Should all samples from exactly the same protocol have similar number of reads (raw data)?

Depending on how you’re analyzing your data, @fgara, you may already be doing this. For example, if you run qiime diversity core-metrics, you pass an integer to --p-sampling-depth that describes the sample depth to which you would like to randomly sample, and which drops samples with insufficient depth. Other plugins do things differently.

Sample normalization has been widely discussed both on this forum, and in the larger bioinformatics community. This topic will give you a brief intro to how QIIME 2 generally handles normalization (i.e. plugins/methods usually implement their own normalization procedures), and many resources to explore if you want to learn more about the topic.

Happy hunting!
Chris :egg: