Machine learning on a genome-wide association study to predict late genitourinary toxicity after prostate radiation therapy Journal Article


Authors: Lee, S.; Kerns, S.; Ostrer, H.; Rosenstein, B.; Deasy, J. O.; Oh, J. H.
Article Title: Machine learning on a genome-wide association study to predict late genitourinary toxicity after prostate radiation therapy
Abstract: Purpose: Late genitourinary (GU) toxicity after radiation therapy limits the quality of life of prostate cancer survivors; however, efforts to explain GU toxicity using patient and dose information have remained unsuccessful. We identified patients with a greater congenital GU toxicity risk by identifying and integrating patterns in genome-wide single nucleotide polymorphisms (SNPs). Methods and Materials: We applied a preconditioned random forest regression method for predicting risk from the genome-wide data to combine the effects of multiple SNPs and overcome the statistical power limitations of single-SNP analysis. We studied a cohort of 324 prostate cancer patients who were self-assessed for 4 urinary symptoms at 2 years after radiation therapy using the International Prostate Symptom Score. Results: The predictive accuracy of the method varied across the symptoms. Only for the weak stream endpoint did it achieve a significant area under the curve of 0.70 (95% confidence interval 0.54-0.86; P =.01) on hold-out validation data that outperformed competing methods. Gene ontology analysis highlighted key biological processes, such as neurogenesis and ion transport, from the genes known to be important for urinary tract functions. Conclusions: We applied machine learning methods and bioinformatics tools to genome-wide data to predict and explain GU toxicity. Our approach enabled the design of a more powerful predictive model and the determination of plausible biomarkers and biological processes associated with GU toxicity. © 2018 Elsevier Inc.
Keywords: genes; radiotherapy; risk assessment; single nucleotide polymorphisms; artificial intelligence; urology; forecasting; patient treatment; toxicity; regression analysis; decision trees; diseases; learning systems; methods and materials; genome-wide association studies; area under the curves; applied machine learning; bioinformatics tools; genitourinary toxicities; international prostate symptom scores
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 101
Issue: 1
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2018-05-01
Start Page: 128
End Page: 135
Language: English
DOI: 10.1016/j.ijrobp.2018.01.054
PROVIDER: scopus
PMCID: PMC5886789
PUBMED: 29502932
DOI/URL:
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Jung Hun Oh
    187 Oh
  2. Joseph Owen Deasy
    524 Deasy
  3. Sang Kyu Lee
    18 Lee