data points. Deep learning algorithms demonstrate potential for such fine-grained classification as well as suffer from the imbalanced class problem. In this paper, we explore different deep learning-based State-Of-The-Art (SOTA) approaches to tackle imbalanced classification problems. Our experiment includes input, GAN (Generative Adversarial Networks), and loss-based methods to mitigate the issue of imbalanced class on the challenging C-NMC and ALLIDB-2 dataset for leukemia detection. We have shown empirical evidence that loss-based methods outperform GAN-based and input-based methods in imbalanced classification scenarios.

Succinylated lysine residue prediction revisited.

Lysine succinylation is a kind of post-translational modification (PTM) that plays a crucial role in regulating the cellular processes. Aberrant succinylation may cause inflammation, cancers, metabolism diseases and nervous system diseases. The experimental methods to detect succinylation sites are time-consuming and costly. This thus calls for computational models with high efficacy, and attention has been given in the literature to develop such models, albeit with only moderate success in the context of different evaluation metrics. One crucial aspect in this context is the biochemical and physicochemical properties of amino acids, which appear to be useful as features for such computational predictors. However, some of the existing computational models did not use the biochemical and physicochemical properties of amino acids. In contrast, some others used them without considering the inter-dependency among the properties. The combinations of biochemical and physicochemical properties derived through our optimization process achieve better results than the results achieved by combining all the properties. We propose three deep learning architectures: CNN+Bi-LSTM (CBL), Bi-LSTM+CNN (BLC) and their combination (CBL_BLC). We find that CBL_BLC outperforms the other two. Ensembling of different models successfully improves the results. Notably, tuning the threshold of the ensemble classifiers further improves the results. Upon comparing our work with other existing works on two datasets, we successfully achieve better sensitivity and specificity by varying the threshold value.

A novel customer churn prediction model for the telecommunication industry using data transformation methods and feature selection.

Customer churn is one of the most critical issues faced by the telecommunication industry (TCI). Researchers and analysts leverage customer relationship management (CRM) data through the use of various machine learning models and data transformation methods to identify the customers who are likely to churn. While several studies have been conducted in the customer churn prediction (CCP) context in TCI, a review of performance of the various models stemming from these studies show a clear room for improvement. Therefore, to improve the accuracy of customer churn prediction in the telecommunication industry, we have investigated several machine learning models, as well as, data transformation methods. To optimize the prediction models, feature selection has been performed using univariate technique and the best hyperparameters have been selected using the grid search method. Subsequently, experiments have been conducted on several publicly available TCI datasets to assess the performance of our models in terms of the widely used evaluation metrics, such as AUC, precision, recall, and F-measure. Through a rigorous experimental study, we have demonstrated the benefit of applying data transformation methods as well as feature selection while training an optimized CCP model. Our proposed technique improved the prediction performance by up to 26.2% and 17% in terms of AUC and F-measure, respectively.

Country-Level Governance Indicators as Predictors of COVID-19 Morbidity, Mortality, and Vaccination Coverage: An Exploratory Global Analysis.

As the COVID-19 pandemic continues to affect all countries across the globe, this study seeks to investigate the relationship between nations' governance, COVID-19 national data, and nation-level COVID-19 vaccination coverage. National-level governance indicators (corruption index, voice and accountability, political stability, and absence of violence/terrorism), officially reported COVID-19 national data (cases, death, and tests per one million population), and COVID-19 vaccination coverage was considered for this study to predict COVID-19 morbidity and mortality. Results indicate a strong relationship between nations' governance and officially reported COVID-19 data. Countries were grouped into three clusters using only the governance data: politically stable countries, average countries or "less corrupt countries," and corrupt countries or "more corrupt countries." The clusters were then tested for significant differences in reporting various aspects of the COVID-19 data. According to multinomial regression, countries in the cluster of politically stable nations reported significantly more deaths, tests per one million, total cases per one million, and higher vaccination coverage compared with nations both in the clusters of corrupt countries and average countries. The countries in the cluster of average nations reported more tests per one million and higher vaccination coverage than countries in the cluster of corrupt nations. Countries included in the corrupt cluster reported a lower death rate and morbidity, particularly compared with the politically stable nations cluster, a trend that can be attributed to poor governance and inaccurate COVID-19 data reporting. The epidemic evaluation indices of the COVID-19 cases demonstrate that the pandemic is still evolving on a global level.

PPG2ABP: Translating Photoplethysmogram (PPG) Signals to Arterial Blood Pressure (ABP) Waveforms.

Cardiovascular diseases are one of the most severe causes of mortality, annually taking a heavy toll on lives worldwide. Continuous monitoring of blood pressure seems to be the most viable option, but this demands an invasive process, introducing several layers of complexities and reliability concerns due to non-invasive techniques not being accurate. This motivates us to develop a method to estimate the continuous arterial blood pressure (ABP) waveform through a non-invasive approach using Photoplethysmogram (PPG) signals. We explore the advantage of deep learning, as it would free us from sticking to ideally shaped PPG signals only by making handcrafted feature computation irrelevant, which is a shortcoming of the existing approaches. Thus, we present PPG2ABP, a two-stage cascaded deep learning-based method that manages to estimate the continuous ABP waveform from the input PPG signal with a mean absolute error of 4.604 mmHg, preserving the shape, magnitude, and phase in unison. However, the more astounding success of PPG2ABP turns out to be that the computed values of Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP), and Systolic Blood Pressure (SBP) from the estimated ABP waveform outperform the existing works under several metrics (mean absolute error of 3.449 ± 6.147 mmHg, 2.310 ± 4.437 mmHg, and 5.727 ± 9.162 mmHg, respectively), despite that PPG2ABP is not explicitly trained to do so. Notably, both for DBP and MAP, we achieve Grade A in the BHS (British Hypertension Society) Standard and satisfy the AAMI (Association for the Advancement of Medical Instrumentation) standard.

Quartet Based Gene Tree Imputation Using Deep Learning Improves Phylogenomic Analyses Despite Missing Data.

Species tree estimation is frequently based on phylogenomic approaches that use multiple genes from throughout the genome. However, for a combination of reasons (ranging from sampling biases to more biological causes, as in gene birth and loss), gene trees are often incomplete, meaning that not all species of interest have a common set of genes. Incomplete gene trees can potentially impact the accuracy of phylogenomic inference. We, for the first time, introduce the problem of imputing the quartet distribution induced by a set of incomplete gene trees, which involves adding the missing quartets back to the quartet distribution. We present Quartet based Gene tree Imputation using Deep Learning (QT-GILD), an automated and specially tailored unsupervised deep learning technique, accompanied by cues from natural language processing, which learns the quartet distribution in a given set of incomplete gene trees and generates a complete set of quartets accordingly. QT-GILD is a general-purpose technique needing no explicit modeling of the subject system or reasons for missing data or gene tree heterogeneity. Experimental studies on a collection of simulated and empirical datasets suggest that QT-GILD can effectively impute the quartet distribution, which results in a dramatic improvement in the species tree accuracy. Remarkably, QT-GILD not only imputes the missing quartets but can also account for gene tree estimation error. Therefore, QT-GILD advances the state-of-the-art in species tree estimation from gene trees in the face of missing data.

Multinomial Convolutions for Joint Modeling of Regulatory Motifs and Sequence Activity Readouts.

A common goal in the convolutional neural network (CNN) modeling of genomic data is to discover specific sequence motifs. Post hoc analysis methods aid in this task but are dependent on parameters whose optimal values are unclear and applying the discovered motifs to new genomic data is not straightforward. As an alternative, we propose to learn convolutions as multinomial distributions, thus streamlining interpretable motif discovery with CNN model fitting. We developed MuSeAM (Multinomial CNNs for Sequence Activity Modeling) by implementing multinomial convolutions in a CNN model. Through benchmarking, we demonstrate the efficacy of MuSeAM in accurately modeling genomic data while fitting multinomial convolutions that recapitulate known transcription factor motifs.

Linking Tweets Towards Geo-Localized Policies: COVID-19 Perspective.

COVID-19 pandemic is taking a toll on the social, economic, and psychological well-being of people. During this pandemic period, people have utilized social media platforms (e.g., Twitter) to communicate with each other and share their concerns and updates. In this study, we analyzed nearly 25M COVID-19 related tweets generated from 20 different countries and 28 states of USA over a month. We leveraged sentiment analysis and topic modeling over this collection and clustered different geolocations based on their sentiment. Our analysis identified 3 geo-clusters (country- and US state-based) based on public sentiment and discovered 15 topics that could be summarized under three main themes: government actions, medical issues, and people's mood during the home quarantine. The proposed computational pipeline has adequately captured the Twitter population's emotion and sentiment, which could be linked to government/policy makers' decisions and actions (or lack thereof). We believe that our analysis pipeline could be instrumental for the policymakers in sensing the public emotion/support with respect to the interventions/actions taken, for example, by the government instrumentality.

Phylogenetic Analyses of SARS-CoV-2 Strains Reveal Its Link to the Spread of COVID-19 Across the Globe.

This study leveraged the phylogenetic analysis of more than 10K strains of novel coronavirus (SARS-CoV-2) from 67 countries. Due to the requirement of high-end computational power for phylogenetic analysis, we leverage a fast yet highly accurate alignment-free method to develop the phylogenetic tree out of all the strains of novel coronavirus. K-Means clustering and PCA-based dimension reduction technique were used to identify a representative strain from each location. The resulting phylogenetic tree was able to highlight evolutionary relationships of SARS-CoV-2 genome and, subsequently, linked to the interpretation of facts and figures across the globe for the spread of COVID-19. Our analysis revealed that the geographical boundaries could not be explained by the phylogenetic analysis of novel coronavirus as it placed different countries from Asia, Europe and the USA in very close proximity in the tree. Instead, the commute of people from one country to another is the key to the spread of COVID-19. We believe our study will support the policymakers to contain the spread of COVID-19 globally.

Characterization of intrinsically disordered regions in proteins informed by human genetic diversity.

All proteomes contain both proteins and polypeptide segments that don't form a defined three-dimensional structure yet are biologically active-called intrinsically disordered proteins and regions (IDPs and IDRs). Most of these IDPs/IDRs lack useful functional annotation limiting our understanding of their importance for organism fitness. Here we characterized IDRs using protein sequence annotations of functional sites and regions available in the UniProt knowledgebase ("UniProt features": active site, ligand-binding pocket, regions mediating protein-protein interactions, etc.). By measuring the statistical enrichment of twenty-five UniProt features in 981 IDRs of 561 human proteins, we identified eight features that are commonly located in IDRs. We then collected the genetic variant data from the general population and patient-based databases and evaluated the prevalence of population and pathogenic variations in IDPs/IDRs. We observed that some IDRs tolerate 2 to 12-times more single amino acid-substituting missense mutations than synonymous changes in the general population. However, we also found that 37% of all germline pathogenic mutations are located in disordered regions of 96 proteins. Based on the observed-to-expected frequency of mutations, we categorized 34 IDRs in 20 proteins (DDX3X, KIT, RB1, etc.) as intolerant to mutation. Finally, using statistical analysis and a machine learning approach, we demonstrate that mutation-intolerant IDRs carry a distinct signature of functional features. Our study presents a novel approach to assign functional importance to IDRs by leveraging the wealth of available genetic data, which will aid in a deeper understating of the role of IDRs in biological processes and disease mechanisms.

PASTA with many application-aware optimization criteria for alignment based phylogeny inference.

Multiple sequence alignment (MSA) is a prerequisite for several analyses in bioinformatics, such as, phylogeny estimation, protein structure prediction, etc. PASTA (Practical Alignments using SATé and TrAnsitivity) is a state-of-the-art method for computing MSAs, well-known for its accuracy and scalability. It iteratively co-estimates both MSA and maximum likelihood (ML) phylogenetic tree. It attempts to exploit the close association between the accuracy of an MSA and the corresponding tree while finding the output through multiple iterations from both directions. Currently, PASTA uses the ML score as its optimization criterion which is a good score in phylogeny estimation but cannot be proven as a necessary and sufficient criterion to produce an accurate phylogenetic tree. Therefore, the integration of multiple application-aware objectives into PASTA, which are carefully chosen considering their better association to the tree accuracy, may potentially have a profound positive impact on its performance. This paper has employed four application-aware objectives alongside ML score to develop a multi-objective (MO) framework, namely, PMAO that leverages PASTA to generate a bunch of high-quality solutions that are considered equivalent in the context of conflicting objectives under consideration. our experimental analysis on a popular biological benchmark reveals that the tree-space generated by PMAO contains significantly better trees than stand-alone PASTA. To help the domain experts further in choosing the most appropriate tree from the PMAO output (containing a relatively large set of high-quality solutions), we have added an additional component within the PMAO framework that is capable of generating a smaller set of high-quality solutions. Finally, we have attempted to obtain a single high-quality solution without using any external evidences and have found that summarizing the few solutions detected through the above component can serve this purpose to some extent.

Revisiting segmentation of lung tumors from CT images.

Lung cancer is a leading cause of death throughout the world. Because the prompt diagnosis of tumors allows oncologists to discern their nature, type, and mode of treatment, tumor detection and segmentation from CT scan images is a crucial field of study. This paper investigates lung tumor segmentation via a two-dimensional Discrete Wavelet Transform (DWT) on the LOTUS dataset (31,247 training, and 4458 testing samples) and a Deeply Supervised MultiResUNet model. Coupling the DWT, which is used to achieve a more meticulous textural analysis while integrating information from neighboring CT slices, with the deep supervision of the model architecture results in an improved dice coefficient of 0.8472. A key characteristic of our approach is its avoidance of 3D kernels (despite being used for a 3D segmentation task), thereby making it quite lightweight.

Predicting Pulmonary Function From the Analysis of Voice: A Machine Learning Approach.

INTRODUCTION: To self-monitor asthma symptoms, existing methods (e.g. peak flow metre, smart spirometer) require special equipment and are not always used by the patients. Voice recording has the potential to generate surrogate measures of lung function and this study aims to apply machine learning approaches to predict lung function and severity of abnormal lung function from recorded voice for asthma patients. METHODS: A threshold-based mechanism was designed to separate speech and breathing from 323 recordings. Features extracted from these were combined with biological factors to predict lung function. Three predictive models were developed using Random Forest (RF), Support Vector Machine (SVM), and linear regression algorithms: (a) regression models to predict lung function, (b) multi-class classification models to predict severity of lung function abnormality, and (c) binary classification models to predict lung function abnormality. Training and test samples were separated (70%:30%, using balanced portioning), features were normalised, 10-fold cross-validation was used and model performances were evaluated on the test samples. RESULTS: The RF-based regression model performed better with the lowest root mean square error of 10·86. To predict severity of lung function impairment, the SVM-based model performed best in multi-class classification (accuracy = 73.20%), whereas the RF-based model performed best in binary classification models for predicting abnormal lung function (accuracy = 85%). CONCLUSION: Our machine learning approaches can predict lung function, from recorded voice files, better than published approaches. This technique could be used to develop future telehealth solutions including smartphone-based applications which have potential to aid decision making and self-monitoring in asthma.

A Shallow U-Net Architecture for Reliably Predicting Blood Pressure (BP) from Photoplethysmogram (PPG) and Electrocardiogram (ECG) Signals.

Cardiovascular diseases are the most common causes of death around the world. To detect and treat heart-related diseases, continuous blood pressure (BP) monitoring along with many other parameters are required. Several invasive and non-invasive methods have been developed for this purpose. Most existing methods used in hospitals for continuous monitoring of BP are invasive. On the contrary, cuff-based BP monitoring methods, which can predict systolic blood pressure (SBP) and diastolic blood pressure (DBP), cannot be used for continuous monitoring. Several studies attempted to predict BP from non-invasively collectible signals such as photoplethysmograms (PPG) and electrocardiograms (ECG), which can be used for continuous monitoring. In this study, we explored the applicability of autoencoders in predicting BP from PPG and ECG signals. The investigation was carried out on 12,000 instances of 942 patients of the MIMIC-II dataset, and it was found that a very shallow, one-dimensional autoencoder can extract the relevant features to predict the SBP and DBP with state-of-the-art performance on a very large dataset. An independent test set from a portion of the MIMIC-II dataset provided a mean absolute error (MAE) of 2.333 and 0.713 for SBP and DBP, respectively. On an external dataset of 40 subjects, the model trained on the MIMIC-II dataset provided an MAE of 2.728 and 1.166 for SBP and DBP, respectively. For both the cases, the results met British Hypertension Society (BHS) Grade A and surpassed the studies from the current literature.

Gulf Cooperation Council Clinical Trials in the Pursuit of Medications for COVID-19.

Tremendous changes have been witnessed in the post-COVID-19 world. Global efforts were initiated to reach a successful treatment for this emerging disease. These efforts have focused on developing vaccinations and/or finding therapeutic agents that can be used to combat the virus or reduce its accompanying symptoms. Gulf Cooperation Council (GCC) countries have initiated efforts on many clinical trials to address the efficacy and the safety of several therapeutic agents used for COVID-19 treatment. In this article, we provide an overview of the GCC's clinical trials and associated drugs' discovery process in the pursuit of an effective medication for COVID-19.