Figure 3.

Definition of the z-score with regard to the set of functional TMs. Figure 3A shows the normalized sequence complexity/hydrophobicity measures of the membrane anchors (in blue), functional TM-helices (UniProt-derived; in red) and functional α-helices (in green). The univariate z-score is given by the squared sums of two normalized measures. The expectation of the z-scores for the functional TM-helices set is zero. The regression line (ρ = -0.436) for the functional TM set and its normal are indicated. The negative halve of the functional TM helices' z-scores is given by the inequality (3) while z-scores failing to satisfy the inequality makes up the positive halve. It is apparent that the majority of the membrane anchors have negative z-scores while the functional α-helices have positive z-scores. Figure 3B depicts the distributions of the membrane anchors (in blue) as simple TM helices and the functional TM-helices (in red) as complex TM helices. For illustrative purpose, the membrane anchors are approximated by the Gumbel distribution given its long left tail while the functional TM-helices are fitted to the normal distribution. For a given z-score threshold, the complex TM helices are partitioned into true-positives (TP) and false-negatives (FN) while the simple helices are divided into the true negatives (TN) and false-positives (FP). Consequently, the false-positive and false-negative rates can be determined for a given z-score threshold defined by equation (4).