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We carried out a number of some experiments and got 10 independent 2-samples datasets.

Is it possible to show a significant difference between the two samples, if each of them contains more than 75% zeros (and we don't want to exclude zeros from these samples)?

Example of sample's box plots obtained by one of our experiments below:

two samples

It is important to note that in 10 independent models (experiments) the difference is approximately the same visually, but Kolmogorov-Smirnov, Brunner-Munzel and Wilcoxon tests show unstable p-values for different models.

What statistical test should we use to show the significance of differences in these cases? Or zero-values filtering is necessary?

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    $\begingroup$ What do you refer to with "significant difference between the two samples"? Significantly different mean? Or do you want to a more general check testing if both samples come from the same distribution? $\endgroup$ – David Mar 26 at 12:39
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With a lot of zeros in both series, it may be difficult to reject that the null that the means are the same. But you could test for differences in the deciles (or other quantiles) from the two distributions. If the tails are different then the samples are different. For a test see Li, Tiwari and Wells (1996).

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Questions: 1. Is your outcome/dependent variable a count data? If so, then you need to see if the zero inflation is actually an inflation in comparison to the conditional mean. If there isn't zero-inflation, then you can try poisson or negative binomial model. If there is zero-inflation, you can try zero-inflated or hurdle poisson (negative binomial) models. 2. What is your exact research question? 3. What's your sample size?

Try plotting a conditional barchart to get a better picture of your data.

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I think the supremum should be quite different even when we include 0s and hence K-S stat should be significant. Can you please elaborate, what you mean when you say $p$ values are unstable? Do you mean, they differ vastly across the 10 experiments? Can you share empirical cdf plots?

Also, have you tried ANOVA? It should be able to show that these distributions have different means.

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