Fig. 2

Inferred protease activitity of MMP-9, ADAM8 and ADAM17 in CSF is increased in neoplastic meningitis. Catalytic efficiencies for FRET-based peptide substrates have been determined previously across a panel of purified recombinant enzymes [13]. Observed cleavage efficiencies for MMP-2, MMP-9, ADAM8 and ADAM17 for PEPDab Substrates 5, 8, 10, 13 and 14 (modified from [13] are shown a. Effects of broad-spectrum MMP-inhibitor batimastat (BB-94+) treatment on observed substrate cleavage in representative CSF samples. Combination of specific substrates and inhibitors allow to infer protease activities accurately (b). PrAMA inferred the cleavage signatures from (Fig. 1a), using parameters from (a). PrAMA inference results in CSF in patients with NM were compared to control individuals and patients with brain metastases w/o NM. The box indicates the interquartile range, blue bar indicates the median, red bar denote the mean values and whiskers indicate the 95% confidence interval. Open dots represent the individual samples (o), extreme values are marked with asterisks. Inferred differences were statistically significant for MMP-9, ADAM8 and ADAM17, stars indicate * p <0.01; ** p <0.005, *** p <0.001 (c)