How to compare .psi.gz files from two groups (or more than two samples) with different amount of samples in each condition.

[itszhengan]

Hi, First I want to know the meaning of "Total Reads" in .psi.gz files. And what kind of analysis can we use this data to do? Second, I want to compare .psi.gz files from two groups such as disease and normal, each with different number of samples. For example, I have 100 .psi.gz files from disease samples without replicates and 25 .psi.gz files from healthy samples. How do I perform differential analysis on this two group? If not, can we use other R or statistical methods to do this? Thank you.