Pathway curation methods can also impact analyses. Most databases rely on expert review for pathway curation; however, users of these databases should be aware of their update intervals and criteria used as evidence for inclusion in pathways. Alternatively, electronic curation employs text-searching algorithms to infer functional relationships. While these inferred annotations can be useful for hypothesis generation, their accuracy is unreliable [18], making them unsuited to many pathway analyses. Finally, targeted manual curation can be particularly appropriate when an investigator has expertise in a biological realm that is poorly annotated in databases. While potentially time-consuming, manual curation can synthesize recent results with established relationships to produce novel candidate pathways [19, 20] or gene sets representing positive controls for pathway analysis [21].
