Comparative analysis revealed dosage sensitivity and regulatory patterns of lncrna in prostate cancer

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1 Electronic Supplementary Material (ESI) for Molecular BioSystems. This journal is The Royal Society of Chemistry 2016 Comparative analysis revealed dosage sensitivity and regulatory patterns of lncrna in prostate cancer Yongjing Liu, Rui Zhang, Ning Zhao, Qiang Zhang, Zichuang Yan, Yuanshuai Zhou, Zhiqiang Chang and Yan Xu* College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 10081, China These authors contributed equally to this work *Corresponding author

2 Supplementary Figure 1 The dosage effect score distributions. The two panels are the DES score distributions of PCGs and lncrnas in prostate cancer. The distribution plot is consistent with Samur et al. s study.

3 Supplementary Figure 2 The difference of DES between PCGs and lncrnas at different genomic locations.

4 Supplementary Table S1 GO terms enriched by PCGs with high dosage sensitivity Category Term Count P-Value GO: ~protein catabolic process E-03 GO:000907~macromolecule catabolic process 1 1.7E-03 GO:001603~proteolysis involved in cellular protein catabolic process E-03 GO:004427~cellular protein catabolic process E-03 GO:004426~cellular macromolecule catabolic process E-03 GO:000716~homophilic cell adhesion E-03 GO: ~insulin receptor signaling pathway E-03 GO: ~enzyme linked receptor protein signaling pathway E-03 GO: ~modification-dependent protein catabolic process 38.98E-03 GO: ~modification-dependent macromolecule catabolic process 38.98E-03 GO: ~cell junction assembly 7 6.7E-03 GO: ~protein localization 3 7.4E-03 GO:00334~cellular response to stress E-03 GO: ~cell junction organization E-03 GO: ~cellular response to UV E-03 GO:004898~embryonic morphogenesis E-02 GO: ~gastrulation with mouth forming second 1.03E-02 GO: ~cell cycle E-02 GO: ~smooth muscle contraction E-02 GO: ~transforming growth factor beta receptor signaling pathway E-02 GO:001626~death E-02 GO:000611~ubiquitin-dependent protein catabolic process E-02 GO: ~cellular protein localization E-02 GO: ~lipid localization E-02 GO: ~cellular macromolecule localization E-02 GO: ~NLS-bearing substrate import into nucleus 4 1.2E-02 GO: ~intracellular transport E-02 GO: ~cell death E-02 GO: ~membrane organization E-02 GO: ~lipid transport E-02 GO: ~tissue morphogenesis E-02 GO:006062~epithelial tube morphogenesis 8 2.1E-02 GO: ~histone H3 acetylation 2.18E-02 GO:00329~tube development E-02 GO:00219~central nervous system neuron axonogenesis E-02 GO: ~cellular response to insulin stimulus E-02 GO:002191~neural tube development E-02

5 GO: ~histone H4-K8 acetylation E-02 GO: ~histone H4-K acetylation E-02 GO: ~histone H4-K16 acetylation E-02 GO: ~protein localization to telomere E-02 GO: ~histone H4-K12 acetylation E-02 GO: ~neural tube formation E-02 GO:002193~central nervous system neuron differentiation E-02 GO: ~morphogenesis of an epithelium 10 2.E-02 GO: ~gastrulation E-02 GO: ~transmembrane receptor protein serine/threonine kinase signaling pathway E-02 GO: ~phospholipid metabolic process E-02 GO:003402~protein localization to chromosome E-02 GO: ~homotypic cell-cell adhesion E-02 GO: ~embryonic epithelial tube formation E-02 GO: ~morphogenesis of embryonic epithelium E-02 GO: ~neural tube closure 3.1E-02 GO: ~tube closure 3.1E-02 GO:003148~tube lumen formation 6 3.7E-02 GO:006041~respiratory system development E-02 GO:004343~protein amino acid acylation E-02 GO: ~apoptotic mitochondrial changes 3.90E-02 GO:001031~protein transport E-02 GO: ~organophosphate metabolic process E-02 GO: ~cell-cell adhesion E-02 GO: ~microtubule cytoskeleton organization E-02 GO:004184~establishment of protein localization E-02 GO: ~protein amino acid phosphorylation E-02 GO: ~primary neural tube formation 4.7E-02 GO: ~regulation of cell development E-02 GO: ~response to endoplasmic reticulum stress.22e-02 GO: ~regulation of JNK cascade 7.39E-02 GO: ~forebrain development 12.43E-02 GO: ~lung development 9.4E-02 GO: ~regulation of striated muscle tissue development 6.70E-02 GO:004216~cell-cell junction organization.70e-02 GO: ~wound healing 14.80E-02 GO: ~response to insulin stimulus 9.81E-02 GO: ~ncRNA metabolic process E-02 GO: ~germ cell development E-02 GO: ~regulation of muscle development E-02 GO: ~regulation of mitotic metaphase/anaphase transition E-02 GO: ~vesicle-mediated transport E-02

6 GO:001149~positive regulation of muscle cell differentiation E-02 GO:003292~regulation of activin receptor signaling pathway E-02 GO:000864~phospholipid biosynthetic process E-02 GO: ~respiratory tube development E-02 GO: ~protein amino acid acetylation 6 6.4E-02 GO: ~regulation of stress-activated protein kinase signaling pathway E-02 GO: ~protein import into nucleus E-02 GO: ~spermatid development E-02 GO: ~telomere maintenance via telomerase E-02 GO: ~receptor internalization E-02 GO: ~cell cycle process E-02 GO:001170~nuclear import 8 7.2E-02 GO: ~phosphorylation 43 7.E-02 GO: ~phosphate metabolic process 1 7.E-02 GO: ~phosphorus metabolic process 1 7.E-02 GO: ~ribonucleotide biosynthetic process E-02 GO: ~reproductive cellular process E-02 GO: ~protein complex assembly E-02 GO: ~protein complex biogenesis E-02 GO: ~peptidyl-serine modification 7.88E-02 GO: ~response to organic substance E-02 GO: ~membrane disassembly E-02 GO: ~SCF-dependent proteasomal ubiquitindependent protein catabolic process E-02 GO:001081~nuclear envelope disassembly E-02 GO:003239~tube morphogenesis E-02 GO:003336~protein localization in organelle E-02 GO: ~telomere maintenance via telomere lengthening E-02 GO: ~regulation of telomere maintenance E-02 GO:002192~central nervous system projection neuron axonogenesis E-02 GO: ~transmembrane receptor protein tyrosine kinase signaling pathway E-02 GO:000929~ribonucleotide metabolic process E-02 GO:00481~spermatid differentiation E-02 GO:004926~negative regulation of growth E-02 GO:004766~positive regulation of angiogenesis E-02

7 Supplementary Table S2 GO terms enriched by PCGs with low dosage sensitivity Category Term Count P-Value GO: ~keratinization E-03 GO: ~keratinocyte differentiation 7 3.6E-03 GO: ~epidermal cell differentiation 7.62E-03 GO:004761~regulation of adenylate cyclase activity 8.96E-03 GO: ~regulation of cyclase activity E-03 GO: ~regulation of camp biosynthetic process E-03 GO:001339~regulation of lyase activity E-03 GO: ~regulation of camp metabolic process E-03 GO: ~regulation of cyclic nucleotide biosynthetic 8 process 1.22E-02 GO: ~regulation of nucleotide biosynthetic process E-02 GO: ~regulation of cyclic nucleotide metabolic 8 process 1.40E-02 GO: ~regulation of nucleotide metabolic process E-02 GO:000731~positive regulation of peptidyl-tyrosine phosphorylation 2.11E-02 GO: ~nucleocytoplasmic transport 9 2.1E-02 GO:001169~nuclear transport E-02 GO: ~long-term memory E-02 GO:0008~transmembrane transport E-02 GO:00130~negative regulation of lyase activity 3.2E-02 GO: ~negative regulation of cyclase activity 3.2E-02 GO: ~activation of adenylate cyclase activity 3.2E-02 GO: ~negative regulation of adenylate cyclase activity 3.2E-02 GO:004762~positive regulation of adenylate cyclase activity 3.72E-02 GO: ~positive regulation of cyclase activity 3.94E-02 GO: ~learning or memory E-02 GO: ~G-protein signaling, coupled to camp 6 nucleotide second messenger 4.29E-02 GO:001349~positive regulation of lyase activity 4.38E-02 GO: ~sulfate transport E-02 GO:000993~dorsal/ventral pattern formation 4.61E-02 GO:001091~positive regulation of transcription factor activity 4.61E-02 GO: ~bone mineralization E-02 GO: ~positive regulation of protein amino acid 6 phosphorylation.06e-02 GO: ~regulation of hormone levels 8.0E-02 GO:000890~cognition 29.72E-02 GO:004874~branching morphogenesis of a tube.88e-02

8 GO: ~bone development 7.98E-02 GO:001078~regulation of adenylate cyclase activity 4 involved in G-protein signaling 6.08E-02 GO: ~inhibition of adenylate cyclase activity by G- 4 protein signaling 6.08E-02 GO:001079~positive regulation of adenylate cyclase 4 activity by G-protein signaling pathway 6.08E-02 GO: ~activation of adenylate cyclase activity by G- 4 protein signaling pathway 6.08E-02 GO:00099~detection of biotic stimulus E-02 GO: ~cAMP-mediated signaling 6 6.3E-02 GO: ~detection of lipopolysaccharide E-02 GO:000730~regulation of peptidyl-tyrosine phosphorylation 6.72E-02 GO:00327~positive regulation of interleukin-6 3 production 6.73E-02 GO: ~positive regulation of phosphorylation E-02 GO:003270~endocrine system development 7.01E-02 GO: ~epithelium development E-02 GO: ~positive regulation of DNA binding 7.31E-02 GO:001993~cyclic-nucleotide-mediated signaling E-02 GO:00497~positive regulation of cell differentiation E-02 GO:001062~positive regulation of phosphorus metabolic 6 process 7.E-02 GO:004937~positive regulation of phosphate metabolic 6 process 7.E-02 GO: ~secretion E-02 GO: ~regionalization E-02 GO:001090~regulation of transcription factor activity E-02 GO: ~morphogenesis of a branching structure 8.8E-02 GO: ~branching involved in lung morphogenesis E-02 GO: ~trachea development E-02 GO:002169~rhombomere 3 development E-02 GO:00308~epithelial cell differentiation E-02 GO: ~positive regulation of MAPKKK cascade E-02 GO: ~embryonic skeletal system development 9.9E-02 GO:000992~anterior/posterior pattern formation E-02 GO: ~hormone transport E-02 GO:001099~positive regulation of binding 9.94E-02 GO:001094~positive regulation of developmental process E-02

9 Supplementary table S3 GO terms enriched by lncrna ENSG Category Term Count P-Value GO: ~fatty acid metabolic process E-12 GO: ~fatty acid catabolic process 2.4E-07 GO:001939~fatty acid oxidation 3.41E-07 GO: ~lipid oxidation 3.41E-07 GO:003028~lipid modification 3.47E-06 GO: ~cellular lipid catabolic process.12e-06 GO:001604~organic acid catabolic process 2.31E-0 GO:004639~carboxylic acid catabolic process 2.31E-0 GO: ~lipid catabolic process 1.30E-04 GO: ~fatty acid biosynthetic process E-04 GO:00114~oxidation reduction E-04 GO:000663~fatty acid beta-oxidation E-04 GO:001603~organic acid biosynthetic process E-03 GO: ~carboxylic acid biosynthetic process E-03 GO:000161~fatty acid alpha-oxidation E-03 GO: ~lipid biosynthetic process E-02 GO: ~acyl-CoA metabolic process E-02 GO: ~very-long-chain fatty acid metabolic process E-02 GO:000843~fibroblast growth factor receptor signaling pathway E-02 GO:001781~positive regulation of cell division 2.89E-02 GO:001302~regulation of cell division 2 7.0E-02