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Source: Campillos et al (2008). Drug Target Identification Using Side-Effect Similarity. Science 321:263-266.

Living organisms are highly complex systems and when a foreign molecule is introduced (i.e. injected) into the body, non-specific bindings may occur that result in unwanted (and sometimes harmful) side-effects. Target prediction is usually done through structural similarities; where similar compounds affect identical targets. However, two completely different molecules may also share targets which is overlooked in this classic method. The authors of this paper combine the strength of structure-based similarities with symptoms-based knowledge to draw more conclusive predictions. They start with ~700 drugs and extract their reported side-effects. They remove the inherent redundancy (e.g. vomiting and nausea largely overlap) and also normalize the probability of sharing a target based on the total number of occurrences (e.g. dizziness is quite common but other side-effect are more specific).

Following their prediction step, they also validate 20 predicted drugs with significant probabilities of sharing a target (note that all of these drugs are selected so that they represent different classes of drugs with varying therapeutic purposes). They succeed in validating 13/20 of these cases using in vitro and in vivo experiments which is quite impressive.