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Genome-wide association data classification and SNPs selection using two-stage quality-based Random Forests
- Source :
- BMC Genomics
- Publication Year :
- 2015
- Publisher :
- BioMed Central, 2015.
-
Abstract
- Background Single-nucleotide polymorphisms (SNPs) selection and identification are the most important tasks in Genome-wide association data analysis. The problem is difficult because genome-wide association data is very high dimensional and a large portion of SNPs in the data is irrelevant to the disease. Advanced machine learning methods have been successfully used in Genome-wide association studies (GWAS) for identification of genetic variants that have relatively big effects in some common, complex diseases. Among them, the most successful one is Random Forests (RF). Despite of performing well in terms of prediction accuracy in some data sets with moderate size, RF still suffers from working in GWAS for selecting informative SNPs and building accurate prediction models. In this paper, we propose to use a new two-stage quality-based sampling method in random forests, named ts-RF, for SNP subspace selection for GWAS. The method first applies p-value assessment to find a cut-off point that separates informative and irrelevant SNPs in two groups. The informative SNPs group is further divided into two sub-groups: highly informative and weak informative SNPs. When sampling the SNP subspace for building trees for the forest, only those SNPs from the two sub-groups are taken into account. The feature subspaces always contain highly informative SNPs when used to split a node at a tree. Results This approach enables one to generate more accurate trees with a lower prediction error, meanwhile possibly avoiding overfitting. It allows one to detect interactions of multiple SNPs with the diseases, and to reduce the dimensionality and the amount of Genome-wide association data needed for learning the RF model. Extensive experiments on two genome-wide SNP data sets (Parkinson case-control data comprised of 408,803 SNPs and Alzheimer case-control data comprised of 380,157 SNPs) and 10 gene data sets have demonstrated that the proposed model significantly reduced prediction errors and outperformed most existing the-state-of-the-art random forests. The top 25 SNPs in Parkinson data set were identified by the proposed model including four interesting genes associated with neurological disorders. Conclusion The presented approach has shown to be effective in selecting informative sub-groups of SNPs potentially associated with diseases that traditional statistical approaches might fail. The new RF works well for the data where the number of case-control objects is much smaller than the number of SNPs, which is a typical problem in gene data and GWAS. Experiment results demonstrated the effectiveness of the proposed RF model that outperformed the state-of-the-art RFs, including Breiman's RF, GRRF and wsRF methods.
- Subjects :
- Random Forests
Genome-wide association study
Data classification
Overfitting
Biology
computer.software_genre
Polymorphism, Single Nucleotide
Machine Learning
Alzheimer Disease
Genetics
Feature (machine learning)
Humans
Genetic Predisposition to Disease
Data mining
Selection (genetic algorithm)
Models, Genetic
Computational Biology
Reproducibility of Results
Parkinson Disease
SNPs Selection
Random forest
Data set
Tree (data structure)
Proceedings
computer
Algorithms
Biotechnology
Subjects
Details
- Language :
- English
- ISSN :
- 14712164
- Volume :
- 16
- Issue :
- Suppl 2
- Database :
- OpenAIRE
- Journal :
- BMC Genomics
- Accession number :
- edsair.doi.dedup.....66a59fca26e848060daa3d36536a137c