Table 1.
Classifying HNSCC overall survival from TP53 mutation
| Classifier | HR (D vs. ND) | HR, 95% CI | P value | C | C, 95% CI | Predictions
|
|
|---|---|---|---|---|---|---|---|
| D, ND | D/(D + ND) | ||||||
| Poeta rules | 1.40 | 1.0–1.98 | 0.05 | 0.55 | 0.51–0.60 | 85, 139 | 0.38 |
| Poeta rules + Splice | 1.34 | 0.96–1.89 | 0.09 | 0.55 | 0.51–0.60 | 105, 119 | 0.47 |
| WAF1 ≤20 % | 1.28 | 0.77–2.14 | 0.34 | 0.54 | 0.51–0.58 | 189, 35 | 0.84 |
| WAF1 ≤10 % | 1.12 | 0.78–1.62 | 0.54 | 0.54 | 0.51–0.58 | 151, 73 | 0.67 |
| Density ≥0.5 | 1.09 | 0.75–1.60 | 0.65 | 0.54 | 0.51–0.58 | 160, 64 | 0.71 |
| PPH-2 possibly | 1.07 | 0.66–1.73 | 0.79 | 0.54 | 0.51–0.58 | 189, 35 | 0.84 |
| VEST ≥0.4 | 1.07 | 0.62–1.82 | 0.82 | 0.54 | 0.50–0.58 | 195, 39 | 0.87 |
| Distance ≤20 Å | 0.99 | 0.66–1.47 | 0.95 | 0.54 | 0.50–0.58 | 169, 55 | 0.75 |
| PPH-2 Probably | 0.98 | 0.66–1.43 | 0.90 | 0.54 | 0.51–0.58 | 164, 60 | 0.73 |
| Distance ≤10 Å | 0.89 | 0.63–1.25 | 0.49 | 0.55 | 0.51–0.59 | 121, 103 | 0.54 |
| VEST ≥0.8 | 0.86 | 0.57–1.29 | 0.47 | 0.55 | 0.50–0.59 | 177, 47 | 0.79 |
| AGVGD C35 | 0.84 | 0.59–1.20 | 0.34 | 0.55 | 0.51–0.59 | 145, 79 | 0.65 |
| SIFT | 0.84 | 0.53–1.33 | 0.45 | 0.55 | 0.50–0.59 | 189, 35 | 0.84 |
| AGVGD C45 | 0.79 | 0.56–1.11 | 0.18 | 0.55 | 0.51–0.59 | 130, 94 | 0.58 |
| POSE | 0.75 | 0.50–1.12 | 0.16 | 0.55 | 0.51–0.59 | 174, 50 | 0.78 |
Performance achieved by 15 different classifiers for predicting overall survival in HNSCC patients from TP53 mutation. Classifiers include: the rules devised by Poeta et al. with or without splice-site considerations (Poeta rules + Splice and Poeta rules, respectively); site-specific clustering density ≥0.05 (Density ≥0.5); WAF1 transactivation as a percent of wild type (WAF1 ≤20 % and WAF1 ≤10 %); site of mutation—DNA distance at two discrete cutoffs (Distance ≤20 Å and Distance ≤10 Å); PolyPhen-2, with two different dichotomizations of the tripartite output (PPH-2 Possibly and PPH-2 Probably); the VEST algorithm with two different thresholds (VEST ≥0.8 and VEST ≥0.4); Align-GVGD, with two different dichotomizations of the septpartite output (AGVGD C45 and AGVGD C35); and the SIFT and POSE algorithms each with a single implementation
C is the concordance statistic, CI is the confidence interval, HR is the hazard ratio calculated for disruptive (D) vs. non-disruptive (ND) classifications, and Predictions shows the relative classification (D vs. ND) for the 230 TP53 variants, for each classifier
See “Materials and methods” for a complete description of each classifier and performance statistic