Unsupervised clustering, network and gene enrichment analysis for available RNA-seq data identify PanNET subgroups associated with hypoxia and metabolic reprogramming. a, Unsupervised clustering identified three distinct PanNET subgroups (1–3). b, A gene signature defining three expression groups previously described in PanNETs showed enrichment of expression of the intermediate-group genes43 in Group 1 and the metastasis-like PanNET (MLP) genes43 in Group 3. c, Network analysis identified a significant sub-network of genes differentially expressed between Group 3 and other groups (Group 1 and Group 2). Red nodes represent genes upregulated in Group 3 and green nodes represent genes upregulated in other groups. Shaded areas represent network communities. d, Gene enrichment analysis for genes belonging to the sub-network shown in b. e, Heatmap showing the differential expression of genes belong to the identified sub-network. Somatic mutations in some of the recurrently mutated genes are shown (MEN1, DAXX, ATRX and members of the mTOR pathway: DEPDC5, MTOR, PTEN, TSC1 and TSC2).