ATCC 33277             Increased Decreased cancer metabolism inhibitor unchanged Not detected Total W83   396 248 622   1266 Increased 380 242 10 124 4   Decreased 235 5 140 79 11   Unchanged 570 93 75 345 57   Not detected   56 23 74     Total 1185           The numbers of proteins showing increased, decreased or unchanged abundance in the internalized state for each analysis are given. Entries indicate the number of proteins from each category in one analysis that are assigned to the categories in the other analysis, including proteins that are

not detected in a specific analysis. Whole cell proteomics measurements of this type are noisy and the trade off between quantitative selleck chemicals llc FDR (false discovery rate) and FNR (false negative rate) is made based on the informed judgment of the analyst, and often tends to be ad hoc and arbitrary in practice [9, 14]. The q-value cut-off of 0.01 used here for statistical significance selleck chemical based on formal hypothesis testing was in good agreement with experimentally derived error distributions, as illustrated by the two pseudo M/A plots given in Additional

file 1. The present findings serve to show the value of examining trends in groups of proteins, both as an end in itself with respect to biological questions and as feedback STK38 in the determination of proper cut-off values for the quantitative significance testing of individual proteins. As proteomics technology improves and it becomes economically feasible to run a greater number of independent cultures (biological replicates) than what was possible here, the

overall noise issue in any one set of measurements will be less of a concern, and it will be easier to distinguish biological noise from deficiencies with respect to analytical repeatability, and thus identify biological trends that are truly significant rather than stochastically driven. Nonetheless, as in our previous work [9] the trends identified here are consistent with what we know about the behavior of the organism under intracellular conditions [3, 9, 16]. Comparison between W83 and ATCC 33277 annotations for proteomics As expected, the new analysis identified more proteins, 1266 proteins compared to 1185 in the previous analysis (Table 1). The number of proteins with statistically significant changes between internalized and medium incubated cells also increased, from 380 proteins with increased abundance to 396 proteins and from 235 proteins with decreased abundance to 248 proteins. This was a consequence of the higher number of proteolytic fragments detected across the proteome.