Background. In the past years devicing methods for discovering gene regulatory mechanisms at a genome-wide level has become a fundamental topic in the field of system biology. The aim is to infer gene-gene interactions in a more sophisticated and reliable way through the continuously improvement of reverse engineering algorithms exploiting microarray technologies. Motivation. This work is inspired by the several studies suggesting that co-expression is mostly related to "static" stable binding relationships, like belonging to the same protein complex, rather than other types of interactions more of a "causal" and transient nature (metabolic pathway or transcription factor-binding site interaction). Discerning static relationships from causal ones on the basis of their characteristic regulatory structures and in particular identifing "dense modules" with protein complex, and "sparse modules" with causal interactions such as those between transcription factor and corresponding binding site, the performances of different network inference algorithms in artificial and real networks (derived from E.coli and S.cerevisiae) can be tested and compared. Results. Our study shows that methods that try to prune indirect interactions from the inferred gene networks may fail to retrieve genes co-participating in a protein complex. On the other hand they are more robust in the identification of transcription factor-binding sites dependences when multiple transcription factors regulate the expression of the same gene. In the end we confirm the stronger co-expression regarding genes belonging to a protein complex than transcription factor-binding site, according, also, to the effect of multiple transcription factors and a low expression variance.