Drug response prediction model using a hierarchical structural component modeling method
- Title
- Drug response prediction model using a hierarchical structural component modeling method
- Author
- 최성경
- Keywords
- Biomarkers; Component-based structural equation modeling; Drug response; Liver cancer; Multiple reaction monitoring mass spectrometry (MRM-MS); Prediction model; Sorafenib
- Issue Date
- 2018-08
- Publisher
- BIOMED CENTRAL LTD
- Citation
- BMC BIOINFORMATICS, v. 19, Article no. 288
- Abstract
- Background: Component-based structural equation modeling methods are now widely used in science, business, education, and other fields. This method uses unobservable variables, i.e., "latent" variables, and structural equation model relationships between observable variables. Here, we applied this structural equation modeling method to biologically structured data. To identify candidate drug-response biomarkers, we first used proteomic peptide-level data, as measured by multiple reaction monitoring mass spectrometry (MRM-MS), for liver cancer patients. MRM-MS is a highly sensitive and selective method for proteomic targeted quantitation of peptide abundances in complex biological samples.
Results: We developed a component-based drug response prediction model, having the advantage that it first combines collapsed peptide-level data into protein-level information, facilitating subsequent biological interpretation. Our model also uses an alternating least squares algorithm, to efficiently estimate both coefficients of peptides and proteins. This approach also considers correlations between variables, without constraint, by a multiple testing problem. Using estimated peptide and protein coefficients, we selected significant protein biomarkers by permutation testing, resulting in our model for predicting liver cancer response to the tyrosine kinase inhibitor sorafenib.
Conclusions: Using data from a cohort of liver cancer patients, we then "fine-tuned" our model to successfully predict drug responses, as demonstrated by a high area under the curve (AUC) score. Such drug response prediction models may eventually find clinical translation in identifying individual patients likely to respond to specific therapies.
- URI
- https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-018-2270-7https://repository.hanyang.ac.kr/handle/20.500.11754/121450
- ISSN
- 1471-2105
- DOI
- 10.1186/s12859-018-2270-7
- Appears in Collections:
- COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > APPLIED MATHEMATICS(응용수학과) > Articles
- Files in This Item:
- 2018.08_최성경_Drug response prediction model using a hierarchical structural component modeling method.pdfDownload
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