Fig. 1: Discovery of CSEs as immunotherapy targets in pediatric solid and brain tumors.
From: Discovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression
A Schematic illustration of the concept of exploiting CSEs, which include both gene-level and alternatively spliced exons as targets for immunotherapy (in part created with BioRender software). B Pediatric solid (n = 840) and brain (n = 692) tumor RNA-seq data sets used for discovery. The sample count in each tumor type is colored by the data source (i.e., PCGP, TARGET, and St. Jude’s ClinGen). Nine major types of solid tumors are marked by their abbreviations as follows: adrenocortical carcinoma (ACC, n = 22), desmoplastic round cell tumor (DSRCT, n = 9), Ewing sarcoma (EWS, n = 20), melanoma (MEL, n = 31), neuroblastoma (NBL, n = 219), osteosarcoma (OS, n = 136), retinoblastoma (RB, n = 23), rhabdomyosarcoma (RMS, n = 86), and Wilms tumor (WT, n = 158). Rare solid tumors are binned into the category of other solid tumors (other ST, n = 136). Five brain tumor types are shown by their abbreviation as follows: choroid plexus carcinoma (CPC, n = 21), ependymoma (EPN, n = 139), high-grade glioma (HGG, n = 155), low-grade glioma (LGG, n = 140), medulloblastoma (MB, n = 126). Rare brain tumors are binned into other brain tumors (other BT, n = 111). C Analysis workflow (top) and resulting data (bottom) involving the following steps: (1) Quantify exon-level expression by RNA-seq mapping; (2) Select exons highly expressed in tumor but not normal tissues; (3) Retain exons from surfaceome/matrisome; (4) Perform curation expression specificity to remove artifacts and to categorize Tier 1 and Tier 2 candidates representing those without and with expression in adjacent/critical tissues (e.g., brain, liver, bone marrow); Tier 1 targets also require to have low proteomics expression in GTEx. (5) Classify targets into AS exons versus gene-level.
