Nucleic Acids Research, 2009, Vol. 37, No. 3 775 Figure 1. Perturbations extracted from genes involved in the Diabetes Mellitus Type II pathway in the Kyoto Encyclopedia of Genes and Genomes (21). Diﬀerences in perturbation direction are large for some members of the pathway, note that the scale bar is logarithmic. The phenotypes in this study were selected based on prevalence in the literature without regard to their use in vivo or in vitro. For instance, in diabetes a change in blood glucose levels signals a change in disease state— clearly a phenotype monitored following perturbation in vivo. Likewise, in cancer a change in the number of metastases is exclusively described in in vivo systems. In contrast, insulin sensitivity can be used to describe both in vivo and in vitro systems. For cancer, cell proliferation and apoptosis rates are also described both in vivo and in vitro. If our hypothesis that perturbed genes and proteins form the underpinnings of disease mechanisms, these enti- ties should be well represented in pathway diagrams and among drug candidates. We applied our trained algo- rithm to a set of 14 345 sentence–relationship facts for genes from our analysis corpus belonging to a diabetes pathway (Figure 1). Predictably, our algorithm found a strong correlation between the number of Medline abstracts in which a gene is mentioned and the number of times it is described as perturbed (r2 = 0.70). The results in Figure 1 show the diﬀerence in intensity and modality in which each gene is described or pursued experimentally. Some genes were typically more increased or decreased, often reﬂecting their roles in therapeutics. Examples of signiﬁcantly (P < 10 6) increased were insu- lin, interleukin 2 or parathyroid hormone. Among the decreased were such genes as epidermal growth factor receptor; caspase 8 and plasminogen activator, urokinase receptor. We compared detected perturbation counts from the analysis corpus against the gene–disease associations included in the OMIM Morbid Map (OMIM online refer- ence, http://www.ncbi.nlm.nih.gov/omim/). The average