Figure 5.
Excerpted results from five example analyses
(A) Visualization. GPSEA generates a cartoon showing the location and frequency of variants in protein sequences. The following panels show examples of statistically significant GPCs identified by GPSEA.
(B) Categorical analysis. Several phenotypic abnormalities (HPO terms) such as neurofibromas, optic nerve glioma, and Lisch nodules are significantly less frequent in individuals with neurofibromatosis type 1 due to variants located at the arginine residue at position 1,830 of neurofibromin isoform 1 than in those with different mutations (FET, IF-HPO, Benjamini-Hochberg correction).
(C) Severity score. A boxplot with counts of abnormalities in five organ systems in the individuals with mutations in RERE showing the association of the mutations in the Atrophin domain with abnormalities in multiple organ systems27 (Mann-Whitney U test, p = 1.44 × 10−3). The boxes represent the Q1–Q3 range, and the whiskers extend to the farthest score lying within 1.5× the interquartile range. The blue line denotes the median score.
(D) de Vries score. Boxplots representing the association of the de Vries phenotype score13 and missense variants in CHD8 (Mann-Whitney U test, p = 8.99 × 10−4).
(E) Continuous phenotypes. Association of CYP21A2 genotype (homozygous missense vs. other) with concentration of 17-OH progesterone (t test, p = 7.91 × 10−6).
(F) Survival analysis. Comparison of the onset of Stage 5 chronic kidney disease (HP:0003774) in individuals with UMOD mutations showing a significantly earlier onset of the disease in the individuals with NM_003361.4:c.744C>G; p.(Cys248Trp) than in those with NM_003361.4:c.947A>C; p.(Gln316Pro) (log-rank test, p = 4.1 × 10-4). Missense∁, set complement of “missense,” i.e., any mutation that is not missense; LoF, loss of function.