A novel machine learning-based approach for the computational functional assessment of pharmacogenomic variants View Full Text


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Article Info

DATE

2021-08-09

AUTHORS

Maria-Theodora Pandi, Maria Koromina, Iordanis Tsafaridis, Sotirios Patsilinakos, Evangelos Christoforou, Peter J. van der Spek, George P. Patrinos

ABSTRACT

BackgroundThe field of pharmacogenomics focuses on the way a person’s genome affects his or her response to a certain dose of a specified medication. The main aim is to utilize this information to guide and personalize the treatment in a way that maximizes the clinical benefits and minimizes the risks for the patients, thus fulfilling the promises of personalized medicine. Technological advances in genome sequencing, combined with the development of improved computational methods for the efficient analysis of the huge amount of generated data, have allowed the fast and inexpensive sequencing of a patient’s genome, hence rendering its incorporation into clinical routine practice a realistic possibility.MethodsThis study exploited thoroughly characterized in functional level SNVs within genes involved in drug metabolism and transport, to train a classifier that would categorize novel variants according to their expected effect on protein functionality. This categorization is based on the available in silico prediction and/or conservation scores, which are selected with the use of recursive feature elimination process. Toward this end, information regarding 190 pharmacovariants was leveraged, alongside with 4 machine learning algorithms, namely AdaBoost, XGBoost, multinomial logistic regression, and random forest, of which the performance was assessed through 5-fold cross validation.ResultsAll models achieved similar performance toward making informed conclusions, with RF model achieving the highest accuracy (85%, 95% CI: 0.79, 0.90), as well as improved overall performance (precision 85%, sensitivity 84%, specificity 94%) and being used for subsequent analyses. When applied on real world WGS data, the selected RF model identified 2 missense variants, expected to lead to decreased function proteins and 1 to increased. As expected, a greater number of variants were highlighted when the approach was used on NGS data derived from targeted resequencing of coding regions. Specifically, 71 variants (out of 156 with sufficient annotation information) were classified as to “Decreased function,” 41 variants as “No” function proteins, and 1 variant in “Increased function.”ConclusionOverall, the proposed RF-based classification model holds promise to lead to an extremely useful variant prioritization and act as a scoring tool with interesting clinical applications in the fields of pharmacogenomics and personalized medicine. More... »

PAGES

51

References to SciGraph publications

  • 2020-12-02. dbNSFP v4: a comprehensive database of transcript-specific functional predictions and annotations for human nonsynonymous and splice-site SNVs in GENOME MEDICINE
  • 2014-05-20. In silico comparative characterization of pharmacogenomic missense variants in BMC GENOMICS
  • 2018-09-12. An optimized prediction framework to assess the functional impact of pharmacogenetic variants in THE PHARMACOGENOMICS JOURNAL
  • 2002. Modern Applied Statistics with S in NONE
  • 2015-03-05. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology in GENETICS IN MEDICINE
  • 2015-07-31. Improving the Sequence Ontology terminology for genomic variant annotation in JOURNAL OF BIOMEDICAL SEMANTICS
  • 2001-10. Random Forests in MACHINE LEARNING
  • 2015-01-19. A method for calculating probabilities of fitness consequences for point mutations across the human genome in NATURE GENETICS
  • 2015-04-21. Clinical Association Between Pharmacogenomics and Adverse Drug Reactions in DRUGS
  • 2015-02-24. Pharmacogenomic information in drug labels: European Medicines Agency perspective in THE PHARMACOGENOMICS JOURNAL
  • 2016-04-21. Rare genetic variants in cellular transporters, metabolic enzymes, and nuclear receptors can be important determinants of interindividual differences in drug response in GENETICS IN MEDICINE
  • 2018-05-25. Integrating rare genetic variants into pharmacogenetic drug response predictions in HUMAN GENOMICS
  • 2017-10-26. Novel copy-number variations in pharmacogenes contribute to interindividual differences in drug pharmacokinetics in GENETICS IN MEDICINE
  • 2021-02-04. Prevalence of pharmacogenomic variants in 100 pharmacogenes among Southeast Asian populations under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm) in HUMAN GENOME VARIATION
  • 2016-01-04. A spectral approach integrating functional genomic annotations for coding and noncoding variants in NATURE GENETICS
  • 2015-10-14. Pharmacogenomics in the clinic in NATURE
  • 2017-11-27. Pharmacogenomic Biomarkers for Improved Drug Therapy—Recent Progress and Future Developments in THE AAPS JOURNAL
  • 2016-06-06. The Ensembl Variant Effect Predictor in GENOME BIOLOGY
  • 2010-04. A method and server for predicting damaging missense mutations in NATURE METHODS
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    36 schema:description BackgroundThe field of pharmacogenomics focuses on the way a person’s genome affects his or her response to a certain dose of a specified medication. The main aim is to utilize this information to guide and personalize the treatment in a way that maximizes the clinical benefits and minimizes the risks for the patients, thus fulfilling the promises of personalized medicine. Technological advances in genome sequencing, combined with the development of improved computational methods for the efficient analysis of the huge amount of generated data, have allowed the fast and inexpensive sequencing of a patient’s genome, hence rendering its incorporation into clinical routine practice a realistic possibility.MethodsThis study exploited thoroughly characterized in functional level SNVs within genes involved in drug metabolism and transport, to train a classifier that would categorize novel variants according to their expected effect on protein functionality. This categorization is based on the available in silico prediction and/or conservation scores, which are selected with the use of recursive feature elimination process. Toward this end, information regarding 190 pharmacovariants was leveraged, alongside with 4 machine learning algorithms, namely AdaBoost, XGBoost, multinomial logistic regression, and random forest, of which the performance was assessed through 5-fold cross validation.ResultsAll models achieved similar performance toward making informed conclusions, with RF model achieving the highest accuracy (85%, 95% CI: 0.79, 0.90), as well as improved overall performance (precision 85%, sensitivity 84%, specificity 94%) and being used for subsequent analyses. When applied on real world WGS data, the selected RF model identified 2 missense variants, expected to lead to decreased function proteins and 1 to increased. As expected, a greater number of variants were highlighted when the approach was used on NGS data derived from targeted resequencing of coding regions. Specifically, 71 variants (out of 156 with sufficient annotation information) were classified as to “Decreased function,” 41 variants as “No” function proteins, and 1 variant in “Increased function.”ConclusionOverall, the proposed RF-based classification model holds promise to lead to an extremely useful variant prioritization and act as a scoring tool with interesting clinical applications in the fields of pharmacogenomics and personalized medicine.
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