More Than 1,001 Problems with Protein Domain Databases: Transmembrane Regions, Signal Peptides and the Issue of Sequence Homology
Figure 6
Relationship between the gathering score and the corresponding E-value threshold for Pfam domain library release 23.
Whereas the y-axis shows the gathering score threshold (GA) for the global-mode search, x-axis shows the corresponding E-value threshold (in decimal log scale) calculated with the domain-specific extreme-value function with parameters provided in the corresponding HMM file (for an NR database size of 7365651 sequences) for this score. The upper plot represents the distribution for 9126 domains without detected SP/TM region, the middle part shows the same for the 1214 domains with SP/TM problems. Effectively, there is no clear correlation between gathering score and E-value threshold. If E-values close to 0.1 are considered significant, all dots should be close to the “−1” line (horizontal dashed lines) in this graph and, indeed, there is some agglomeration of data points in that area; yet, there are numerous outliers. Note that the E-values are computed using the equationwhere
is the database size,
and
are the extreme value distribution (EVD) parameters of the domain model. The bottom plot depicts the histogram of the 10340 domains in Pfam rel.23. The median of all log E-values that corresponded to the domain-specific GAs is found to be −1.16. This translates to an E-value of 0.07.