scholarly journals Machine learning guided association of adverse drug reactions with in vitro target-based pharmacology

2019 ◽  
Author(s):  
Robert Ietswaart ◽  
Seda Arat ◽  
Amanda X. Chen ◽  
Saman Farahmand ◽  
Bumjun Kim ◽  
...  
Keyword(s):  
Machine Learning ◽  
Adverse Drug Reactions ◽  
Drug Targets ◽  
Bile Acid Metabolism ◽  
Drug Reactions ◽  
Machine Learning Approach ◽  
Forest Models ◽  
Random Forest Models ◽  
Model Features

AbstractAdverse drug reactions (ADRs) are one of the leading causes of morbidity and mortality in health care. Understanding which drug targets are linked to ADRs can lead to the development of safer medicines. Here, we analyze in vitro secondary pharmacology of common (off) targets for 2134 marketed drugs. To associate these drugs with human ADRs, we utilized FDA Adverse Event Reports and developed random forest models that predict ADR occurrences from in vitro pharmacological profiles. By evaluating Gini importance scores of model features, we identify 221 target-ADR associations, which co-occur in PubMed abstracts to a greater extent than expected by chance. Among these are established relations, such as the association of in vitro hERG binding with cardiac arrhythmias, which further validate our machine learning approach. Evidence on bile acid metabolism supports our identification of associations between the Bile Salt Export Pump and renal, thyroid, lipid metabolism, respiratory tract and central nervous system disorders. Unexpectedly, our model suggests PDE3 is associated with 40 ADRs. These associations provide a comprehensive resource to support drug development and human biology studies.

scholarly journals A multi-step machine learning approach to assess the impact of COVID-19 lockdown on NO2 attributable deaths in Milan and Rome, Italy

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Luca Boniardi ◽  
Federica Nobile ◽  
Massimo Stafoggia ◽  
Paola Michelozzi ◽  
Carla Ancona
Keyword(s):  
Machine Learning ◽  
Land Use ◽  
Air Pollution ◽  
Random Forest ◽  
Citizen Science ◽  
Learning Approach ◽  
Machine Learning Approach ◽  
Forest Models ◽  
Random Forest Models ◽  
The Impact

Abstract Background Air pollution is one of the main concerns for the health of European citizens, and cities are currently striving to accomplish EU air pollution regulation. The 2020 COVID-19 lockdown measures can be seen as an unintended but effective experiment to assess the impact of traffic restriction policies on air pollution. Our objective was to estimate the impact of the lockdown measures on NO2 concentrations and health in the two largest Italian cities. Methods NO2 concentration datasets were built using data deriving from a 1-month citizen science monitoring campaign that took place in Milan and Rome just before the Italian lockdown period. Annual mean NO2 concentrations were estimated for a lockdown scenario (Scenario 1) and a scenario without lockdown (Scenario 2), by applying city-specific annual adjustment factors to the 1-month data. The latter were estimated deriving data from Air Quality Network stations and by applying a machine learning approach. NO2 spatial distribution was estimated at a neighbourhood scale by applying Land Use Random Forest models for the two scenarios. Finally, the impact of lockdown on health was estimated by subtracting attributable deaths for Scenario 1 and those for Scenario 2, both estimated by applying literature-based dose–response function on the counterfactual concentrations of 10 μg/m3. Results The Land Use Random Forest models were able to capture 41–42% of the total NO2 variability. Passing from Scenario 2 (annual NO2 without lockdown) to Scenario 1 (annual NO2 with lockdown), the population-weighted exposure to NO2 for Milan and Rome decreased by 15.1% and 15.3% on an annual basis. Considering the 10 μg/m3 counterfactual, prevented deaths were respectively 213 and 604. Conclusions Our results show that the lockdown had a beneficial impact on air quality and human health. However, compliance with the current EU legal limit is not enough to avoid a high number of NO2 attributable deaths. This contribution reaffirms the potentiality of the citizen science approach and calls for more ambitious traffic calming policies and a re-evaluation of the legal annual limit value for NO2 for the protection of human health.

scholarly journals A Multimodality Machine Learning Approach to Differentiate Severe and Nonsevere COVID-19: Model Development and Validation

10.2196/23948 ◽  
2021 ◽  
Vol 23 (4) ◽  
pp. e23948
Author(s):  
Yuanfang Chen ◽  
Liu Ouyang ◽  
Forrest S Bao ◽  
Qian Li ◽  
Lei Han ◽  
...  
Keyword(s):  
Machine Learning ◽  
Random Forest ◽  
Laboratory Test ◽  
Predictive Accuracy ◽  
Learning Approach ◽  
Test Results ◽  
Laboratory Test Results ◽  
Machine Learning Approach ◽  
Forest Models ◽  
Random Forest Models

Background Effectively and efficiently diagnosing patients who have COVID-19 with the accurate clinical type of the disease is essential to achieve optimal outcomes for the patients as well as to reduce the risk of overloading the health care system. Currently, severe and nonsevere COVID-19 types are differentiated by only a few features, which do not comprehensively characterize the complicated pathological, physiological, and immunological responses to SARS-CoV-2 infection in the different disease types. In addition, these type-defining features may not be readily testable at the time of diagnosis. Objective In this study, we aimed to use a machine learning approach to understand COVID-19 more comprehensively, accurately differentiate severe and nonsevere COVID-19 clinical types based on multiple medical features, and provide reliable predictions of the clinical type of the disease. Methods For this study, we recruited 214 confirmed patients with nonsevere COVID-19 and 148 patients with severe COVID-19. The clinical characteristics (26 features) and laboratory test results (26 features) upon admission were acquired as two input modalities. Exploratory analyses demonstrated that these features differed substantially between two clinical types. Machine learning random forest models based on all the features in each modality as well as on the top 5 features in each modality combined were developed and validated to differentiate COVID-19 clinical types. Results Using clinical and laboratory results independently as input, the random forest models achieved >90% and >95% predictive accuracy, respectively. The importance scores of the input features were further evaluated, and the top 5 features from each modality were identified (age, hypertension, cardiovascular disease, gender, and diabetes for the clinical features modality, and dimerized plasmin fragment D, high sensitivity troponin I, absolute neutrophil count, interleukin 6, and lactate dehydrogenase for the laboratory testing modality, in descending order). Using these top 10 multimodal features as the only input instead of all 52 features combined, the random forest model was able to achieve 97% predictive accuracy. Conclusions Our findings shed light on how the human body reacts to SARS-CoV-2 infection as a unit and provide insights on effectively evaluating the disease severity of patients with COVID-19 based on more common medical features when gold standard features are not available. We suggest that clinical information can be used as an initial screening tool for self-evaluation and triage, while laboratory test results should be applied when accuracy is the priority.

scholarly journals Machine learning guided association of adverse drug reactions with in vitro target-based pharmacology

EBioMedicine ◽  
2020 ◽  
Vol 57 ◽  
pp. 102837 ◽  
Author(s):  
Robert Ietswaart ◽  
Seda Arat ◽  
Amanda X. Chen ◽  
Saman Farahmand ◽  
Bumjun Kim ◽  
...  
Keyword(s):  
Machine Learning ◽  
Adverse Drug Reactions ◽  
Drug Reactions

scholarly journals Data-Driven Wildfire Risk Prediction in Northern California

Atmosphere ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 109
Author(s):  
Ashima Malik ◽  
Megha Rajam Rao ◽  
Nandini Puppala ◽  
Prathusha Koouri ◽  
Venkata Anil Kumar Thota ◽  
...  
Keyword(s):  
Machine Learning ◽  
Random Forest ◽  
Learning Curves ◽  
Data Driven ◽  
Northern California ◽  
Combined Model ◽  
Wildfire Risk ◽  
Study Results ◽  
Forest Models ◽  
Random Forest Models

Over the years, rampant wildfires have plagued the state of California, creating economic and environmental loss. In 2018, wildfires cost nearly 800 million dollars in economic loss and claimed more than 100 lives in California. Over 1.6 million acres of land has burned and caused large sums of environmental damage. Although, recently, researchers have introduced machine learning models and algorithms in predicting the wildfire risks, these results focused on special perspectives and were restricted to a limited number of data parameters. In this paper, we have proposed two data-driven machine learning approaches based on random forest models to predict the wildfire risk at areas near Monticello and Winters, California. This study demonstrated how the models were developed and applied with comprehensive data parameters such as powerlines, terrain, and vegetation in different perspectives that improved the spatial and temporal accuracy in predicting the risk of wildfire including fire ignition. The combined model uses the spatial and the temporal parameters as a single combined dataset to train and predict the fire risk, whereas the ensemble model was fed separate parameters that were later stacked to work as a single model. Our experiment shows that the combined model produced better results compared to the ensemble of random forest models on separate spatial data in terms of accuracy. The models were validated with Receiver Operating Characteristic (ROC) curves, learning curves, and evaluation metrics such as: accuracy, confusion matrices, and classification report. The study results showed and achieved cutting-edge accuracy of 92% in predicting the wildfire risks, including ignition by utilizing the regional spatial and temporal data along with standard data parameters in Northern California.

scholarly journals Application of multi-omics data integration and machine learning approaches to identify epigenetic and transcriptomic differences between in vitro and in vivo produced bovine embryos

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252096
Author(s):  
Maria B. Rabaglino ◽  
Alan O’Doherty ◽  
Jan Bojsen-Møller Secher ◽  
Patrick Lonergan ◽  
Poul Hyttel ◽  
...  
Keyword(s):  
Machine Learning ◽  
Data Integration ◽  
Focal Adhesion ◽  
Learning Approach ◽  
Omics Data ◽  
Machine Learning Approach ◽  
Cluster 2 ◽  
Omics Data Integration

Pregnancy rates for in vitro produced (IVP) embryos are usually lower than for embryos produced in vivo after ovarian superovulation (MOET). This is potentially due to alterations in their trophectoderm (TE), the outermost layer in physical contact with the maternal endometrium. The main objective was to apply a multi-omics data integration approach to identify both temporally differentially expressed and differentially methylated genes (DEG and DMG), between IVP and MOET embryos, that could impact TE function. To start, four and five published transcriptomic and epigenomic datasets, respectively, were processed for data integration. Second, DEG from day 7 to days 13 and 16 and DMG from day 7 to day 17 were determined in the TE from IVP vs. MOET embryos. Third, genes that were both DE and DM were subjected to hierarchical clustering and functional enrichment analysis. Finally, findings were validated through a machine learning approach with two additional datasets from day 15 embryos. There were 1535 DEG and 6360 DMG, with 490 overlapped genes, whose expression profiles at days 13 and 16 resulted in three main clusters. Cluster 1 (188) and Cluster 2 (191) genes were down-regulated at day 13 or day 16, respectively, while Cluster 3 genes (111) were up-regulated at both days, in IVP embryos compared to MOET embryos. The top enriched terms were the KEGG pathway "focal adhesion" in Cluster 1 (FDR = 0.003), and the cellular component: "extracellular exosome" in Cluster 2 (FDR<0.0001), also enriched in Cluster 1 (FDR = 0.04). According to the machine learning approach, genes in Cluster 1 showed a similar expression pattern between IVP and less developed (short) MOET conceptuses; and between MOET and DKK1-treated (advanced) IVP conceptuses. In conclusion, these results suggest that early conceptuses derived from IVP embryos exhibit epigenomic and transcriptomic changes that later affect its elongation and focal adhesion, impairing post-transfer survival.

scholarly journals Applicability of an Automated Model and Parameter Selection in the Prediction of Screening-Level PTSD in Danish Soldiers Following Deployment: Development Study of Transferable Predictive Models Using Automated Machine Learning (Preprint)

2019 ◽  
Author(s):  
Karen-Inge Karstoft ◽  
Ioannis Tsamardinos ◽  
Kasper Eskelund ◽  
Søren Bo Andersen ◽  
Lars Ravnborg Nissen
Keyword(s):  
Machine Learning ◽  
Operating Characteristic ◽  
Linear Models ◽  
Prediction Models ◽  
Characteristic Curve ◽  
Ptsd Symptoms ◽  
Forest Models ◽  
Random Forest Models ◽  
Automated Machine Learning ◽  
Military Rank

BACKGROUND Posttraumatic stress disorder (PTSD) is a relatively common consequence of deployment to war zones. Early postdeployment screening with the aim of identifying those at risk for PTSD in the years following deployment will help deliver interventions to those in need but have so far proved unsuccessful. OBJECTIVE This study aimed to test the applicability of automated model selection and the ability of automated machine learning prediction models to transfer across cohorts and predict screening-level PTSD 2.5 years and 6.5 years after deployment. METHODS Automated machine learning was applied to data routinely collected 6-8 months after return from deployment from 3 different cohorts of Danish soldiers deployed to Afghanistan in 2009 (cohort 1, N=287 or N=261 depending on the timing of the outcome assessment), 2010 (cohort 2, N=352), and 2013 (cohort 3, N=232). RESULTS Models transferred well between cohorts. For screening-level PTSD 2.5 and 6.5 years after deployment, random forest models provided the highest accuracy as measured by area under the receiver operating characteristic curve (AUC): 2.5 years, AUC=0.77, 95% CI 0.71-0.83; 6.5 years, AUC=0.78, 95% CI 0.73-0.83. Linear models performed equally well. Military rank, hyperarousal symptoms, and total level of PTSD symptoms were highly predictive. CONCLUSIONS Automated machine learning provided validated models that can be readily implemented in future deployment cohorts in the Danish Defense with the aim of targeting postdeployment support interventions to those at highest risk for developing PTSD, provided the cohorts are deployed on similar missions.

For Honor, for Toxicity

2021 ◽  
Vol 5 (CHI PLAY) ◽  
pp. 1-29
Author(s):  
Alessandro Canossa ◽  
Dmitry Salimov ◽  
Ahmad Azadvar ◽  
Casper Harteveld ◽  
Georgios Yannakakis
Keyword(s):  
Machine Learning ◽  
Random Forest ◽  
Random Forests ◽  
Initial Study ◽  
Unfair Advantage ◽  
Offensive Behavior ◽  
Forest Models ◽  
Random Forest Models ◽  
Action Type ◽  
Degree Of Severity

Is it possible to detect toxicity in games just by observing in-game behavior? If so, what are the behavioral factors that will help machine learning to discover the unknown relationship between gameplay and toxic behavior? In this initial study, we examine whether it is possible to predict toxicity in the MOBA gameFor Honor by observing in-game behavior for players that have been labeled as toxic (i.e. players that have been sanctioned by Ubisoft community managers). We test our hypothesis of detecting toxicity through gameplay with a dataset of almost 1,800 sanctioned players, and comparing these sanctioned players with unsanctioned players. Sanctioned players are defined by their toxic action type (offensive behavior vs. unfair advantage) and degree of severity (warned vs. banned). Our findings, based on supervised learning with random forests, suggest that it is not only possible to behaviorally distinguish sanctioned from unsanctioned players based on selected features of gameplay; it is also possible to predict both the sanction severity (warned vs. banned) and the sanction type (offensive behavior vs. unfair advantage). In particular, all random forest models predict toxicity, its severity, and type, with an accuracy of at least 82%, on average, on unseen players. This research shows that observing in-game behavior can support the work of community managers in moderating and possibly containing the burden of toxic behavior.

Sign in / Sign up

Export Citation Format

Share Document