Genome-wide association filtering using a highly locus-specific transmission/disequilibrium test

Multimarker transmission/disequilibrium tests (TDTs) are powerful association and linkage tests used to perform genome-wide filtering in the search for disease susceptibility loci. In contrast to case/control studies, they have a low rate of false positives for population stratification and admixture. However, the length of a region found in association with a disease is usually very large because of linkage disequilibrium (LD). Here, we define a multimarker proportional TDT (mTDTP) designed to improve locus specificity in complex diseases that has good power compared to the most powerful multimarker TDTs. The test is a simple generalization of a multimarker TDT in which haplotype frequencies are used to weight the effect that each haplotype has on the whole measure. Two concepts underlie the features of the metric: the ‘common disease, common variant’ hypothesis and the decrease in LD with chromosomal distance. Because of this decrease, the frequency of haplotypes in strong LD with common disease variants decreases with increasing distance from the disease susceptibility locus. Thus, our haplotype proportional test has higher locus specificity than common multimarker TDTs that assume a uniform distribution of haplotype probabilities. Because of the common variant hypothesis, risk haplotypes at a given locus are relatively frequent and a metric that weights partial results for each haplotype by its frequency will be as powerful as the most powerful multimarker TDTs. Simulations and real data sets demonstrate that the test has good power compared with the best tests but has remarkably higher locus specificity, so that the association rate decreases at a higher rate with distance from a disease susceptibility or disease protective locus

Predictive modeling of groundwater nitrate pollution using Random Forest and multisource variables related to intrinsic and specific vulnerability: a case study in an agricultural setting (Southern Spain)

Watershed management decisions need robust methods, which allow an accurate predictive modeling of pollutant occurrences. Random Forest (RF) is a powerful machine learning data driven method that is rarely used in water resources studies, and thus has not been evaluated thoroughly in this field, when compared to more conventional pattern recognition techniques key advantages of RF include: its non-parametric nature; high predictive accuracy; and capability to determine variable importance. This last characteristic can be used to better understand the individual role and the combined effect of explanatory variables in both protecting and exposing groundwater from and to a pollutant.In this paper, the performance of the RF regression for predictive modeling of nitrate pollution is explored, based on intrinsic and specific vulnerability assessment of the Vega de Granada aquifer. The applicability of this new machine learning technique is demonstrated in an agriculture-dominated area where nitrate concentrations in groundwater can exceed the trigger value of 50 mg/L, at many locations. A comprehensive GIS database of twenty-four parameters related to intrinsic hydrogeologic proprieties, driving forces, remotely sensed variables and physical–chemical variables measured in “situ”, were used as inputs to build different predictive models of nitrate pollution. RF measures of importance were also used to define the most significant predictors of nitrate pollution in groundwater, allowing the establishment of the pollution sources (pressures).The potential of RF for generating a vulnerability map to nitrate pollution is assessed considering multiple criteria related to variations in the algorithm parameters and the accuracy of the maps. The performance of the RF is also evaluated in comparison to the logistic regression (LR) method using different efficiency measures to ensure their generalization ability. Prediction results show the ability of RF to build accurate models with strong predictive capabilitie