Fig. 2: Using SnapMine to investigate cryptic exons in GTEx and SRA data compilations.
From: Large-scale RNA-Seq mining reveals ciclopirox olamine induces TDP-43 cryptic exons
a, b Average percent spliced-in (PSI) of cryptic exons (CEs) in AGRN, ATG4B, G3BP1, HDGFL2, MYO18A, PFKP, RANBP1, STMN2, UNC13A, and UNC13B. Data are presented as box plots with median and interquartile range, along with whiskers from minimum to maximum values. Each point represents a sample in Genotype-Tissue Expression (GTEx) project dataset (n = 19803) (a) All samples. Average PSI is not always 0 and the CE in UNC13B has particularly high inclusion rates. b Tissue-specific expression indicates CE inclusion differs by tissue. Some cryptic exons have generally low inclusion in all samples while others have tissue-specific enrichment. Points are colored in a gradient from blue (PSI = 0%) to red (PSI ≥ 20%). The following tissues are sampled: adipose (n = 28446), adrenal gland (n = 6028), bladder (n = 462), blood (n = 23056), blood vessel (n = 30756), bone marrow (n = 4488), brain (n = 64482), breast (n = 10604), cervix uteri (n = 418), colon (n = 18084), esophagus (n = 34694), fallopian tube (n = 198), heart (n = 20724), kidney (n = 2156), liver (n = 5522), lung (n = 14410), muscle (n = 19382), nerve (n = 14498), ovary (n = 4290), pancreas (n = 7920), pituitary (n = 6622), prostate (n = 5786), salivary gland (n = 3916), skin (n = 42680), small intestine (n = 4246), spleen (n = 5610) stomach (n = 8448), testis (n = 9020), thyroid (n = 15532), uterus (n = 3498), vagina (n = 3806). c Heatmap representation of percentage GTEx samples positive for each cryptic exon in each tissue. Samples are considered positive if avgPSI > 5% for the cryptic exon. ARHGAP32, PFKP, RANBP1, and UNC13B have tissue-specific enrichment. A gradient from white (% positive = 0%) to deep red (% positive ≥ 20%) is used to color the tiles. d UCSC Genome Browser visualization of the STMN2 cryptic exon in untreated neuroblastoma cell lines. Blue arrow indicates the cryptic exon. e UCSC Genome Browser visualization of HDGFL2, PFKP, and TRRAP cryptic exons in MDA-MD-231 cells after TDP-43 and/or SRSF3 knockdown. Blue arrow indicates the cryptic exon. Lanes with red-colored reads indicate a TDP-43 knockdown. Lanes with black-colored reads represent samples without TDP-43 knockdown. The PSI of HDGFL2, PFKP, and TRRAP cryptic exons appears to increase with co-knockdown of SRSF3 compared to a TDP-43 only knockdown. SRSF3 knockdown appears sufficient in these cells for cryptic exon inclusion.
