This collective diversity of features is a major factor in explaining why different databases can yield divergent results from the same input data [22]. As such, an early discussion of pathway analysis recommended the use of multiple databases for each analysis [23]. This approach can balance the relative characteristics of each database used and can yield a measure of validation when different databases yield similar results. However, this strategy is most effective when it is supplemented by a systematic review of the results. Alternatively, further analyses can reveal broader findings that drive association signals across multiple smaller pathways: for example, one study analyzed pathway sets obtained through hierarchical clustering and identified an association between the canonical RAS/RAF/MAPK signaling pathway and breast cancer [4].
