Multi-Disease Detection Using a Prism-Based Surface Plasmon Resonance Sensor: A TMM and FEM Approach.

This research introduces a surface plasmon resonance (SPR)-based biosensor with multilayered structures for telecommunication wavelength in order to detect multiple diseases. The malaria and the chikungunya viruses are taken into account and the presence of these viruses are determined by examining several blood components in healthy and affected phases. Here, two distinct configurations (Al-BTO-Al-MoS2 and Cu-BTO-Cu-MoS2) are proposed and contrasted for the detection of numerous viruses. The performance characteristics of this work have been analyzed using Transfer Matrix Method (TMM) method and Finite Element Method (FEM) method under angle interrogation technique. From the TMM and FEM solutions, it is evident that the Al-BTO-Al-MoS2 structure provides the highest sensitivities of ~270 deg./RIU for malaria and ~262 deg./RIU for chikungunya viruses, with satisfactory detection accuracy of ~1.10 for malaria, ~1.64 for chikungunya, and quality factor of ~204.40 for malaria, ~208.20 for chikungunya. In addition, the Cu-BTO-Cu MoS2 structure offers the highest sensitivities of ~310 deg./RIU for malaria and ~298 deg./RIU for chikungunya, with satisfactory detection accuracy of ~0.40 for malaria, ~0.58 for chikungunya, and quality factor of ~89.85 for malaria, ~86.38 for chikungunya viruses. Therefore, the performance of the proposed sensors is analyzed using two distinct methods and gives around similar results. In a sum, this research could be utilized as a theoretical foundation and first step in the development of a real sensor.

BOO-ST and CBCEC: two novel hybrid machine learning methods aim to reduce the mortality of heart failure patients.

Heart failure (HF) is a leading cause of mortality worldwide. Machine learning (ML) approaches have shown potential as an early detection tool for improving patient outcomes. Enhancing the effectiveness and clinical applicability of the ML model necessitates training an efficient classifier with a diverse set of high-quality datasets. Hence, we proposed two novel hybrid ML methods ((a) consisting of Boosting, SMOTE, and Tomek links (BOO-ST); (b) combining the best-performing conventional classifier with ensemble classifiers (CBCEC)) to serve as an efficient early warning system for HF mortality. The BOO-ST was introduced to tackle the challenge of class imbalance, while CBCEC was responsible for training the processed and selected features derived from the Feature Importance (FI) and Information Gain (IG) feature selection techniques. We also conducted an explicit and intuitive comprehension to explore the impact of potential characteristics correlating with the fatality cases of HF. The experimental results demonstrated the proposed classifier CBCEC showcases a significant accuracy of 93.67% in terms of providing the early forecasting of HF mortality. Therefore, we can reveal that our proposed aspects (BOO-ST and CBCEC) can be able to play a crucial role in preventing the death rate of HF and reducing stress in the healthcare sector.

Identification of genetic biomarkers, drug targets and agents for respiratory diseases utilising integrated bioinformatics approaches.

Respiratory diseases (RD) are significant public health burdens and malignant diseases worldwide. However, the RD-related biological information and interconnection still need to be better understood. Thus, this study aims to detect common differential genes and potential hub genes (HubGs), emphasizing their actions, signaling pathways, regulatory biomarkers for diagnosing RD and candidate drugs for treating RD. In this paper we used integrated bioinformatics approaches (such as, gene ontology (GO) and KEGG pathway enrichment analysis, molecular docking, molecular dynamic simulation and network-based molecular interaction analysis). We discovered 73 common DEGs (CDEGs) and ten HubGs (ATAD2B, PPP1CB, FOXO1, AKT3, BCR, PDE4D, ITGB1, PCBP2, CD44 and SMARCA2). Several significant functions and signaling pathways were strongly related to RD. We recognized six transcription factor (TF) proteins (FOXC1, GATA2, FOXL1, YY1, POU2F2 and HINFP) and five microRNAs (hsa-mir-218-5p, hsa-mir-335-5p, hsa-mir-16-5p, hsa-mir-106b-5p and hsa-mir-15b-5p) as the important transcription and post-transcription regulators of RD. Ten HubGs and six major TF proteins were considered drug-specific receptors. Their binding energy analysis study was carried out with the 63 drug agents detected from network analysis. Finally, the five complexes (the PDE4D-benzo[a]pyrene, SMARCA2-benzo[a]pyrene, HINFP-benzo[a]pyrene, CD44-ketotifen and ATAD2B-ponatinib) were selected for RD based on their strong binding affinity scores and stable performance as the most probable repurposable protein-drug complexes. We believe our findings will give readers, wet-lab scientists, and pharmaceuticals a thorough grasp of the biology behind RD.

An Explainable EEG-Based Human Activity Recognition Model Using Machine-Learning Approach and LIME.

Electroencephalography (EEG) is a non-invasive method employed to discern human behaviors by monitoring the neurological responses during cognitive and motor tasks. Machine learning (ML) represents a promising tool for the recognition of human activities (HAR), and eXplainable artificial intelligence (XAI) can elucidate the role of EEG features in ML-based HAR models. The primary objective of this investigation is to investigate the feasibility of an EEG-based ML model for categorizing everyday activities, such as resting, motor, and cognitive tasks, and interpreting models clinically through XAI techniques to explicate the EEG features that contribute the most to different HAR states. The study involved an examination of 75 healthy individuals with no prior diagnosis of neurological disorders. EEG recordings were obtained during the resting state, as well as two motor control states (walking and working tasks), and a cognition state (reading task). Electrodes were placed in specific regions of the brain, including the frontal, central, temporal, and occipital lobes (Fz, C1, C2, T7, T8, Oz). Several ML models were trained using EEG data for activity recognition and LIME (Local Interpretable Model-Agnostic Explanations) was employed for interpreting clinically the most influential EEG spectral features in HAR models. The classification results of the HAR models, particularly the Random Forest and Gradient Boosting models, demonstrated outstanding performances in distinguishing the analyzed human activities. The ML models exhibited alignment with EEG spectral bands in the recognition of human activity, a finding supported by the XAI explanations. To sum up, incorporating eXplainable Artificial Intelligence (XAI) into Human Activity Recognition (HAR) studies may improve activity monitoring for patient recovery, motor imagery, the healthcare metaverse, and clinical virtual reality settings.

WheatSpikeNet: an improved wheat spike segmentation model for accurate estimation from field imaging.

Phenotyping is used in plant breeding to identify genotypes with desirable characteristics, such as drought tolerance, disease resistance, and high-yield potentials. It may also be used to evaluate the effect of environmental circumstances, such as drought, heat, and salt, on plant growth and development. Wheat spike density measure is one of the most important agronomic factors relating to wheat phenotyping. Nonetheless, due to the diversity of wheat field environments, fast and accurate identification for counting wheat spikes remains one of the challenges. This study proposes a meticulously curated and annotated dataset, named as SPIKE-segm, taken from the publicly accessible SPIKE dataset, and an optimal instance segmentation approach named as WheatSpikeNet for segmenting and counting wheat spikes from field imagery. The proposed method is based on the well-known Cascade Mask RCNN architecture with model enhancements and hyperparameter tuning to provide state-of-the-art detection and segmentation performance. A comprehensive ablation analysis incorporating many architectural components of the model was performed to determine the most efficient version. In addition, the model's hyperparameters were fine-tuned by conducting several empirical tests. ResNet50 with Deformable Convolution Network (DCN) as the backbone architecture for feature extraction, Generic RoI Extractor (GRoIE) for RoI pooling, and Side Aware Boundary Localization (SABL) for wheat spike localization comprises the final instance segmentation model. With bbox and mask mean average precision (mAP) scores of 0.9303 and 0.9416, respectively, on the test set, the proposed model achieved superior performance on the challenging SPIKE datasets. Furthermore, in comparison with other existing state-of-the-art methods, the proposed model achieved up to a 0.41% improvement of mAP in spike detection and a significant improvement of 3.46% of mAP in the segmentation tasks that will lead us to an appropriate yield estimation from wheat plants.

Systems biology approach discovers comorbidity interaction of Parkinson's disease with psychiatric disorders utilizing brain transcriptome.

Several studies found that most patients with Parkinson's disorder (PD) appear to have psychiatric symptoms such as depression, anxiety, hallucination, delusion, and cognitive dysfunction. Therefore, recognizing these psychiatrically symptoms of PD patients is crucial for both symptomatic therapy and better knowledge of the pathophysiology of PD. In order to address this issue, we created a bioinformatics framework to determine the effects of PD mRNA expression on understanding its relationship with psychiatric symptoms in PD patients. We have discovered a significant overlap between the sets of differentially expressed genes from PD exposed tissue and psychiatric disordered tissues using RNA-seq datasets. We have chosen Bipolar disorder and Schizophrenia as psychiatric disorders in our study. A number of significant correlations between PD and the occurrence of psychiatric diseases were also found by gene set enrichment analysis, investigations of the protein-protein interaction network, gene regulatory network, and protein-chemical agent interaction network. We anticipate that the results of this pathogenetic study will provide crucial information for understanding the intricate relationship between PD and psychiatric diseases.

FP-CNN: Fuzzy pooling-based convolutional neural network for lung ultrasound image classification with explainable AI.

The COVID-19 pandemic wreaks havoc on healthcare systems all across the world. In pandemic scenarios like COVID-19, the applicability of diagnostic modalities is crucial in medical diagnosis, where non-invasive ultrasound imaging has the potential to be a useful biomarker. This research develops a computer-assisted intelligent methodology for ultrasound lung image classification by utilizing a fuzzy pooling-based convolutional neural network FP-CNN with underlying evidence of particular decisions. The fuzzy-pooling method finds better representative features for ultrasound image classification. The FPCNN model categorizes ultrasound images into one of three classes: covid, disease-free (normal), and pneumonia. Explanations of diagnostic decisions are crucial to ensure the fairness of an intelligent system. This research has used Shapley Additive Explanation (SHAP) to explain the prediction of the FP-CNN models. The prediction of the black-box model is illustrated using the SHAP explanation of the intermediate layers of the black-box model. To determine the most effective model, we have tested different state-of-the-art convolutional neural network architectures with various training strategies, including fine-tuned models, single-layer fuzzy pooling models, and fuzzy pooling at all pooling layers. Among different architectures, the Xception model with all pooling layers having fuzzy pooling achieves the best classification results of 97.2% accuracy. We hope our proposed method will be helpful for the clinical diagnosis of covid-19 from lung ultrasound (LUS) images.

Particle Swarm Optimized Fuzzy CNN With Quantitative Feature Fusion for Ultrasound Image Quality Identification.

Inherently ultrasound images are susceptible to noise which leads to several image quality issues. Hence, rating of an image's quality is crucial since diagnosing diseases requires accurate and high-quality ultrasound images. This research presents an intelligent architecture to rate the quality of ultrasound images. The formulated image quality recognition approach fuses feature from a Fuzzy convolutional neural network (fuzzy CNN) and a handcrafted feature extraction method. We implement the fuzzy layer in between the last max pooling and the fully connected layer of the multiple state-of-the-art CNN models to handle the uncertainty of information. Moreover, the fuzzy CNN uses Particle swarm optimization (PSO) as an optimizer. In addition, a novel Quantitative feature extraction machine (QFEM) extracts hand-crafted features from ultrasound images. Next, the proposed method uses different classifiers to predict the image quality. The classifiers categories ultrasound images into four types (normal, noisy, blurry, and distorted) instead of binary classification into good or poor-quality images. The results of the proposed method exhibit a significant performance in accuracy (99.62%), precision (99.62%), recall (99.61%), and f1-score (99.61%). This method will assist a physician in automatically rating informative ultrasound images with steadfast operation in real-time medical diagnosis.

Inference for a Kavya-Manoharan Inverse Length Biased Exponential Distribution under Progressive-Stress Model Based on Progressive Type-II Censoring.

In this article, a new one parameter survival model is proposed using the Kavya-Manoharan (KM) transformation family and the inverse length biased exponential (ILBE) distribution. Statistical properties are obtained: quantiles, moments, incomplete moments and moment generating function. Different types of entropies such as Rényi entropy, Tsallis entropy, Havrda and Charvat entropy and Arimoto entropy are computed. Different measures of extropy such as extropy, cumulative residual extropy and the negative cumulative residual extropy are computed. When the lifetime of the item under use is assumed to follow the Kavya-Manoharan inverse length biased exponential (KMILBE) distribution, the progressive-stress accelerated life tests are considered. Some estimating approaches, such as the maximum likelihood, maximum product of spacing, least squares, and weighted least square estimations, are taken into account while using progressive type-II censoring. Furthermore, interval estimation is accomplished by determining the parameters' approximate confidence intervals. The performance of the estimation approaches is investigated using Monte Carlo simulation. The relevance and flexibility of the model are demonstrated using two real datasets. The distribution is very flexible, and it outperforms many known distributions such as the inverse length biased, the inverse Lindley model, the Lindley, the inverse exponential, the sine inverse exponential and the sine inverse Rayleigh model.

Statistical inference for a constant-stress partially accelerated life tests based on progressively hybrid censored samples from inverted Kumaraswamy distribution.

In this article, we investigate the problem of point and interval estimations under constant-stress partially accelerated life tests. The lifetime of items under use condition is assumed to follow the two-parameter inverted Kumaraswamy distribution. Based on Type-I progressively hybrid censored samples, the maximum likelihood and Bayesian methods are applied to estimate the model parameters as well as the acceleration factor. Under linear exponential, general entropy and squared error loss functions, Bayesian method outcomes are obtained. In addition, interval estimation is achieved by finding approximately confidence intervals for the parameters, as well as credible intervals. To investigate the accuracy of the obtained estimates and to compare the performance of confidence intervals, a Monte Carlo simulation is developed. Finally, a set of real data is analyzed to demonstrate the estimation procedures.

Early-Stage Detection of Ovarian Cancer Based on Clinical Data Using Machine Learning Approaches.

One of the common types of cancer for women is ovarian cancer. Still, at present, there are no drug therapies that can properly cure this deadly disease. However, early-stage detection could boost the life expectancy of the patients. The main aim of this work is to apply machine learning models along with statistical methods to the clinical data obtained from 349 patient individuals to conduct predictive analytics for early diagnosis. In statistical analysis, Student's t-test as well as log fold changes of two groups are used to find the significant blood biomarkers. Furthermore, a set of machine learning models including Random Forest (RF), Support Vector Machine (SVM), Decision Tree (DT), Extreme Gradient Boosting Machine (XGBoost), Logistic Regression (LR), Gradient Boosting Machine (GBM) and Light Gradient Boosting Machine (LGBM) are used to build classification models to stratify benign-vs.-malignant ovarian cancer patients. Both of the analysis techniques recognized that the serumsamples carbohydrate antigen 125, carbohydrate antigen 19-9, carcinoembryonic antigen and human epididymis protein 4 are the top-most significant biomarkers as well as neutrophil ratio, thrombocytocrit, hematocrit blood samples, alanine aminotransferase, calcium, indirect bilirubin, uric acid, natriumas as general chemistry tests. Moreover, the results from predictive analysis suggest that the machine learning models can classify malignant patients from benign patients with accuracy as good as 91%. Since generally, early-stage detection is not available, machine learning detection could play a significant role in cancer diagnosis.

Deep CNN-LSTM With Self-Attention Model for Human Activity Recognition Using Wearable Sensor.

Human Activity Recognition (HAR) systems are devised for continuously observing human behavior - primarily in the fields of environmental compatibility, sports injury detection, senior care, rehabilitation, entertainment, and the surveillance in intelligent home settings. Inertial sensors, e.g., accelerometers, linear acceleration, and gyroscopes are frequently employed for this purpose, which are now compacted into smart devices, e.g., smartphones. Since the use of smartphones is so widespread now-a-days, activity data acquisition for the HAR systems is a pressing need. In this article, we have conducted the smartphone sensor-based raw data collection, namely H-Activity, using an Android-OS-based application for accelerometer, gyroscope, and linear acceleration. Furthermore, a hybrid deep learning model is proposed, coupling convolutional neural network and long-short term memory network (CNN-LSTM), empowered by the self-attention algorithm to enhance the predictive capabilities of the system. In addition to our collected dataset (H-Activity), the model has been evaluated with some benchmark datasets, e.g., MHEALTH, and UCI-HAR to demonstrate the comparative performance of our model. When compared to other models, the proposed model has an accuracy of 99.93% using our collected H-Activity data, and 98.76% and 93.11% using data from MHEALTH and UCI-HAR databases respectively, indicating its efficacy in recognizing human activity recognition. We hope that our developed model could be applicable in the clinical settings and collected data could be useful for further research.

Adverse Effects of COVID-19 Vaccination: Machine Learning and Statistical Approach to Identify and Classify Incidences of Morbidity and Postvaccination Reactogenicity.

Good vaccine safety and reliability are essential for successfully countering infectious disease spread. A small but significant number of adverse reactions to COVID-19 vaccines have been reported. Here, we aim to identify possible common factors in such adverse reactions to enable strategies that reduce the incidence of such reactions by using patient data to classify and characterise those at risk. We examined patient medical histories and data documenting postvaccination effects and outcomes. The data analyses were conducted using a range of statistical approaches followed by a series of machine learning classification algorithms. In most cases, a group of similar features was significantly associated with poor patient reactions. These included patient prior illnesses, admission to hospitals and SARS-CoV-2 reinfection. The analyses indicated that patient age, gender, taking other medications, type-2 diabetes, hypertension, allergic history and heart disease are the most significant pre-existing factors associated with the risk of poor outcome. In addition, long duration of hospital treatments, dyspnoea, various kinds of pain, headache, cough, asthenia, and physical disability were the most significant clinical predictors. The machine learning classifiers that are trained with medical history were also able to predict patients with complication-free vaccination and have an accuracy score above 90%. Our study identifies profiles of individuals that may need extra monitoring and care (e.g., vaccination at a location with access to comprehensive clinical support) to reduce negative outcomes through classification approaches.

Diagnosis of hearing deficiency using EEG based AEP signals: CWT and improved-VGG16 pipeline.

Hearing deficiency is the world's most common sensation of impairment and impedes human communication and learning. Early and precise hearing diagnosis using electroencephalogram (EEG) is referred to as the optimum strategy to deal with this issue. Among a wide range of EEG control signals, the most relevant modality for hearing loss diagnosis is auditory evoked potential (AEP) which is produced in the brain's cortex area through an auditory stimulus. This study aims to develop a robust intelligent auditory sensation system utilizing a pre-train deep learning framework by analyzing and evaluating the functional reliability of the hearing based on the AEP response. First, the raw AEP data is transformed into time-frequency images through the wavelet transformation. Then, lower-level functionality is eliminated using a pre-trained network. Here, an improved-VGG16 architecture has been designed based on removing some convolutional layers and adding new layers in the fully connected block. Subsequently, the higher levels of the neural network architecture are fine-tuned using the labelled time-frequency images. Finally, the proposed method's performance has been validated by a reputed publicly available AEP dataset, recorded from sixteen subjects when they have heard specific auditory stimuli in the left or right ear. The proposed method outperforms the state-of-art studies by improving the classification accuracy to 96.87% (from 57.375%), which indicates that the proposed improved-VGG16 architecture can significantly deal with AEP response in early hearing loss diagnosis.

Designing a multi-epitope vaccine candidate to combat MERS-CoV by employing an immunoinformatics approach.

Currently, no approved vaccine is available against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease. The spike glycoprotein is typically considered a suitable target for MERS-CoV vaccine candidates. A computational strategy can be used to design an antigenic vaccine against a pathogen. Therefore, we used immunoinformatics and computational approaches to design a multi-epitope vaccine that targets the spike glycoprotein of MERS-CoV. After using numerous immunoinformatics tools and applying several immune filters, a poly-epitope vaccine was constructed comprising cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon-gamma (IFN-γ)-inducing epitopes. In addition, various physicochemical, allergenic, and antigenic profiles were evaluated to confirm the immunogenicity and safety of the vaccine. Molecular interactions, binding affinities, and the thermodynamic stability of the vaccine were examined through molecular docking and dynamic simulation approaches, during which we identified a stable and strong interaction with Toll-like receptors (TLRs). In silico immune simulations were performed to assess the immune-response triggering capabilities of the vaccine. This computational analysis suggested that the proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat viral infections; however, experimental evaluations remain necessary to verify the exact safety and immunogenicity profile of this vaccine.

Structural and Functional Elucidation of IF-3 Protein of Chloroflexus aurantiacus Involved in Protein Biosynthesis: An In Silico Approach.

Chloroflexus aurantiacus is a thermophilic bacterium that produces a multitude of proteins within its genome. Bioinformatics strategies can facilitate comprehending this organism through functional and structural interpretation assessments. This study is aimed at allocating the structure and function through an in silico approach required for bacterial protein biosynthesis. This in silico viewpoint provides copious properties, including the physicochemical properties, subcellular location, three-dimensional structure, protein-protein interactions, and functional elucidation of the protein (WP_012256288.1). The STRING program is utilized for the explication of protein-protein interactions. The in silico investigation documented the protein's hydrophilic nature with predominantly alpha (α) helices in its secondary structure. The tertiary-structure model of the protein has been shown to exhibit reasonably high consistency based on various quality assessment methods. The functional interpretation suggested that the protein can act as a translation initiation factor, a protein required for translation and protein biosynthesis. Protein-protein interactions also demonstrated high credence that the protein interconnected with 30S ribosomal subunit involved in protein synthesis. This study bioinformatically examined that the protein (WP_012256288.1) is affiliated in protein biosynthesis as a translation initiation factor IF-3 of C. aurantiacus.

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses.

The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection's outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.

Improved Transfer-Learning-Based Facial Recognition Framework to Detect Autistic Children at an Early Stage.

Autism spectrum disorder (ASD) is a complex neuro-developmental disorder that affects social skills, language, speech and communication. Early detection of ASD individuals, especially children, could help to devise and strategize right therapeutic plan at right time. Human faces encode important markers that can be used to identify ASD by analyzing facial features, eye contact, and so on. In this work, an improved transfer-learning-based autism face recognition framework is proposed to identify kids with ASD in the early stages more precisely. Therefore, we have collected face images of children with ASD from the Kaggle data repository, and various machine learning and deep learning classifiers and other transfer-learning-based pre-trained models were applied. We observed that our improved MobileNet-V1 model demonstrates the best accuracy of 90.67% and the lowest 9.33% value of both fall-out and miss rate compared to the other classifiers and pre-trained models. Furthermore, this classifier is used to identify different ASD groups investigating only autism image data using k-means clustering technique. Thus, the improved MobileNet-V1 model showed the highest accuracy (92.10%) for k = 2 autism sub-types. We hope this model will be useful for physicians to detect autistic children more explicitly at the early stage.

Network-based transcriptomic analysis identifies the genetic effect of COVID-19 to chronic kidney disease patients: A bioinformatics approach.

COVID-19 has emerged as global health threats. Chronic kidney disease (CKD) patients are immune-compromised and may have a high risk of infection by the SARS-CoV-2. We aimed to detect common transcriptomic signatures and pathways between COVID-19 and CKD by systems biology analysis. We analyzed transcriptomic data obtained from peripheral blood mononuclear cells (PBMC) infected with SARS-CoV-2 and PBMC of CKD patients. We identified 49 differentially expressed genes (DEGs) which were common between COVID-19 and CKD. The gene ontology and pathways analysis showed the DEGs were associated with "platelet degranulation", "regulation of wound healing", "platelet activation", "focal adhesion", "regulation of actin cytoskeleton" and "PI3K-Akt signalling pathway". The protein-protein interaction (PPI) network encoded by the common DEGs showed ten hub proteins (EPHB2, PRKAR2B, CAV1, ARHGEF12, HSP90B1, ITGA2B, BCL2L1, E2F1, TUBB1, and C3). Besides, we identified significant transcription factors and microRNAs that may regulate the common DEGs. We investigated protein-drug interaction analysis and identified potential drugs namely, aspirin, estradiol, rapamycin, and nebivolol. The identified common gene signature and pathways between COVID-19 and CKD may be therapeutic targets in COVID-19 patients with CKD comorbidity.

Bioinformatics and system biology approaches to identify the diseasome and comorbidities complexities of SARS-CoV-2 infection with the digestive tract disorders.

Coronavirus Disease 2019 (COVID-19), although most commonly demonstrates respiratory symptoms, but there is a growing set of evidence reporting its correlation with the digestive tract and faeces. Interestingly, recent studies have shown the association of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with gastrointestinal symptoms in infected patients but any sign of respiratory issues. Moreover, some studies have also shown that the presence of live SARS-CoV-2 virus in the faeces of patients with COVID-19. Therefore, the pathophysiology of digestive symptoms associated with COVID-19 has raised a critical need for comprehensive investigative efforts. To address this issue we have developed a bioinformatics pipeline involving a system biological framework to identify the effects of SARS-CoV-2 messenger RNA expression on deciphering its association with digestive symptoms in COVID-19 positive patients. Using two RNA-seq datasets derived from COVID-19 positive patients with celiac (CEL), Crohn's (CRO) and ulcerative colitis (ULC) as digestive disorders, we have found a significant overlap between the sets of differentially expressed genes from SARS-CoV-2 exposed tissue and digestive tract disordered tissues, reporting 7, 22 and 13 such overlapping genes, respectively. Moreover, gene set enrichment analysis, comprehensive analyses of protein-protein interaction network, gene regulatory network, protein-chemical agent interaction network revealed some critical association between SARS-CoV-2 infection and the presence of digestive disorders. The infectome, diseasome and comorbidity analyses also discover the influences of the identified signature genes in other risk factors of SARS-CoV-2 infection to human health. We hope the findings from this pathogenetic analysis may reveal important insights in deciphering the complex interplay between COVID-19 and digestive disorders and underpins its significance in therapeutic development strategy to combat against COVID-19 pandemic.