RNA-Seq in SS identities dysregulated cancer pathways and SC-associated IncRNAs. (A) Heat map of differentially expressed protein-coding genes. The expression of 2989 genes changed significantly in SC compared to patient-matched control cells (P < .05). Of these, 525 were commonly up-regulated and 519 were commonly down-regulated. (B) Significantly dysregulated pathways in SS. Canonical pathway analysis was performed with IPA using genes that changed significantly in all 3 patients. The significance of the association between this dataset and the canonical pathway shown was measured by Fisher's exact test. (C) Gene set enrichment analysis. GSEA plots depict concordance between significantly changed genes in SS and the molecular mechanisms of cancer canonical pathway from IPA (left), phosphatidylinositol signaling pathway (middle), and TGFβ signaling (right). NES, normalized enrichment score; FDR q-val, false discovery rate q-value (the probability that a gene set with a given NES represents a false-positive finding). (D) Heat map of differentially expressed IncRNAs. 35 were commonly up-regulated and 50 were commonly down-regulated. (E) Graphical representation of the bioinfomatic filters used to identify SC-associated IncRNAs. Expressed RefSeq transcripts annotated as noncoding were compiled with non-redundant, noncoding Gencode transcripts to assemble a merged SS noncoding transcriptome and the filters noted were applied. (F) Genomic locus of AL513543.1, a noncoding transcript that is down-regulated in the SC of all 3 patients. Histograms have been normalized to account for differences in the number of reads per library. (G) Relative expression of 21 SC-associated IncRNAs across RNA-Seq human tissue datasets normalized to average RPKM in polyclonal CD4⁺ T-cells. Gray boxes indicate no detectable expression. Name color indicates directionality of expression change in SC (red = increased, blue = decreased).