Cox-based MDR (CoxMDR) [37] U U U U U No No No

Cox-based MDR (CoxMDR) [37] U U U U U No No No No Yes D, Q, MV D D D D No Yes Yes Yes NoMultivariate GMDR (MVGMDR) [38] Robust MDR (RMDR) [39]Blood pressure [38] Bladder cancer [39] Alzheimer’s disease [40] Chronic Fatigue Syndrome [41]Log-linear-based MDR (LM-MDR) [40] Odds-ratio-based MDR (OR-MDR) [41] Optimal MDR (Opt-MDR) [42] U NoMDR for Stratified Populations (MDR-SP) [43] UDNoPair-wise MDR (PW-MDR) [44]Simultaneous handling of families and unrelateds Transformation of survival time into dichotomous attribute using martingale residuals Multivariate modeling utilizing generalized estimating equations Handling of sparse/empty cells employing `unknown risk’ class Improved factor mixture by log-linear models and re-classification of threat OR rather of naive Bayes classifier to ?classify its danger Information driven rather of fixed threshold; Pvalues approximated by generalized EVD alternatively of permutation test Accounting for population stratification by using principal elements; significance estimation by generalized EVD Handling of sparse/empty cells by reducing contingency tables to all achievable two-dimensional interactions No D U No DYesKidney transplant [44]NoEvaluation from the classification result Extended MDR (EMDR) Evaluation of final model by v2 statistic; [45] consideration of different permutation methods Various phenotypes or information structures Survival Dimensionality Classification according to variations beReduction (SDR) [46] tween cell and complete population survival estimates; IBS to evaluate modelsUNoSNoRheumatoid arthritis [46]continuedTable 1. (Continued) Information structure Cov Pheno Compact sample sizesa No No ApplicationsNameDescriptionU U No QNoSBladder cancer [47] Renal and Vascular EndStage Disease [48] Obesity [49]Survival MDR (Surv-MDR) a0023781 [47] Quantitative MDR (QMDR) [48] U No O NoOrdinal MDR (Ord-MDR) [49] F No DLog-rank test to classify cells; squared log-rank statistic to evaluate models dar.12324 Handling of quantitative phenotypes by comparing cell with overall imply; t-test to evaluate models Handling of phenotypes with >2 classes by assigning each and every cell to probably phenotypic class Handling of extended pedigrees making use of pedigree disequilibrium test No F No D SB-497115GR NoAlzheimer’s illness [50]MDR with Pedigree Disequilibrium Test (MDR-PDT) [50] MDR with Phenomic Evaluation (MDRPhenomics) [51]Autism [51]Aggregated MDR (A-MDR) [52]UNoDNoJuvenile idiopathic arthritis [52]Model-based MDR (MBMDR) [53]Handling of trios by comparing variety of occasions genotype is transmitted versus not transmitted to impacted youngster; analysis of variance model to assesses impact of Computer Defining substantial models making use of threshold maximizing region below ROC curve; aggregated risk score based on all significant models Test of every single cell versus all other people using association test statistic; association test statistic comparing pooled highrisk and pooled low-risk cells to evaluate models U NoD, Q, SNoBladder cancer [53, 54], Crohn’s disease [55, 56], blood pressure [57]Cov ?Covariate adjustment achievable, Pheno ?Feasible phenotypes with D ?Dichotomous, Q ?Quantitative, S ?Survival, MV ?Multivariate, O ?Ordinal.Information structures: F ?Family members primarily based, U ?Unrelated samples.A roadmap to multifactor dimensionality reduction methodsaBasically, MDR-based approaches are created for little sample sizes, but some procedures give unique approaches to handle sparse or empty cells, commonly arising when analyzing really tiny sample sizes.||Gola et al.Table 2. Implementations of MDR-based solutions Metho.Cox-based MDR (CoxMDR) [37] U U U U U No No No No Yes D, Q, MV D D D D No Yes Yes Yes NoMultivariate GMDR (MVGMDR) [38] Robust MDR (RMDR) [39]Blood stress [38] Bladder cancer [39] Alzheimer’s disease [40] Chronic Fatigue Syndrome [41]Log-linear-based MDR (LM-MDR) [40] Odds-ratio-based MDR (OR-MDR) [41] Optimal MDR (Opt-MDR) [42] U NoMDR for Stratified Populations (MDR-SP) [43] UDNoPair-wise MDR (PW-MDR) [44]Simultaneous handling of families and unrelateds Transformation of survival time into dichotomous attribute applying martingale residuals Multivariate modeling employing generalized estimating equations Handling of sparse/empty cells working with `unknown risk’ class Enhanced element mixture by log-linear models and re-classification of danger OR rather of naive Bayes classifier to ?classify its danger Data driven rather of fixed threshold; Pvalues approximated by generalized EVD rather of permutation test Accounting for population stratification by utilizing principal elements; significance estimation by generalized EVD Handling of sparse/empty cells by minimizing contingency tables to all attainable two-dimensional interactions No D U No DYesKidney transplant [44]NoEvaluation of the classification result Extended MDR (EMDR) Evaluation of final model by v2 statistic; [45] consideration of various permutation tactics Diverse phenotypes or information structures Survival Dimensionality Classification based on variations beReduction (SDR) [46] tween cell and complete population survival estimates; IBS to evaluate modelsUNoSNoRheumatoid arthritis [46]continuedTable 1. (Continued) Information structure Cov Pheno Small sample sizesa No No ApplicationsNameDescriptionU U No QNoSBladder cancer [47] Renal and Vascular EndStage Illness [48] Obesity [49]Survival MDR (Surv-MDR) a0023781 [47] Quantitative MDR (QMDR) [48] U No O NoOrdinal MDR (Ord-MDR) [49] F No DLog-rank test to classify cells; squared log-rank statistic to evaluate models dar.12324 Handling of quantitative phenotypes by comparing cell with all round imply; t-test to evaluate models Handling of phenotypes with >2 classes by assigning every cell to probably phenotypic class Handling of extended pedigrees utilizing pedigree disequilibrium test No F No D NoAlzheimer’s disease [50]MDR with Pedigree Disequilibrium Test (MDR-PDT) [50] MDR with Phenomic Evaluation (MDRPhenomics) [51]Autism [51]Aggregated MDR (A-MDR) [52]UNoDNoJuvenile idiopathic arthritis [52]Model-based MDR (MBMDR) [53]Handling of trios by comparing INK1197 site quantity of instances genotype is transmitted versus not transmitted to affected kid; analysis of variance model to assesses impact of Computer Defining considerable models using threshold maximizing location below ROC curve; aggregated threat score according to all significant models Test of each cell versus all other people employing association test statistic; association test statistic comparing pooled highrisk and pooled low-risk cells to evaluate models U NoD, Q, SNoBladder cancer [53, 54], Crohn’s illness [55, 56], blood pressure [57]Cov ?Covariate adjustment possible, Pheno ?Feasible phenotypes with D ?Dichotomous, Q ?Quantitative, S ?Survival, MV ?Multivariate, O ?Ordinal.Information structures: F ?Loved ones based, U ?Unrelated samples.A roadmap to multifactor dimensionality reduction methodsaBasically, MDR-based techniques are made for little sample sizes, but some techniques supply unique approaches to take care of sparse or empty cells, typically arising when analyzing very small sample sizes.||Gola et al.Table 2. Implementations of MDR-based approaches Metho.