Lesion detection in women breast's dynamic contrast-enhanced magnetic resonance imaging using deep learning.

Breast cancer is one of the most common cancers in women and the second foremost cause of cancer death in women after lung cancer. Recent technological advances in breast cancer treatment offer hope to millions of women in the world. Segmentation of the breast's Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) is one of the necessary tasks in the diagnosis and detection of breast cancer. Currently, a popular deep learning model, U-Net is extensively used in biomedical image segmentation. This article aims to advance the state of the art and conduct a more in-depth analysis with a focus on the use of various U-Net models in lesion detection in women's breast DCE-MRI. In this article, we perform an empirical study of the effectiveness and efficiency of U-Net and its derived deep learning models including ResUNet, Dense UNet, DUNet, Attention U-Net, UNet++, MultiResUNet, RAUNet, Inception U-Net and U-Net GAN for lesion detection in breast DCE-MRI. All the models are applied to the benchmarked 100 Sagittal T2-Weighted fat-suppressed DCE-MRI slices of 20 patients and their performance is compared. Also, a comparative study has been conducted with V-Net, W-Net, and DeepLabV3+. Non-parametric statistical test Wilcoxon Signed Rank Test is used to analyze the significance of the quantitative results. Furthermore, Multi-Criteria Decision Analysis (MCDA) is used to evaluate overall performance focused on accuracy, precision, sensitivity, F[Formula: see text]-score, specificity, Geometric-Mean, DSC, and false-positive rate. The RAUNet segmentation model achieved a high accuracy of 99.76%, sensitivity of 85.04%, precision of 90.21%, and Dice Similarity Coefficient (DSC) of 85.04% whereas ResNet achieved 99.62% accuracy, 62.26% sensitivity, 99.56% precision, and 72.86% DSC. ResUNet is found to be the most effective model based on MCDA. On the other hand, U-Net GAN takes the least computational time to perform the segmentation task. Both quantitative and qualitative results demonstrate that the ResNet model performs better than other models in segmenting the images and lesion detection, though computational time in achieving the objectives varies.

Dense Dilated Multi-Scale Supervised Attention-Guided Network for histopathology image segmentation.

Over the last couple of decades, the introduction and proliferation of whole-slide scanners led to increasing interest in the research of digital pathology. Although manual analysis of histopathological images is still the gold standard, the process is often tedious and time consuming. Furthermore, manual analysis also suffers from intra- and interobserver variability. Separating structures or grading morphological changes can be difficult due to architectural variability of these images. Deep learning techniques have shown great potential in histopathology image segmentation that drastically reduces the time needed for downstream tasks of analysis and providing accurate diagnosis. However, few algorithms have clinical implementations. In this paper, we propose a new deep learning model Dense Dilated Multiscale Supervised Attention-Guided (D2MSA) Network for histopathology image segmentation that makes use of deep supervision coupled with a hierarchical system of novel attention mechanisms. The proposed model surpasses state-of-the-art performance while using similar computational resources. The performance of the model has been evaluated for the tasks of gland segmentation and nuclei instance segmentation, both of which are clinically relevant tasks to assess the state and progress of malignancy. Here, we have used histopathology image datasets for three different types of cancer. We have also performed extensive ablation tests and hyperparameter tuning to ensure the validity and reproducibility of the model performance. The proposed model is available at www.github.com/shirshabose/D2MSA-Net.

3PNMF-MKL: A non-negative matrix factorization-based multiple kernel learning method for multi-modal data integration and its application to gene signature detection.

In this current era, biomedical big data handling is a challenging task. Interestingly, the integration of multi-modal data, followed by significant feature mining (gene signature detection), becomes a daunting task. Remembering this, here, we proposed a novel framework, namely, three-factor penalized, non-negative matrix factorization-based multiple kernel learning with soft margin hinge loss (3PNMF-MKL) for multi-modal data integration, followed by gene signature detection. In brief, limma, employing the empirical Bayes statistics, was initially applied to each individual molecular profile, and the statistically significant features were extracted, which was followed by the three-factor penalized non-negative matrix factorization method used for data/matrix fusion using the reduced feature sets. Multiple kernel learning models with soft margin hinge loss had been deployed to estimate average accuracy scores and the area under the curve (AUC). Gene modules had been identified by the consecutive analysis of average linkage clustering and dynamic tree cut. The best module containing the highest correlation was considered the potential gene signature. We utilized an acute myeloid leukemia cancer dataset from The Cancer Genome Atlas (TCGA) repository containing five molecular profiles. Our algorithm generated a 50-gene signature that achieved a high classification AUC score (viz., 0.827). We explored the functions of signature genes using pathway and Gene Ontology (GO) databases. Our method outperformed the state-of-the-art methods in terms of computing AUC. Furthermore, we included some comparative studies with other related methods to enhance the acceptability of our method. Finally, it can be notified that our algorithm can be applied to any multi-modal dataset for data integration, followed by gene module discovery.

In silico strategies to identify protein-protein interaction modulator in cell-to-cell transmission of SARS CoV2.

RNA sequence data from SARS CoV2 patients helps to construct a gene network related to this disease. A detailed analysis of the human host response to SARS CoV2 with expression profiling by high-throughput sequencing has been accomplished with primary human lung epithelial cell lines. Using this data, the clustered gene annotation and gene network construction are performed with the help of the String database. Among the four clusters identified, only 1 with 44 genes could be annotated. Interestingly, this corresponded to basal cells with p = 1.37e - 05, which is relevant for respiratory tract infection. Functional enrichment analysis of genes present in the gene network has been completed using the String database and the Network Analyst tool. Among three types of cell-cell communication, only the anchoring junction between the basal cell membrane and the basal lamina in the host cell is involved in the virus transmission. In this junction point, a hemidesmosome structure plays a vital role in virus spread from one cell to basal lamina in the respiratory tract. In this protein complex structure, different integrin protein molecules of the host cell are used to promote the spread of virus infection into the extracellular matrix. So, small molecular blockers of different anchoring junction proteins, such as integrin alpha 3, integrin beta 1, can provide efficient protection against this deadly viral disease. ORF8 from SARS CoV2 virus can interact with both integrin proteins of human host. By using molecular docking technique, a ternary complex of these three proteins is modelled. Several oligopeptides are predicted as modulators for this ternary complex. In silico analysis of these modulators is very important to develop novel therapeutics for the treatment of SARS CoV2.

Time-Series Prediction for the Epidemic Trends of COVID-19 Using Conditional Generative Adversarial Networks Regression on Country-Wise Case Studies.

Probabilistic Regression is a statistical technique and a crucial problem in the machine learning domain which employs a set of machine learning methods to forecast a continuous target variable based on the value of one or multiple predictor variables. COVID-19 is a virulent virus that has brought the whole world to a standstill. The potential of the virus to cause inter human transmission makes the world a dangerous place. This article predicts the upcoming circumstances of the Corona virus to subside its action. We have performed Conditional GAN regression to anticipate the subsequent COVID-19 cases of five countries. The GAN variant CGAN is used to design the model and predict the COVID-19 cases for 3 months ahead with least error for the dataset provided. Each country is examined individually, due to their variation in population size, tradition, medical management and preventive measures. The analysis is based on confirmed data, as provided by the World Health Organization. This paper investigates how conditional Generative Adversarial Networks (GANs) can be used to accurately exhibit intricate conditional distributions. GANs have got spectacular achievement in producing convoluted high-dimensional data, but work done on their use for regression problems is minimal. This paper exhibits how conditional GANs can be employed in probabilistic regression. It is shown that conditional GANs can be used to evaluate a wide range of various distributions and be competitive with existing probabilistic regression models.

Passenger Surveillance Using Deep Learning in Post-COVID-19 Intelligent Transportation System.

Intelligent Transport System should be renovated in many aspects in post-pandemic situation like COVID-19. The passenger-count inside a car will be restricted based on the vehicle capacity and the COVID-19 hot-spot zone. Traffic rules will be impacted to align with a similar contagious outbreak. The on-road 'Yellow-Vulture' cameras need to incorporate such surveillance rules to monitor related anomalies for preventing contamination. To maintain safe-distance, an automatic surveillance system will be preferred by the Government very soon. Moreover, facial mask usage during the journey has become an essential habit to stop the spread of the infection. In this article, we have proposed a deep-Learning based framework that employs an augmented image data set to provide proper surveillance in the transport system to maintain the health protocols. Fast and accurate detection of the number of passengers inside a car and their face masks from the traffic inspection camera feed has been demonstrated. We have exploited the advantages of the popular Transfer Learning approach with novel variations of images while performing the training. To the best of our knowledge, this is the first attempt to watch over in-vehicle social-distancing in post-pandemic circumstances through deep-Learning based image analysis. The superiority of the proposed framework has been established over several state-of-the-art techniques using different numerical metrics and visual comparisons along with a support of statistical hypothesis test. Our technique has achieved 98.5 % testing accuracy in various adverse conditions. Zero-shot evaluation has been explored for the Real-Time-Medical-Mask-Detection data set Wang et al. (Real-Time-Medical-Mask-Detection, 2020a https://github.com/TheSSJ2612/Real-Time-Medical-Mask-Detection/, Accessed 14 Nov 2020), where we have attained 96.4 % accuracy that manifests the generalization of the network.

Epileptic-seizure onset detection using PARAFAC model with cross-wavelet transformation on multi-channel EEG.

Finding components from multi-channel EEG signal for localizing and detection of onset of seizure, is a new approach in biomedical signal analysis. Tensor-based approaches are utilized to fit the components into multi-dimensional arrays in recent works. We initially decompose EEG signals into Beta band using discrete wavelet transform (DWT). We compare patient templates with normal template for cross-wavelet analysis to obtain Wavelet cross spectrum (WCS) and Wavelet cross coherence coefficients. Next we apply parallel factorization (PARAFAC) modeling, a three-way tensor-based representation in channel, frequency and time-points dimensions on features. Finally, we utilize the ensemble classifier for detecting seizure-free, onset and seizure classes. The clinical dataset for this work comprises of 5 normal subjects and 6 epileptiform patients. The classification performances of WCS features on PARAFAC model for Seizure detection using Ensemble Bagged-Trees classifier obtains 82.21% accuracy, while for Wavelet Coherence features, it provides higher 84.76% accuracy. The results have been compared with well-known Fine Gaussian SVM, Weighted KNN and Ensemble Subspace KNN classifiers. The aim is to analyze data over three dimensions namely, time, frequency and space (channels). This EEG based analysis is significant and effective as an automatic method for detection of seizure before its actual manifestation.

A network biology approach to identify crucial host targets for COVID-19.

The ongoing global pandemic of COVID-19, caused by SARS-CoV-2 has killed more than 5.9 million individuals out of ∼43 million confirmed infections. At present, several parts of the world are encountering the 3rd wave. Mass vaccination has been started in several countries but they are less likely to be broadly available for the current pandemic, repurposing of the existing drugs has drawn highest attention for an immediate solution. A recent publication has mapped the physical interactions of SARS-CoV-2 and human proteins by affinity-purification mass spectrometry (AP-MS) and identified 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Here, we taken a network biology approach and constructed a human protein-protein interaction network (PPIN) with the above SARS-CoV-2 targeted proteins. We utilized a combination of essential network centrality measures and functional properties of the human proteins to identify the critical human targets of SARS-CoV-2. Four human proteins, namely PRKACA, RHOA, CDK5RAP2, and CEP250 have emerged as the best therapeutic targets, of which PRKACA and CEP250 were also found by another group as potential candidates for drug targets in COVID-19. We further found candidate drugs/compounds, such as guanosine triphosphate, remdesivir, adenosine monophosphate, MgATP, and H-89 dihydrochloride that bind the target human proteins. The urgency to prevent the spread of infection and the death of diseased individuals has prompted the search for agents from the pool of approved drugs to repurpose them for COVID-19. Our results indicate that host targeting therapy with the repurposed drugs may be a useful strategy for the treatment of SARS-CoV-2 infection.

Dense Dilated Deep Multiscale Supervised U-Network for biomedical image segmentation.

Biomedical image segmentation is essential for computerized medical image analysis. Deep learning algorithms allow us to design state-of-the-art models for solving segmentation problems. The U-Net and its variants have provided positive results across various datasets. However, the existing networks have the same receptive field at each level and the models are supervised only at the shallow level. Considering these two ideas, we have proposed the D3MSU-Net where the field of view in each level is varied depending upon the depth of the resolution layer and the model is supervised at each resolution level. We have evaluated our network in eight benchmark datasets such as Electron Microscopy, Lung segmentation, Montgomery Chest X-ray, Covid-Radiopaedia, Wound, Medetec, Brain MRI, and Covid-19 lung CT dataset. Additionally, we have provided the performance for various ablations. The experimental results show the superiority of the proposed network. The proposed D3MSU-Net and ablation models are available at www.github.com/shirshabose/D3MSUNET.

Study of transcription factor druggabilty for prostate cancer using structure information, gene regulatory networks and protein moonlighting.

Prostate cancer is the second leading cause of cancer-related death in men. Metastasis shows poor survival even though the recovery rate is high. In spite of numerous studies regarding prostate carcinoma, multiple questions are still unanswered. In this regards, gene regulatory network can uncover the mechanisms behind cancer progression, and metastasis. Under a feed forward loop, transcription factors (TFs) can be a good druggable candidate. We have proposed a computational model to study the uncertainty of TFs and suggest the appropriate cellular conditions for drug targeting. We have selected feed-forward loops depending on the shared list of the functional annotations among TFs, genes and miRNAs. From the potential feed forward loop cores, six TFs were identified as druggable targets, which include AR, CEBPB, CREB1, ETS1, NFKB1 and RELA. However, TFs are known for their Protein Moonlighting properties, which provide unrelated multi-functionalities within the same or different subcellular localizations. Following that, we have identified such functions that are suitable for drug targeting. On the other hand, we have tried to identify membraneless organelles for providing more specificity to the proposed time and space theory. The study has provided certain possibilities on TF-based therapeutics. The controlled dynamic nature of the TF may have enhanced the chances where TFs can be considered as one of the prime drug targets. Finally, the combination of membranless phase separation and protein moonlighting has provided possible druggable period within the biological clock.

Strategies for COVID-19 Epidemiological Surveillance in India: Overall Policies Till June 2021.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has gripped the entire world, almost paralysing the human race in its entirety. The virus rapidly transmits via human-to-human medium resulting in a massive increase of patients with COVID-19. In order to curb the spread of the disease, an immediate action of complete lockdown was implemented across the globe. India with a population of over 1.3 billion was not an exception and took the challenge to execute phase-wise lockdown, unlock and partial lockdown activities. In this study, we intend to summarise these different phases that the Government of India (GoI) imposed to fight against SARS-CoV-2 so that it can act as a reference guideline to help controlling future waves of COVID-19 and similar pandemic situations in India.

Studying the effect of alpha-synuclein and Parkinson's disease linked mutants on inter pathway connectivities.

Parkinson's disease is a common neurodegenerative disease. The differential expression of alpha-synuclein within Lewy Bodies leads to this disease. Some missense mutations of alpha-synuclein may resultant in functional aberrations. In this study, our objective is to verify the functional adaptation due to early and late-onset mutation which can trigger or control the rate of alpha-synuclein aggregation. In this regard, we have proposed a computational model to study the difference and similarities among the Wild type alpha-synuclein and mutants i.e., A30P, A53T, G51D, E46K, and H50Q. Evolutionary sequence space analysis is also performed in this experiment. Subsequently, a comparative study has been performed between structural information and sequence space outcomes. The study shows the structural variability among the selected subtypes. This information assists inter pathway modeling due to mutational aberrations. Based on the structural variability, we have identified the protein-protein interaction partners for each protein that helps to increase the robustness of the inter-pathway connectivity. Finally, few pathways have been identified from 12 semantic networks based on their association with mitochondrial dysfunction and dopaminergic pathways.

Understanding structural malleability of the SARS-CoV-2 proteins and relation to the comorbidities.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the coronavirus disease (COVID-19), is a part of the $\beta $-Coronaviridae family. The virus contains five major protein classes viz., four structural proteins [nucleocapsid (N), membrane (M), envelop (E) and spike glycoprotein (S)] and replicase polyproteins (R), synthesized as two polyproteins (ORF1a and ORF1ab). Due to the severity of the pandemic, most of the SARS-CoV-2-related research are focused on finding therapeutic solutions. However, studies on the sequences and structure space throughout the evolutionary time frame of viral proteins are limited. Besides, the structural malleability of viral proteins can be directly or indirectly associated with the dysfunctionality of the host cell proteins. This dysfunctionality may lead to comorbidities during the infection and may continue at the post-infection stage. In this regard, we conduct the evolutionary sequence-structure analysis of the viral proteins to evaluate their malleability. Subsequently, intrinsic disorder propensities of these viral proteins have been studied to confirm that the short intrinsically disordered regions play an important role in enhancing the likelihood of the host proteins interacting with the viral proteins. These interactions may result in molecular dysfunctionality, finally leading to different diseases. Based on the host cell proteins, the diseases are divided in two distinct classes: (i) proteins, directly associated with the set of diseases while showing similar activities, and (ii) cytokine storm-mediated pro-inflammation (e.g. acute respiratory distress syndrome, malignancies) and neuroinflammation (e.g. neurodegenerative and neuropsychiatric diseases). Finally, the study unveils that males and postmenopausal females can be more vulnerable to SARS-CoV-2 infection due to the androgen-mediated protein transmembrane serine protease 2.

Modeling expression ranks for noise-tolerant differential expression analysis of scRNA-seq data.

Systematic delineation of complex biological systems is an ever-challenging and resource-intensive process. Single-cell transcriptomics allows us to study cell-to-cell variability in complex tissues at an unprecedented resolution. Accurate modeling of gene expression plays a critical role in the statistical determination of tissue-specific gene expression patterns. In the past few years, considerable efforts have been made to identify appropriate parametric models for single-cell expression data. The zero-inflated version of Poisson/negative binomial and log-normal distributions have emerged as the most popular alternatives owing to their ability to accommodate high dropout rates, as commonly observed in single-cell data. Although the majority of the parametric approaches directly model expression estimates, we explore the potential of modeling expression ranks, as robust surrogates for transcript abundance. Here we examined the performance of the discrete generalized beta distribution (DGBD) on real data and devised a Wald-type test for comparing gene expression across two phenotypically divergent groups of single cells. We performed a comprehensive assessment of the proposed method to understand its advantages compared with some of the existing best-practice approaches. We concluded that besides striking a reasonable balance between Type I and Type II errors, ROSeq, the proposed differential expression test, is exceptionally robust to expression noise and scales rapidly with increasing sample size. For wider dissemination and adoption of the method, we created an R package called ROSeq and made it available on the Bioconductor platform.

Machine learning integrated ensemble of feature selection methods followed by survival analysis for predicting breast cancer subtype specific miRNA biomarkers.

Breast cancer is the second leading cancer type among females. In this regard, it is found that microRNAs play an important role by regulating the gene expressions at the post-transcriptional phase. However, identification of the most influencing miRNAs in breast cancer subtypes is a challenging task, while the recent advancement in Next Generation Sequencing techniques allows analyzing high throughput expression data of miRNAs. Thus, we have conducted this research with the help of NGS data of breast cancer in order to identify the most significant miRNA biomarkers. The selected miRNA biomarkers are highly associated with the multiple breast cancer subtypes. For this purpose, a two-phase technique, called Machine Learning Integrated Ensemble of Feature Selection Methods, followed by survival analysis, is proposed. In the first phase, we have selected the best among seven machine learning techniques based on classification accuracy using the entire set of features (in this case miRNAs). Subsequently, eight different feature selection methods are used separately in order to rank the features and validate each set of top features using the selected machine learning technique by considering a multi-class classification task of the breast cancer subtypes. In the second phase, based on the classification accuracy values, the top features from each feature selection method are considered to make an ensemble to provide further categorization of the miRNAs as 8*, 7* up to 1*. The 8* miRNAs provide the highest average classification accuracy of 86% after 10-fold cross-validation. Thereafter, 27 miRNAs are identified from the list that is confined within 8* to 4* miRNAs based on their importance in survival for breast cancer subtypes using Cox regression based survival analysis. Moreover, expression analysis, regulatory network analysis, protein-protein interaction analysis, KEGG pathway and gene ontology enrichment analysis are performed in order to validate biological significance of the proposed solution. Additionally, we have prepared a miRNA-protein-drug interaction network to identify possible drug for the selected miRNAs. Thus, our findings may be considered during a clinical trial for the treatment of breast cancer patients.

Topological Analysis for Sequence Variability: Case Study on more than 2K SARS-CoV-2 sequences of COVID-19 infected 54 countries in comparison with SARS-CoV-1 and MERS-CoV.

The pandemic due to novel coronavirus, SARS-CoV-2 is a serious global concern now. More than thousand new COVID-19 infections are getting reported daily for this virus across the globe. Thus, the medical research communities are trying to find the remedy to restrict the spreading of this virus, while the vaccine development work is still under research in parallel. In such critical situation, not only the medical research community, but also the scientists in different fields like microbiology, pharmacy, bioinformatics and data science are also sharing effort to accelerate the process of vaccine development, virus prediction, forecasting the transmissible probability and reproduction cases of virus for social awareness. With the similar context, in this article, we have studied sequence variability of the virus primarily focusing on three aspects: (a) sequence variability among SARS-CoV-1, MERS-CoV and SARS-CoV-2 in human host, which are in the same coronavirus family, (b) sequence variability of SARS-CoV-2 in human host for 54 different countries and (c) sequence variability between coronavirus family and country specific SARS-CoV-2 sequences in human host. For this purpose, as a case study, we have performed topological analysis of 2391 global genomic sequences of SARS-CoV-2 in association with SARS-CoV-1 and MERS-CoV using an integrated semi-alignment based computational technique. The results of the semi-alignment based technique are experimentally and statistically found similar to alignment based technique and computationally faster. Moreover, the outcome of this analysis can help to identify the nations with homogeneous SARS-CoV-2 sequences, so that same vaccine can be applied to their heterogeneous human population.

Structural facets of POU2F1 in light of the functional annotations and sequence-structure patterns.

POU domain class 2 homebox 1 or POU2F1 is broadly known as an important transcription factor. Due to its association with different types of malignancies, POU2F1 became one of the key factors in pancancer analysis. However, in spite of considering this protein as a potential drug target, none of the drug targeting POU2F1 has been designed as of yet due to the extreme structural flexibility of this protein. In this article, we have proposed a three-level comprehensive framework for understanding the structural conservation and co-variation of POU2F1. First, a gene regulatory network based on the normal and pathological functions of POU2F1 has been created for better understanding the strong association between POU2F1 deregulation and cancers. After that, based on the evolutionary sequence space analysis, the comparative sequence dynamics of the protein members of POU domain family has been studied mostly between non-human and human species. Subsequently, the reciprocity effect of the residual co-variation has been identified through direct coupling analysis. Along with that, the structure of POU2F1 has been analyzed depending on quality assessment and normal mode-based structure network. Comparing the sequence and structure space information, the most significant set of residues viz., 3, 9, 13, 17, 20, 21, 28, 35, and 36 have been identified as structural facet for function. This study demonstrates that the structural malleability of POU2F1 serves as one of the prime reason behind its functional multiplicity in terms of protein moonlighting. Communicated by Ramaswamy H. Sarma.

Unveiling COVID-19-associated organ-specific cell types and cell-specific pathway cascade.

The novel coronavirus or COVID-19 has first been found in Wuhan, China, and became pandemic. Angiotensin-converting enzyme 2 (ACE2) plays a key role in the host cells as a receptor of Spike-I Glycoprotein of COVID-19 which causes final infection. ACE2 is highly expressed in the bladder, ileum, kidney and liver, comparing with ACE2 expression in the lung-specific pulmonary alveolar type II cells. In this study, the single-cell RNAseq data of the five tissues from different humans are curated and cell types with high expressions of ACE2 are identified. Subsequently, the protein-protein interaction networks have been established. From the network, potential biomarkers which can form functional hubs, are selected based on k-means network clustering. It is observed that angiotensin PPAR family proteins show important roles in the functional hubs. To understand the functions of the potential markers, corresponding pathways have been researched thoroughly through the pathway semantic networks. Subsequently, the pathways have been ranked according to their influence and dependency in the network using PageRank algorithm. The outcomes show some important facts in terms of infection. Firstly, renin-angiotensin system and PPAR signaling pathway can play a vital role for enhancing the infection after its intrusion through ACE2. Next, pathway networks consist of few basic metabolic and influential pathways, e.g. insulin resistance. This information corroborate the fact that diabetic patients are more vulnerable to COVID-19 infection. Interestingly, the key regulators of the aforementioned pathways are angiontensin and PPAR family proteins. Hence, angiotensin and PPAR family proteins can be considered as possible therapeutic targets. Contact: sagnik.sen2008@gmail.com, umaulik@cse.jdvu.ac.in Supplementary information: Supplementary data are available online.

Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2.

Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role, as it is rapid and cost effective compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus affected patients, in the present alarming situation. In this paper five phytochemicals, which belong to flavonoid and anthraquinone subclass, have been selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. Their molecular binding sites on spike protein bound structure with its receptor have been analyzed. From this analysis, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19. Among them, the phytochemical hesperidin can bind with ACE2 protein and bound structure of ACE2 protein and spike protein of SARS-CoV2 noncompetitively. The binding sites of ACE2 protein for spike protein and hesperidin, are located in different parts of ACE2 protein. Ligand spike protein causes conformational change in three-dimensional structure of protein ACE2, which is confirmed by molecular docking and molecular dynamics studies. This compound modulates the binding energy of bound structure of ACE2 and spike protein. This result indicates that due to presence of hesperidin, the bound structure of ACE2 and spike protein fragment becomes unstable. As a result, this natural product can impart antiviral activity in SARS CoV2 infection. The antiviral activity of these five natural compounds are further experimentally validated with QSAR study.

A two-stage approach towards protein secondary structure classification.

Protein secondary structure (PSS) describes the local folded structures which get formed inside a polypeptide due to interactions among atoms of the backbone. Generally, globular proteins are divided into four classes, namely all-α, all-ß, α + ß, and α/ß. As nearly 90% of proteins fall into the said four classes, these are mostly considered for the purpose of computational classification of proteins. Classification of PSS is important for different biological functions that include protein fold recognition, tertiary structure prediction, prediction of DNA-binding sites, and reduction of the conformation search space among others. In this paper, we have proposed a machine learning-based model for secondary structure classification of proteins into four classes: all-α, all-ß, α + ß, and α/ß. In doing so, we have considered both sequence-based and structure-based features. At first, mutual information (MI), a filter-based feature selection method, is used to remove the redundant features, and then these selected features are used to train three different classifiers-random forest, K-nearest neighbor (KNN), and multi-layer perceptron (MLP). After that, some standard classifier combination approaches are applied to integrate the decision made by the said classifiers and it has been found that weighted product rule performs the best among all. The overall accuracies obtained using the proposed model on the four standard datasets, namely 640, 1189, 25pdb, and fc699 are 86.89%, 92.93%, 91.38%, and 94.87% respectively. The proposed model outperforms some state-of-the-art methods considered here for comparison. Significantly high classification accuracy produced by our proposed model on four datasets is attributed to the development of a comprehensive feature set (by eliminating redundant features through feature selection technique) which is then passed through an ensemble consists of three different classifiers. Assigning different weights to the outcome of different classifiers thus proved to be useful in designing the model for predicting the secondary structure of proteins based on its sequence-based and structure-based features. Graphical abstract.