Fig. 4

Pathways relevant to human health, development, and reproductive function are affected by dark and camouflaged genes. We characterized the pathways for dark and camouflaged genes using Metascape.org, including only genes where at least 5% of the CDS regions were dark (565 unique gene symbols; based on standard Illumina 100 nucleotide read lengths). a Specific pathway groups included Ub-specific processing proteases (R-HSA-5689880; logP = − 10.70), defensins (R-HSA-1461973; logP = − 9.43), ncRNA 3′-end processing (GO:0043628; logP = − 8.87), gonadal mesoderm development (GO:0007506; logP = − 8.76), spermatogenesis (GO:0007283; logP = − 8.29), spindle assembly (GO:0051225; logP = − 7.56), NLS-bearing protein import into nucleus (GO:0006607; logP = − 6.63), methylation-dependent chromatin silencing (GO:0006346; logP = − 4.98), activation of GTPase activity (GO:0090630; logP = − 4.67), and others. b Looking specifically at known protein-protein interactions, we found 103 proteins with 172 known interactions (Additional file 1: Figure S3) and, within those, identified four groups enriched for protein-protein interactions using the MCODE algorithm [28] (Fig. 4b). All four MCODE groups combined are primarily associated with RNA transport (hsa030313; logP = − 18.59; Additional file 1: Figure S4; accessed March 2019). Individually, the first group (MCODE1) is enriched for proteins involved in systemic lupus erythematosus (hsa05322; logP = − 6.55), cellular response to stress (R-HSA-2262752; logP = − 6.13), and RNA transport (hsa03013; logP = − 4.26; Additional file 1: Figure S5). The second group (MCODE2) is enriched with proteins involved in NLS-bearing protein import into nucleus (GO:0006607; logP = − 18.44; Additional file 1: Figure S6). The third and fourth groups do not have significant enrichment associations, likely because little is known about them; five of the six genes (PRR20C, PRR20D, PRR20E, SMN1, and SMN2) are completely or nearly 100% camouflaged, and several do not even have known expression measurements in GTEx [29] (Additional file 1: Figures S7-S9)