Academic Journal
Unified Cox model based multifactor dimensionality reduction method for gene-gene interaction analysis of the survival phenotype
| العنوان: | Unified Cox model based multifactor dimensionality reduction method for gene-gene interaction analysis of the survival phenotype |
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| المؤلفون: | Lee, Seungyeoun, Son, Donghee, Kim, Yongkang, Yu, Wenbao, Park, Taesung |
| المساهمون: | 이승연, 손동희, 김영강, 박태성 |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2018 |
| المجموعة: | Seoul National University: S-Space |
| مصطلحات موضوعية: | Survival time, Cox model, Multifactor dimensionality reduction method, Gene-gene interaction, Unified model based method |
| الوصف: | Background One strategy for addressing missing heritability in genome-wide association study is gene-gene interaction analysis, which, unlike a single gene approach, involves high-dimensionality. The multifactor dimensionality reduction method (MDR) has been widely applied to reduce multi-levels of genotypes into high or low risk groups. The Cox-MDR method has been proposed to detect gene-gene interactions associated with the survival phenotype by using the martingale residuals from a Cox model. However, this method requires a cross-validation procedure to find the best SNP pair among all possible pairs and the permutation procedure should be followed for the significance of gene-gene interactions. Recently, the unified model based multifactor dimensionality reduction method (UM-MDR) has been proposed to unify the significance testing with the MDR algorithm within the regression model framework, in which neither cross-validation nor permutation testing are needed. In this paper, we proposed a simple approach, called Cox UM-MDR, which combines Cox-MDR with the key procedure of UM-MDR to identify gene-gene interactions associated with the survival phenotype. Results The simulation study was performed to compare Cox UM-MDR with Cox-MDR with and without the marginal effects of SNPs. We found that Cox UM-MDR has similar power to Cox-MDR without marginal effects, whereas it outperforms Cox-MDR with marginal effects and more robust to heavy censoring. We also applied Cox UM-MDR to a dataset of leukemia patients and detected gene-gene interactions with regard to the survival time. Conclusion Cox UM-MDR is easily implemented by combining Cox-MDR with UM-MDR to detect the significant gene-gene interactions associated with the survival time without cross-validation and permutation testing. The simulation results are shown to demonstrate the utility of the proposed method, which achieves at least the same power as Cox-MDR in most scenarios, and outperforms Cox-MDR when some SNPs having only marginal effects might mask the ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1756-0381 |
| Relation: | BioData Mining, 11(1):27; http://hdl.handle.net/10371/146979 |
| DOI: | 10.1186/s13040-018-0189-1 |
| الاتاحة: | http://hdl.handle.net/10371/146979 https://doi.org/10.1186/s13040-018-0189-1 |
| Rights: | The Author(s). |
| رقم الانضمام: | edsbas.A02E6405 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17560381 |
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| DOI: | 10.1186/s13040-018-0189-1 |