EHdn supports case-control and outlier analyses of the underlying dataset. The case-control analysis is based on a one-sided Wilcoxon rank-sum test. It is appropriate for situations where a significant subset of cases is expected to contain expansions of the same repeat.
The outlier analysis is appropriate for heterogeneous cohorts where enrichment for any specific expansion is not expected. The outlier analysis bootstraps the sampling distribution of the 95% quantile and then calculates the z-scores for cases that exceed the mean of this distribution. The z-scores are used for ranking the repeat regions. Similar outlier-detection frameworks were also developed for exSTRa [23 (link)] and STRetch [25 (link)].
Both the case-control and the outlier analyses can be applied either to the counts of anchored IRRs or to the counts of paired IRRs. We refer to these as locus or motif methods, respectively. The high-ranking regions flagged by the analysis of anchored IRRs correspond to approximate locations of putative repeat expansions. The high-ranking motifs flagged by the analysis of paired IRRs correspond to the overall enrichment for repeats with that motif.
The outlier analysis is appropriate for heterogeneous cohorts where enrichment for any specific expansion is not expected. The outlier analysis bootstraps the sampling distribution of the 95% quantile and then calculates the z-scores for cases that exceed the mean of this distribution. The z-scores are used for ranking the repeat regions. Similar outlier-detection frameworks were also developed for exSTRa [23 (link)] and STRetch [25 (link)].
Both the case-control and the outlier analyses can be applied either to the counts of anchored IRRs or to the counts of paired IRRs. We refer to these as locus or motif methods, respectively. The high-ranking regions flagged by the analysis of anchored IRRs correspond to approximate locations of putative repeat expansions. The high-ranking motifs flagged by the analysis of paired IRRs correspond to the overall enrichment for repeats with that motif.
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