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Sci Data ; 9(1): 548, 2022 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071074


Computational methods and recently modern machine learning methods have played a key role in structure-based drug design. Though several benchmarking datasets are available for machine learning applications in virtual screening, accurate prediction of binding affinity for a protein-ligand complex remains a major challenge. New datasets that allow for the development of models for predicting binding affinities better than the state-of-the-art scoring functions are important. For the first time, we have developed a dataset, PLAS-5k comprised of 5000 protein-ligand complexes chosen from PDB database. The dataset consists of binding affinities along with energy components like electrostatic, van der Waals, polar and non-polar solvation energy calculated from molecular dynamics simulations using MMPBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) method. The calculated binding affinities outperformed docking scores and showed a good correlation with the available experimental values. The availability of energy components may enable optimization of desired components during machine learning-based drug design. Further, OnionNet model has been retrained on PLAS-5k dataset and is provided as a baseline for the prediction of binding affinities.

Simulação de Dinâmica Molecular , Proteínas , Animais , Humanos , Ligantes , Aprendizado de Máquina , Ligação Proteica , Proteínas/química
PLoS One ; 17(3): e0264785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35298502


The variability of clinical course and prognosis of COVID-19 highlights the necessity of patient sub-group risk stratification based on clinical data. In this study, clinical data from a cohort of Indian COVID-19 hospitalized patients is used to develop risk stratification and mortality prediction models. We analyzed a set of 70 clinical parameters including physiological and hematological for developing machine learning models to identify biomarkers. We also compared the Indian and Wuhan cohort, and analyzed the role of steroids. A bootstrap averaged ensemble of Bayesian networks was also learned to construct an explainable model for discovering actionable influences on mortality and days to outcome. We discovered blood parameters, diabetes, co-morbidity and SpO2 levels as important risk stratification features, whereas mortality prediction is dependent only on blood parameters. XGboost and logistic regression model yielded the best performance on risk stratification and mortality prediction, respectively (AUC score 0.83, AUC score 0.92). Blood coagulation parameters (ferritin, D-Dimer and INR), immune and inflammation parameters IL6, LDH and Neutrophil (%) are common features for both risk and mortality prediction. Compared with Wuhan patients, Indian patients with extreme blood parameters indicated higher survival rate. Analyses of medications suggest that a higher proportion of survivors and mild patients who were administered steroids had extreme neutrophil and lymphocyte percentages. The ensemble averaged Bayesian network structure revealed serum ferritin to be the most important predictor for mortality and Vitamin D to influence severity independent of days to outcome. The findings are important for effective triage during strains on healthcare infrastructure.

COVID-19/mortalidade , Hospitalização/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , COVID-19/epidemiologia , COVID-19/etiologia , Criança , China/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Medição de Risco/métodos , Fatores de Risco , Adulto Jovem
Front Public Health ; 9: 626697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055710


The coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is an acute respiratory disease that has been classified as a pandemic by the World Health Organization (WHO). The sudden spike in the number of infections and high mortality rates have put immense pressure on the public healthcare systems. Hence, it is crucial to identify the key factors for mortality prediction to optimize patient treatment strategy. Different routine blood test results are widely available compared to other forms of data like X-rays, CT-scans, and ultrasounds for mortality prediction. This study proposes machine learning (ML) methods based on blood tests data to predict COVID-19 mortality risk. A powerful combination of five features: neutrophils, lymphocytes, lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hs-CRP), and age helps to predict mortality with 96% accuracy. Various ML models (neural networks, logistic regression, XGBoost, random forests, SVM, and decision trees) have been trained and performance compared to determine the model that achieves consistently high accuracy across the days that span the disease. The best performing method using XGBoost feature importance and neural network classification, predicts with an accuracy of 90% as early as 16 days before the outcome. Robust testing with three cases based on days to outcome confirms the strong predictive performance and practicality of the proposed model. A detailed analysis and identification of trends was performed using these key biomarkers to provide useful insights for intuitive application. This study provide solutions that would help accelerate the decision-making process in healthcare systems for focused medical treatments in an accurate, early, and reliable manner.

COVID-19 , Sistemas de Apoio a Decisões Clínicas , Humanos , Aprendizado de Máquina , Redes Neurais de Computação , SARS-CoV-2
J Mech Behav Biomed Mater ; 118: 104460, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33773238


Owing to its inductive attributes, hydroxyapatite is an ideal reinforcement to tailor the degradation kinetics of magnesium-based temporary orthopedic implants. However, the large difference in the melting temperature of hydroxyapatite and magnesium lead to an insignificant interaction between them during the sintering process, which has been a major limitation in their consolidation. Doping of pure HA with Mg2+ and Zn2+ ions could be a viable solution by making it coherent with the Mg matrix. Further, such doping also results in a chemistry more similar to the natural apatite in human bone. In this study, Mg2+ and Zn2+ ions doped hydroxyapatite (CoHA) is synthesized and reinforced to obtain high density in Mg-based composites, fabricated through spark plasma sintering. Composite with 15 wt % CoHA offered ~113% improvement in the ultimate compressive strength. Higher relative density, due to improved consolidation, might be the reason for higher mechanical strength. Hydrogen evolution (up to 64 h) and static immersion studies (up to 28 days) revealed comparatively higher corrosion resistance for 10 wt% CoHA composites. This study gives insight into the potential of fabrication and designing of the M3Z-CoHA composites for temporary orthopedic implants.

Durapatita , Magnésio , Força Compressiva , Corrosão , Humanos , Teste de Materiais