Fig. 1

Multi-omics (un)supervised analyses of lung neuroendocrine neoplasms. a Multi-omics factor analysis (MOFA) of transcriptomes and methylomes of LNEN samples (typical carcinoids, atypical carcinoids, and LCNEC). Point colours correspond to the histopathological types; coloured circles correspond to predictions of histopathological types by a machine learning (ML) algorithm (random forest classifier) outlined in b; filled coloured shapes represent the three molecular clusters identified by consensus clustering. The density of clinical variables that are significantly associated with a latent factor (ANOVA q-value < 0.05) are represented by kernel density plots next to each axis: histopathological type for latent factor 1, sex and histopathological type for latent factor 2. b Confusion matrix associated with the ML predictions represented on a. The different colours highlight the prediction groups considered in the survival analysis and the colours for machine learning are consistent between panel b and upper panel c. Black represents typical carcinoids predicted as typical, pink represents atypical carcinoids predicted as typical, red represents atypical carcinoids predicted as atypical, and blue represents LCNEC samples predicted as LCNEC. For the unclassified category, the most likely classes inferred from the ML algorithm are represented by coloured arcs (black for typical, red for atypical, blue for LCNEC, and light grey for discordant methylation-based and expression-based predictions). c Kaplan–Meier curves of overall survival of the different ML predictions groups (upper panel) and histopathological types (lower panel). Upper panel: colours of predicted groups match panel b. Lower panel: black-typical, red-atypical, blue-LCNEC. Next to each Kaplan–Meier plot, matrix layouts represent pairwise Wald tests between the reference group and the other groups, and the associated p-values; 0.01 ≤ p < 0.05, 0.001 ≤ p < 0.01, and p < 0.001 are annotated by one, two, and three stars, respectively. Data necessary to reproduce the figure are provided in Supplementary Data 1