Mean difference analysis for a paired data with zero inflation. Can Wilcoxon test work? I have a set of data that represent the sum of white matter streamlines termination in 64 regions of interest in the brain surface collected from 40 subjects.
Below is an example of a paired data of one region for both right and left brain hemispheres. The variable "value" represents the sum of all streamlines that terminated within this region.
side <- c("Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Right","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left","Left")

value <- c(0,0,0,306,4,156,2,3,0,146,0,218,0,0,74,5,0,833,0,640,76,49,0,0,163,65,0,0,5,14,2,0,92,229,0,23,338,0,0,11,90,51,0,4,394,50,138,0,12,481,325,237,0,574,102,391,2,104,559,0,348,427,554,214,786,312,407,45,356,114,19,104,194,833,192,354,126,4,716,129)

data <- data.frame(side, value)

head(data)

   side value
1 Right     0
2 Right     0
3 Right     0
4 Right   306
5 Right     4
6 Right   156

As can be seen, several subjects ended with zero value, especially on the right side.
When looking into the distribution of the data as below, the right side data is highly skewed due to zero inflation.
ggplot(data, aes(x = value, color = side)) + 
  geom_histogram(aes(y=..density..), colour="black", fill="white") + 
                   geom_density(alpha=.2, fill="#FF6666")


These zero values are true zeros and have to be included in my analysis. It is normal for the brain areas to have zero values of certain white matter streamlines.
My purpose is to test the mean difference and to bring a parameter estimate or an effect size measurement to plot for visualization. My null hypothesis is that there is no significant difference between the two sides. Can the Wilcoxon signed-rank test still be used with such data? I am using R but can use SPSS if required.

In relation to the title question I think that it's okay, at least under some conditions. I would be inclined to omit the observations that are the difference of two 0's as contributing no information about the difference rather than simply apply an adjustment of ties. (In any case, certainly we cannot just enter them all as if we were dealing with continuous comparisons.)
However, if you're interested in a mean difference, I would not at first glance suggest a signed rank test since it also does not correspond to the hypothesis about population means without additional assumptions.
There are several potential alternatives for testing means. Here are some:

*

*A plain permutation test of means.


*Come up with a suitable parametric model and then derive a good test for comparing means; ideally with some knowledge of the likely behavior of the quantities. (In this case I don't have enough domain knowledge to say much of anything but it seems that the non-zero measurements are on the positive half-line and perhaps a zero-inflated gamma might be adequate.)


*Start with the exercise in 2. to arrive at a hopefully plausible model, but rather than rely on it being quite correct, use it as the basis of a permutation test. This may require additional assumptions to make it a suitable test of means if the model is not quite right.


*Use a bootstrap test.


*After checking that the type I error rate is not going to be too far off with n=40, on distributions that looks something like the one at hand, simply use a paired t-test.
Even when the significance level is fine, this may result in some loss of power relative to a more suitable model (there's not much tendency for relative efficiency to improve with sample size). This may or may not be a major issue, depending on circumstances.


*Make the additional assumptions necessary to use a signed rank test (or indeed any other test, such as a robust test) to compare population means, and adjust the approach to deal with the issue with the differences of two 0s.
