This is highly signifi cant and can be quantified with a simple Fisher exact test. Explicitly, the probability p of 20 or more resistant samples in the top 25 correlations is less than 9 10 7. The K S significance score selleck catalog can be calculated by counting the number of times a random rearrangement of the samples gives a better enrichment, we find p 3 10 6. The enrichment plot is given in Figure 4A. As expected the top scoring correlations were dominated by samples from blood derived cells, for simplicity we restricted our analysis to the top 100 most significantly correlating sam ples. However, two studies in unrelated tissue pathologies were highly correlated with the corticosteroid resistant profile. These were a comparison of lung epithelia with cancer in smokers and a differential expression between healthy and cancerous pancreatic tissue.

The smoking study consisted of non diseased lung epithelia from 187 individual smokers 97 of whom were diagnosed with lung cancer. Ranking the samples accord ing to query correlation score we find that in the top 97 there are 64 cancer cases and in the bottom 90 there are 57 non cancer cases, with a significance score of p 5 10 5. The K S significance is p 2 10 4. The enrichment for positive correlations with the corticosteroid resistance profile in the cancer cases is shown in Figure 4B. Interest ingly, it has been shown that there is a down regulation of the glucocorticoid receptor in small cell lung cancer and reversing this promotes cancer cell apoptosis.

The pancreatic cancer study sought to establish a transcriptional signature of tumour versus normal pan creatic tissue by laser capture of cancerous and normal tis sue from the same pancreas. In total 39 sample pairs were published and we find a high positive correlation with the corticosteroid resistance profile, p 2 10 6 and a K S significance score of p 3 10 7. The enrichment curve is shown in Figure 4C. In this context it has been reported that loss of GR Carfilzomib expression has been seen in pancreatic car cinoma relative to normal tissue and elevating GR expression has been shown to inhibit pancreatic tumour growth in a hamster model. The query results are given in the additional file 2. Neurodegenerative Disease The analysis of gene expression changes associated with neurodegenerative disease has been hampered by the difficulty of extracting high quality RNA from post mor tem tissue. One way of validating a disease asso ciated gene expression profile is to show that it shares significant features with profiles derived from indepen dent experiments on related pathologies. A positive result would validate the query profile and furthermore lead to a more robust core response profile based on multiple experiments.