Towards a New Qualitative Screening Assay for Synthetic Cannabinoids Using Metabolomics and Machine Learning.

BACKGROUND: Synthetic cannabinoids (SCs) are steadily emerging on the drug market. To remain competitive in clinical or forensic toxicology, new screening strategies including high-resolution mass spectrometry (HRMS) are required. Machine learning algorithms can detect and learn chemical signatures...

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Published in:Clinical Chemistry Vol. 68; no. 6; pp. 848 - 856
Main Authors: Streun, Gabriel L., Steuer, Andrea E., Poetzsch, Sandra N., Ebert, Lars C., Dobay, Akos, Kraemer, Thomas
Format: Journal Article
Published: Oxford University Press / USA Jun2022
Online Access:View this record in EBSCOhost
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      dt: Jun2022
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      pub: Oxford University Press / USA
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        10.1093/clinchem/hvac045
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        atl: Towards a New Qualitative Screening Assay for Synthetic Cannabinoids Using Metabolomics and Machine Learning.
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          Streun, Gabriel L.
          Steuer, Andrea E.
          Poetzsch, Sandra N.
          Ebert, Lars C.
          Dobay, Akos
          Kraemer, Thomas
        affil: Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland
      sug:
      ab: BACKGROUND: Synthetic cannabinoids (SCs) are steadily emerging on the drug market. To remain competitive in clinical or forensic toxicology, new screening strategies including high-resolution mass spectrometry (HRMS) are required. Machine learning algorithms can detect and learn chemical signatures in complex datasets and use them as a proxy to predict new samples. We propose a new screening tool based on a SC-specific change of the metabolome and a machine learning algorithm. METHODS: Authentic human urine samples (n=474), positive or negative for SCs, were used. These samples were measured with an untargeted metabolomics liquid chromatography (LC)-quadrupole time-of-flight-HRMS method. Progenesis QI software was used to preprocess the raw data. Following feature engineering, a random forest (RF) model was optimized in R using a 10-fold cross-validation method and a training set (n=369). The performance of the model was assessed with a test (n=50) and a verification (n=55) set. RESULTS: During RF optimization, 49 features, 200 trees, and 7 variables at each branching node were determined as most predictive. The optimized model accuracy, clinical sensitivity, clinical specificity, positive predictive value, and negative predictive value were 88.1%, 83.0%, 92.7%, 91.3%, and 85.6%, respectively. The test set was predicted with an accuracy of 88.0%, and the verification set provided evidence that the model was able to detect cannabinoid-specific changes in the metabolome. CONCLUSIONS: An RF approach combined with metabolomics enables a novel screening strategy for responding effectively to the challenge of new SCs. Biomarkers identified by this approach may also be integrated in routine screening methods.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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