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You should have at least the following two attributes in the Metadata, treatment (including two subgroups) and subject ID (to pair the two samples). When performing differential analysis, choose ANOVA and include both attributes into the ANOVA model, the two-way ANOVA is mathematically equivalent to paired t-Test.

Can I compare one attribute at a time versus all of the others combined?

Yes, you can use the Compute biomarkers task which will perform Student's t-Tests on the selected attribute, by comparing one subgroup at a time to all of the others combined; by default, the up-regulated features (e.g. genes) are reported as biomarkers. An alternative option is to set up the differential analysis model comparison is this way; for more information please see the information here for each model. 

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