Figure 6

Effects on the homology searches for TCDB with the removal of simple and complex TM helices. The performance of the homology searches for 2202 TCDB entries between their original and masked sequences are shown for the z-score thresholds of f = 0.840, 1.000, 1.282, 1.645 and 1.980 respectively. The corresponding false-negative rates are 20%, 16%, 10%, 5% and 2.5% respectively. Figure 6A shows the masked ratios (m = number of masked TMs over total TMs) of the 2202 TCDB entries. The median mask ratios of the TCDB entries are 0.41, 0.33, 0.18, 0.08 and 0.00 for f = 0.840, f = 1.000, f = 1.282, f = 1.645 and f = 1.980 respectively. The non-zero mask ratio means that some TM helices in the multi-spanning entries are considered simple. The corresponding total number of entries (where 0 < m < 1) are 1747, 1705, 1533, 1071 and 680 respectively. On average, each masked TCDB entry has about 9 to 10 TM helices. Therefore, most TCDB entries are multi-spanning. Figure 6B shows that the false-discovery rates of the searches for the masked sequences are at least equal or less than that of their corresponding full sequences at a comparable sensitivity. This means that the masking of simple TMs can improve the false-discovery rates of the searches. This trend is independent of the different z-score thresholds that influence the level of masking (most masking at false-negative rate of 20% and least masking at false-negative rate of 2.5%). Figures 6C and 6D show the sensitivity plots of the searches for the 2202 TCDB sequences. The red, blue and black lines represent the sensitivities of the original, masked and control sequences respectively. The sensitivity of the original (red) and masked (blue) sequences are comparable at 1.0 for most of the sequences. At a sensitivity of 1, the number of false-negatives is zero. On the other hand, the sensitivity of the search for the control sequences (where the complex TMs are masked) deviates greatly from the sensitivity of 1. This implies that the masking of complex TMs has a detrimental effect on the TCDB classification.