title: A novel Markov Blanket-based repeated-fishing strategy for capturing phenotype-related biomarkers in big omics data.
abstract: BACKGROUND
  We propose a novel Markov Blanket-based repeated-fishing strategy (MBRFS) in attempt to increase the power of existing Markov Blanket method (DASSO-MB) and maintain its advantages in omic data analysis.
  
  
  RESULTS
  Both simulation and real data analysis were conducted to assess its performances by comparing with other methods including χ(2) test with Bonferroni and B-H adjustment, least absolute shrinkage and selection operator (LASSO) and DASSO-MB. A serious of simulation studies showed that the true discovery rate (TDR) of proposed MBRFS was always close to zero under null hypothesis (odds ratio = 1 for each SNPs) with excellent stability in all three scenarios of independent phenotype-related SNPs without linkage disequilibrium (LD) around them, correlated phenotype-related SNPs without LD around them, and phenotype-related SNPs with strong LD around them. As expected, under different odds ratio and minor allel frequency (MAFs), MBRFS always had the best performances in capturing the true phenotype-related biomarkers with higher matthews correlation coefficience (MCC) for all three scenarios above. More importantly, since proposed MBRFS using the repeated fishing strategy, it still captures more phenotype-related SNPs with minor effects when non-significant phenotype-related SNPs emerged under χ(2) test after Bonferroni multiple correction. The various real omics data analysis, including GWAS data, DNA methylation data, gene expression data and metabolites data, indicated that the proposed MBRFS always detected relatively reasonable biomarkers.
  
  
  CONCLUSIONS
  Our proposed MBRFS can exactly capture the true phenotype-related biomarkers with the reduction of false negative rate when the phenotype-related biomarkers are independent or correlated, as well as the circumstance that phenotype-related biomarkers are associated with non-phenotype-related ones.
authors.affiliation: Department of biostatistics, School of Public Health, Shandong University, Jinan City, Shandong Province, P. R. China. lihongkaiyouxiang@163.com.
authors.forename: Hongkai
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of biostatistics, School of Public Health, Shandong University, Jinan City, Shandong Province, P. R. China. yuanzhongshang@sdu.edu.cn.
authors.forename: Zhongshang
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of biostatistics, School of Public Health, Shandong University, Jinan City, Shandong Province, P. R. China. jjdjijiadong@163.com.
authors.forename: Jiadong
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of biostatistics, School of Public Health, Shandong University, Jinan City, Shandong Province, P. R. China. xujinghello@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of biostatistics, School of Public Health, Shandong University, Jinan City, Shandong Province, P. R. China. zt2730@foxmail.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of biostatistics, School of Public Health, Shandong University, Jinan City, Shandong Province, P. R. China. zhxiaoshuai@gmail.com.
authors.forename: Xiaoshuai
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of biostatistics, School of Public Health, Shandong University, Jinan City, Shandong Province, P. R. China. xuefzh@sdu.edu.cn.
authors.forename: Fuzhong
authors.initials: F
authors.lastname: Xue
mesh_terms: D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics; D016022:Case-Control Studies; D003198:Computer Simulation; D019175:DNA Methylation; D030541:Databases, Genetic; D005787:Gene Frequency; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods*; D006801:Humans; D007918:Leprosy / Q000175:diagnosis / Q000235:genetics; D015810:Linkage Disequilibrium; D008390:Markov Chains; D008962:Models, Theoretical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics
chemical_list: D005819:Genetic Markers