Predicting Genetic Variation Severity Using Machine Learning to Interpret Molecular Simulations.
Ontology highlight
ABSTRACT:
SUBMITTER: McCoy MD
PROVIDER: S-EPMC7840418 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Predicting Genetic Variation Severity Using Machine Learning to Interpret Molecular Simulations.
McCoy Matthew D MD Hamre John J Klimov Dmitri K DK Jafri M Saleet MS
Biophysical journal 20201215 2
Distinct missense mutations in a specific gene have been associated with different diseases as well as differing severity of a disease. Current computational methods predict the potential pathogenicity of a missense variant but fail to differentiate between separate disease or severity phenotypes. We have developed a method to overcome this limitation by applying machine learning to features extracted from molecular dynamics simulations, creating a way to predict the effect of novel genetic vari ...[more]
Similar Datasets
Project description:The application of machine learning to predict materials' properties usually requires a large number of consistent data for training. However, experimental datasets of high quality are not always available or self-consistent. Here, as an alternative route, we combine machine learning with high-throughput molecular dynamics simulations to predict the Young's modulus of silicate glasses. We demonstrate that this combined approach offers good and reliable predictions over the entire compositional domain. By comparing the performances of select machine learning algorithms, we discuss the nature of the balance between accuracy, simplicity, and interpretability in machine learning.
| S-EPMC6584533 | biostudies-literature
Project description:BackgroundStroke is a significant global health concern, ranking as the second leading cause of death and placing a substantial financial burden on healthcare systems, particularly in low- and middle-income countries. Timely evaluation of stroke severity is crucial for predicting clinical outcomes, with standard assessment tools being the Rapid Arterial Occlusion Evaluation (RACE) and the National Institutes of Health Stroke Scale (NIHSS). This study aims to utilize Machine Learning (ML) algorithms to predict stroke severity using these two distinct scales.MethodsWe conducted this study using two datasets collected from hospitals in Urmia, Iran, corresponding to stroke severity assessments based on RACE and NIHSS. Seven ML algorithms were applied, including K-Nearest Neighbor (KNN), Decision Tree (DT), Random Forest (RF), Adaptive Boosting (AdaBoost), Extreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), and Artificial Neural Network (ANN). Hyperparameter tuning was performed using grid search to optimize model performance, and SHapley Additive Explanations (SHAP) were used to interpret the contribution of individual features.ResultsAmong the models, the RF achieved the highest performance, with accuracies of 92.68% for the RACE dataset and 91.19% for the NIHSS dataset. The Area Under the Curve (AUC) was 92.02% and 97.86% for the RACE and NIHSS datasets, respectively. The SHAP analysis identified triglyceride levels, length of hospital stay, and age as critical predictors of stroke severity.ConclusionsThis study is the first to apply ML models to the RACE and NIHSS scales for predicting stroke severity. The use of SHAP enhances the interpretability of the models, increasing clinicians' trust in these ML algorithms. The best-performing ML model can be a valuable tool for assisting medical professionals in predicting stroke severity in clinical settings.
| S-EPMC11562860 | biostudies-literature
Project description:BackgroundMultiple sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging and multimodal biomarkers to define the risk of disease activity.MethodsWe have analysed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centres, collecting disability scales at baseline and 2 years later. Imaging data included brain MRI and optical coherence tomography, and omics included genotyping, cytomics and phosphoproteomic data from peripheral blood mononuclear cells. Predictors of clinical outcomes were searched using Random Forest algorithms. Assessment of the algorithm performance was conducted in an independent prospective cohort of 271 MS patients from a single centre.ResultsWe found algorithms for predicting confirmed disability accumulation for the different scales, no evidence of disease activity (NEDA), onset of immunotherapy and the escalation from low- to high-efficacy therapy with intermediate to high-accuracy. This accuracy was achieved for most of the predictors using clinical data alone or in combination with imaging data. Still, in some cases, the addition of omics data slightly increased algorithm performance. Accuracies were comparable in both cohorts.ConclusionCombining clinical, imaging and omics data with machine learning helps identify MS patients at risk of disability worsening.
| S-EPMC10896787 | biostudies-literature
Project description:Accumulating diffusion tensor imaging (DTI) evidence suggests that white matter abnormalities evaluated by local diffusion homogeneity (LDH) or fractional anisotropy (FA) occur in patients with blepharospasm (BSP), both of which are significantly correlated with disease severity. However, whether the individual severity of BSP can be identified using these DTI metrics remains unknown. We aimed to investigate whether a combination of machine learning techniques and LDH or FA can accurately identify the individual severity of BSP. Forty-one patients with BSP were assessed using the Jankovic Rating Scale and DTI. The patients were assigned to non-functionally and functionally limited groups according to their Jankovic Rating Scale scores. A machine learning scheme consisting of beam search and support vector machines was designed to identify non-functionally versus functionally limited outcomes, with the input features being LDH or FA in 68 white matter regions. The proposed machine learning scheme with LDH or FA yielded an overall accuracy of 88.67 versus 85.19% in identifying non-functionally limited versus functionally limited outcomes. The scheme also identified a sensitivity of 91.40 versus 85.87% in correctly identifying functionally limited outcomes, a specificity of 83.33 versus 83.67% in accurately identifying non-functionally limited outcomes, and an area under the curve of 93.7 versus 91.3%. These findings suggest that a combination of LDH or FA measurements and a sophisticated machine learning scheme can accurately and reliably identify the individual disease severity in patients with BSP.
| S-EPMC8155629 | biostudies-literature
Project description:We present a mixed quantum-classical simulation of polariton dynamics for molecule-cavity hybrid systems. In particular, we treat the coupled electronic-photonic degrees of freedom (DOFs) as the quantum subsystem and the nuclear DOFs as the classical subsystem and use the trajectory surface hopping approach to simulate non-adiabatic dynamics among the polariton states due to the coupled motion of nuclei. We use the accurate nuclear gradient expression derived from the Pauli-Fierz quantum electrodynamics Hamiltonian without making further approximations. The energies, gradients, and derivative couplings of the molecular systems are obtained from the on-the-fly simulations at the level of complete active space self-consistent field (CASSCF), which are used to compute the polariton energies and nuclear gradients. The derivatives of dipoles are also necessary ingredients in the polariton nuclear gradient expression but are often not readily available in electronic structure methods. To address this challenge, we use a machine learning model with the Kernel ridge regression method to construct the dipoles and further obtain their derivatives, at the same level as the CASSCF theory. The cavity loss process is modeled with the Lindblad jump superoperator on the reduced density of the electronic-photonic quantum subsystem. We investigate the azomethane molecule and its photoinduced isomerization dynamics inside the cavity. Our results show the accuracy of the machine-learned dipoles and their usage in simulating polariton dynamics. Our polariton dynamics results also demonstrate the isomerization reaction of azomethane can be effectively tuned by coupling to an optical cavity and by changing the light-matter coupling strength and the cavity loss rate.
| S-EPMC10134431 | biostudies-literature
Project description:Phospholipidosis is an adverse effect caused by numerous cationic amphiphilic drugs and can affect many cell types. It is characterized by the excess accumulation of phospholipids and is most reliably identified by electron microscopy of cells revealing the presence of lamellar inclusion bodies. The development of phospholipidosis can cause a delay in the drug development process, and the importance of computational approaches to the problem has been well documented. Previous work on predictive methods for phospholipidosis showed that state of the art machine learning methods produced the best results. Here we extend this work by looking at a larger data set mined from the literature. We find that circular fingerprints lead to better models than either E-Dragon descriptors or a combination of the two. We also observe very similar performance in general between Random Forest and Support Vector Machine models.
| S-EPMC2949053 | biostudies-literature
Project description:Advances in DNA sequencing technologies have revolutionised rare disease diagnostics and have led to a dramatic increase in the volume of available genomic data. A key challenge that needs to be overcome to realise the full potential of these technologies is that of precisely predicting the effect of genetic variants on molecular and organismal phenotypes. Notably, despite recent progress, there is still a lack of robust in silico tools that accurately assign clinical significance to variants. Genetic alterations in the CACNA1F gene are the commonest cause of X-linked incomplete Congenital Stationary Night Blindness (iCSNB), a condition associated with non-progressive visual impairment. We combined genetic and homology modelling data to produce CACNA1F-vp, an in silico model that differentiates disease-implicated from benign missense CACNA1F changes. CACNA1F-vp predicts variant effects on the structure of the CACNA1F encoded protein (a calcium channel) using parameters based upon changes in amino acid properties; these include size, charge, hydrophobicity, and position. The model produces an overall score for each variant that can be used to predict its pathogenicity. CACNA1F-vp outperformed four other tools in identifying disease-implicated variants (area under receiver operating characteristic and precision recall curves = 0.84; Matthews correlation coefficient = 0.52) using a tenfold cross-validation technique. We consider this protein-specific model to be a robust stand-alone diagnostic classifier that could be replicated in other proteins and could enable precise and timely diagnosis.
| S-EPMC7608274 | biostudies-literature
Project description:Having accurate maps depicting the locations of residential buildings across a region benefits a range of sectors. This is particularly true for public health programs focused on delivering services at the household level, such as indoor residual spraying with insecticide to help prevent malaria. While open source data from OpenStreetMap (OSM) depicting the locations and shapes of buildings is rapidly improving in terms of quality and completeness globally, even in settings where all buildings have been mapped, information on whether these buildings are residential, commercial or another type is often only available for a small subset. Using OSM building data from Botswana and Swaziland, we identified buildings for which 'type' was indicated, generated via on the ground observations, and classified these into two classes, "sprayable" and "not-sprayable". Ensemble machine learning, using building characteristics such as size, shape and proximity to neighbouring features, was then used to form a model to predict which of these 2 classes every building in these two countries fell into. Results show that an ensemble machine learning approach performed marginally, but statistically, better than the best individual model and that using this ensemble model we were able to correctly classify >86% (using independent test data) of structures correctly as sprayable and not-sprayable across both countries.
| S-EPMC6150517 | biostudies-other
Project description:Hypertension is a widely prevalent disease and uncontrolled hypertension predisposes affected individuals to severe adverse effects. Though the importance of controlling hypertension is clear, the multitude of therapeutic regimens and patient factors that affect the success of blood pressure control makes it difficult to predict the likelihood to predict whether a patient's blood pressure will be controlled. This project endeavors to investigate whether machine learning can accurately predict the control of a patient's hypertension within 12 months of a clinical encounter. To build the machine learning model, a retrospective review of the electronic medical records of 350,008 patients 18 years of age and older between January 1, 2015 and June 1, 2022 was performed to form model training and testing cohorts. The data included in the model included medication combinations, patient laboratory values, vital sign measurements, comorbidities, healthcare encounters, and demographic information. The mean age of the patient population was 65.6 years with 161,283 (46.1%) men and 275,001 (78.6%) white. A sliding time window of data was used to both prohibit data leakage from training sets to test sets and to maximize model performance. This sliding window resulted in using the study data to create 287 predictive models each using 2 years of training data and one week of testing data for a total study duration of five and a half years. Model performance was combined across all models. The primary outcome, prediction of blood pressure control within 12 months demonstrated an area under the curve of 0.76 (95% confidence interval; 0.75-0.76), sensitivity of 61.52% (61.0-62.03%), specificity of 75.69% (75.25-76.13%), positive predictive value of 67.75% (67.51-67.99%), and negative predictive value of 70.49% (70.32-70.66%). An AUC of 0.756 is considered to be moderately good for machine learning models. While the accuracy of this model is promising, it is impossible to state with certainty the clinical relevancy of any clinical support ML model without deploying it in a clinical setting and studying its impact on health outcomes. By also incorporating uncertainty analysis for every prediction, the authors believe that this approach offers the best-known solution to predicting hypertension control and that machine learning may be able to improve the accuracy of hypertension control predictions using patient information already available in the electronic health record. This method can serve as a foundation with further research to strengthen the model accuracy and to help determine clinical relevance.
| S-EPMC10954144 | biostudies-literature
Project description:BackgroundThe incorporation of machine learning is becoming more prevalent in the clinical setting. By predicting clinical outcomes, machine learning can provide clinicians with a valuable tool for refining precision medicine approaches and improving treatment outcomes.MethodsThis was a post hoc analysis of pooled patient-level data from the global, real-world ACTION and ASCORE trials in patients with rheumatoid arthritis (RA) initiating abatacept. Patient demographic and disease characteristics were input across 10 machine learning models used to predict 12-month treatment retention. Retention was defined as treatment for > 365 days or ≤ 365 days in patients who achieved remission or major clinical response (based on European Alliance of Associations for Rheumatology response criteria). The pooled dataset was split into a training/validation cohort for model development and a test cohort for an unbiased evaluation of performance. SHapley Additive exPlanation (SHAP) values determined the level of importance and directionality for key patient features predicting abatacept retention.ResultsThe pooled ACTION and ASCORE dataset included 5320 patients with RA (mean [standard deviation] age 57.7 [12.7] years; 79% female). The 12-month abatacept retention rate was 61% (n = 3236) with a discontinuation rate of 39% (n = 2037). In the training set (n = 4218), the gradient-boosting classifier model demonstrated the best performance (testing accuracy: 62%). This model had an area under the receiver operating characteristic curve (95% confidence interval) of 0.620 (0.586, 0.653) and F1 score of 0.659 (0.625, 0.689) in the test set of patients (n = 1055). Using this model, the five most important variables predicting 12-month abatacept retention were low body mass index (BMI), low American College of Rheumatology functional status class, anti-citrullinated protein antibody (ACPA) positivity, low Patient Global Assessment, and younger age.ConclusionsThe gradient-boosting classifier model identified key patient features predictive of abatacept retention from this large, real-world study population. The SHAP values conveyed the directionality and importance of BMI, functional status, ACPA serostatus, Patient Global Assessment, and age for abatacept retention. Findings are consistent with previous observations and help validate the machine learning approach for predictive modelling in RA treatment, and may help inform clinical decision making.Trial registrationNCT02109666 (ACTION), NCT02090556 (ASCORE).
| S-EPMC11786492 | biostudies-literature