Biological validation of computationally determined gene-gene interaction
Hang in there, this answer will grow over time.

Just off the top of my head, I think we could write a small book (or a very long review article) to cover both the depth and the breadth of your question(s).

First, we need to define, and/or clarify, some terms.  The term interaction probably means different things to different authors at different times.  In fact, one author may use this term to mean different things at different times.  So I would like to propose that we make some distinctions.  For example, I would make a distinction between a genetic interaction between two genes (which is typically detected in one of the model organisms, using a genetic test between two loss-of-function alleles) versus a protein-protein interaction (sometimes called a PPI) between the two proteins encoded by those same two genes.  PPIs have been detected classically by co-sedimentation in a sucrose density gradient, or co-immunoprecipitation (co-IP), or by affinity chromatography.  More recently PPIs have been detected by mass spectrometry (MS) (sometimes coupled with affinity chromatography).  PPIs have been inferred by using proxy assays, such as the yeast two hybrid (Y2H) assay.

PPIs can also be detected by surface plasmon resonance (SPR) assays, and there may well be others.

So, when you say gene-gene interactions, what precisely do you mean?