Bioinformatics Network Analyses of Growth

Bioinformatics Network Analyses of Growth

Bioinformatics Network Analyses of Growth differentiation factor 11 anti-aging study Feng Zhang 1, 2, 3, 4, 5, Xia Yang 4 *, Zhijun Bao 1, 2, 3 * 1 Huadong Hospital Affiliated to Fudan University, 221 West Yan an Road, Shanghai, 200040, China. 2 National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, 12 Mid Urumqi Road, Shanghai, 200040, China. 3 Shanghai Key Laboratory of Clinical Geriatric Medicine, 221 West Yan an Road, Shanghai, 200040, China. 4 Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Dr. E, Terasaki Life Sciences Bldg. Rm 2000B, Los Angeles, CA90095, USA. 5 Department of Geriatrics, Huashan Hospital Affiliated to Fudan University, 12 Mid Urumqi Road, Shanghai, 200040, China. * These authors contributed equally to this work. 1 Supplementary Information Supplementary Table S1 GDF11 Genetic Co-expression Module Number of Each Human Tissue Tissue Module Amount Adipose Visceral omentum 1 Nervous System Cerebellum 1 Cerebellar hemisphere 1 Frontal cortex 1 Hippocampus 1 Nerve tibialis 1 Cardiovascular System Left ventricle 1 Digestive System Esophagus mucosa 1 Esophagus muscle 1 Stomach 1 Small intestine terminal ileum 1 Colon transverse 1 Colon sigmoid 1 Liver 1 Skeletal Muscle 1 Lung 1 Kidney 1 Endocrine System Pituitary 1 Thyroid 1 Adrenal gland 1 Female Reproduction Ovary 1 System Male Reproduction Testis 1 System Prostate 1 Total 23 2 Supplementary Table S2 Pathways and Functions of GDF11 Gene Co-expression Networks of Human Genes FDR belong Fold p- q- Tissue Top pathways/functions Overlaps to the Enrichment value value pathway Adipose Visceral Genes involved in Generic 121 352 6.35 1.79 1.92 omentum Transcription Pathway e-63 e-60 (Transcription) DNA replication 13 36 6.67 2.36 6.36 (Proliferation) e-8 e-6 Genes involved in Lagging 9 19 8.75 2.21 2.86 Strand Synthesis e-7 e-5 (Proliferation) Genes involved in DNA 11 30 6.77 2.39 2.86 strand elongation e-7 e-5 (Proliferation) Genes involved in Extension 10 27 6.84 7.63 8.21 of Telomeres (Telomere e-7 e-5 maintenance) Genes involved in Global 11 35 5.80 1.42 1.39 Genomic Nucleotide e-6 e-4 Excision Repair (DNA Repair) Genes involved in Processive 7 15 8.62 5.9 4.24 synthesis on the lagging e-6 e-4 strand (Proliferation) Base excision repair (DNA 10 35 5.27 1.11 6.67 Repair) e-5 e-4 Genes involved in Activation 9 31 5.36 2.67 1.2 of the pre-replicative e-5 e-3 complex (Proliferation) Caspase Cascade in 7 23 5.62 1.53 4.46 Apoptosis (Apoptosis) e-4 e-3 Mismatch repair (DNA 7 23 5.62 1.53 4.46 Repair) e-4 e-3 Genes involved in Formation 7 23 5.62 1.53 4.46 of incision complex in e-4 e-3 Global Genomic Nucleotide Excision Repair (DNA Repair) Genes involved in 6 17 6.52 1.84 4.79 Homologous recombination e-4 e-3 repair of replication- independent double-strand breaks (DNA Repair) Genes involved in 6 17 6.52 1.84 4.79 Inflammasomes (Immune) e-4 e-3 Genes involved in 7 24 5.38 2.06 4.93 Cholesterol biosynthesis e-4 e-3 (Metabolism of Cholesterol) Genes involved in Double- 7 24 5.38 2.06 4.93 Strand Break Repair (DNA e-4 e-3 Repair) 3 Genes involved in The 5 12 7.69 2.66 6.09 NLRP3 inflammasome e-4 e-3 (Immune) Genes involved in Base 6 19 5.83 3.67 7.61 Excision Repair (DNA e-4 e-3 Repair) Genes involved in Base 6 19 5.83 3.67 7.61 Excision Repair (DNA e-4 e-3 Repair) Genes involved in 5 13 7.10 4.12 8.08 Polymerase switching e-4 e-3 (Proliferation) Nervous Cerebellum Genes involved in NCAM 5 64 39.89 1.79 1.93 System signaling for neurite out- e-7 e-4 growth (NCAM signaling) Genes involved in NCAM1 4 39 52.37 1.07 5.3 interactions (NCAM e-6 e-4 signaling) Extracellular matrix (ECM)- 4 84 24.31 2.35 4.23 receptor interaction e-5 e-3 (Extracellular matrix) Cerebellar Multiple pathways from IGF- 5 23 21.12 3.27 1.09 hemisphere 1R signaling lead to BAD e-6 e-3 phosphorylation (IGF-1 signaling pathway) IL-2 Receptor Beta Chain in 5 38 12.78 4.29 3.35 T cell Activation (Immune) e-5 e-3 Genes involved in 5 38 12.78 4.29 3.35 PI3K/AKT activation e-5 e-3 (PI3K/AKT pathway) IGF-1 Signaling Pathway 4 21 18.50 5.77 3.89 (IGF-1 signaling pathway) e-5 e-3 Insulin Signaling Pathway 4 22 17.66 7 e- 4.43 (Insulin pathway) 5 e-3 CTCF: First Multivalent 4 23 16.89 8.4 4.59 Nuclear Factor (Apoptosis) e-5 e-3 Ras Signaling Pathway (Ras 4 23 16.89 8.4 4.59 pathway) e-5 e-3 Double Stranded RNA 3 10 29.14 1.23 5.44 Induced Gene Expression e-4 e-3 (Immune) Influence of Ras and Rho 4 26 14.94 1.38 5.44 proteins on G1 to S e-4 e-3 Transition (Cell cycle) Phospholipids as signalling 4 27 14.39 1.61 5.79 intermediaries (Cell e-4 e-3 survival) Inactivation of Gsk3 by AKT 4 27 14.39 1.61 5.79 causes accumulation of b- e-4 e-3 catenin in Alveolar Macrophages (AKT pathway) Growth Hormone Signaling 4 28 13.87 1.87 6.28 Pathway (Growth) e-4 e-3 4 Role of fl-arrestins in the 3 12 24.28 2.22 7.05 activation and targeting of e-4 e-3 MAP kinases (MAPK pathway) EGF Signaling Pathway 4 31 12.53 2.8 8.13 (EGF signaling) e-4 e-3 Circadian rhythm – mammal 3 13 22.42 2.87 8.13 (Circadian rhythm) e-4 e-3 Frontal Arginine and proline 11 54 11.47 2.47 1.33 cortex metabolism (Metabolism of e-9 e-6 amino acid) Alanine, aspartate and 8 32 14.07 6.89 1.48 glutamate metabolism e-8 e-5 (Metabolism of amino acid) Genes involved in tRNA 8 42 10.72 6.61 8.9 Aminoacylation e-7 e-5 (Expression) Genes involved in Cytosolic 6 24 14.07 3.15 3.77 tRNA aminoacylation e-6 e-4 (Expression) Aminoacyl-tRNA 7 41 9.61 7.21 6.36 biosynthesis (Expression) e-6 e-4 Genes involved in 5 21 13.40 2.8 1.89 Chondroitin sulfate e-5 e-3 biosynthesis (Metabolism of GAG) Proximal tubule bicarbonate 5 23 12.24 4.5 2.85 reclamation (Metabolism of e-5 e-3 ion) Genes involved in Inhibition 5 25 11.26 6.9 4.13 of voltage gated Ca2+ e-5 e-3 channels via G beta/gamma subunits (Ca2+ pathway) Genes involved in Amino 4 17 13.25 1.95 8.06 acid synthesis and e-4 e-3 interconversion (Metabolism of amino acid) Genes involved in Rap1 4 17 13.25 1.95 8.06 signaling (Rap1 signaling) e-4 e-3 Hippocampus Genes involved in 8 72 6.78 2.38 3.6 Metabolism of nucleotides e-5 e-3 (Metabolism of nucleotides) Sphingolipid metabolism 6 40 9.15 4.53 4.88 (Metabolism of e-5 e-3 sphingolipid) Genes involved in Apoptotic 6 40 9.15 4.53 4.88 cleavage of cellular proteins e-5 e-3 (Apoptosis) Axon guidance (Axon 10 129 4.73 5.62 5.5 guidance) e-5 e-3 Nerve tibia Genes involved in ER- 7 61 202.83 3.28 3.53 Phagosome pathway e-15 e-12 (Phagocytosis) 5 Genes involved in Antigen 7 76 162.79 1.63 5.86 processing-Cross e-14 e-12 presentation (Immune) Antigen processing and 6 89 119.15 9.92 1.23 presentation (Immune) e-12 e-9 Genes involved in 4 9 785.57 1.01 1.23 Endosomal/Vacuolar e-11 e-9 pathway (Phagocytosis) Genes involved in Interferon 5 64 138.08 2.87 3.09 alpha/beta signaling e-10 e-8 (Immune) Genes involved in Antigen 4 21 336.67 4.78 4.68 Presentation: Folding, e-10 e-8 assembly and peptide loading of class I MHC (Immune) Genes involved in Interferon 4 63 112.22 4.69 3.88 gamma signaling (Immune) e-8 e-6 Genes involved in 4 70 101.00 7.19 5.53 Immunoregulatory e-8 e-6 interactions between a Lymphoid and a non- Lymphoid cell (Immune) Allograft rejection 3 38 139.54 1.34 8.48 (Immune) e-6 e-5 Graft-versus-host disease 3 42 126.25 1.82 1.09 (Immune) e-6 e-4 Type I diabetes mellitus 3 44 120.51 2.1 1.19 (Immune) e-6 e-4 Proteasome (Proteasome 3 48 110.47 2.73 1.34 pathway) e-6 e-4 Genes involved in CDK- 3 48 110.47 2.73 1.34 mediated phosphorylation e-6 e-4 and removal of Cdc6 (DNA damage checkpoint) Genes involved in Cross- 3 48 110.47 2.73 1.34 presentation of soluble e-6 e-4 exogenous antigens (Immune) Genes involved in 3 49 108.21 2.91 1.36 Regulation of ornithine e-6 e-4 decarboxylase (ODC) (Metabolism of amino acid) Genes involved in 3 51 103.97 3.29 1.36 Autodegradation of the E3 e-6 e-4 ubiquitin ligase COP1 (DNA damage checkpoint) Genes involved in p53- 3 51 103.97 3.29 1.36 Independent G1/S DNA e-6 e-4 damage checkpoint (DNA damage checkpoint) Genes involved in SCF-beta- 3 51 103.97 3.29 1.36 TrCP mediated degradation e-6 e-4 of Emi1 (DNA damage checkpoint) 6 Genes involved in Vif- 3 52 101.97 3.49 1.37 mediated degradation of e-6 e-4 APOBEC3G (Proteasome pathway) Autoimmune thyroid disease 3 53 100.04 3.7 1.37 (Immune) e-6 e-4 Genes involved in 3 53 100.04 3.7 1.37 Destabilization of mRNA by e-6 e-4 AUF1 (hnRNP D0) (Metabolism of GDP) Cardiovascular Left ventricle Genes involved in G alpha 9 74 9.77 3.63 9.77 System (12/13) signalling events e-7 e-5 (GPCR pathway) Aminoacyl-tRNA 7 41 13.71 6.95 1.1 biosynthesis (Expression) e-7 e-4 Genes involved in NRAGE 7 43 13.07 9.75 1.17 signals death through JNK e-7 e-4 (Apoptosis) Genes involved in Cell death 7 60 9.37 9.74 6.14 signalling via NRAGE, e-6 e-4 NRIF and NADE (Apoptosis) Genes involved in trans- 7 60 9.37 9.74 6.14 Golgi Network Vesicle e-6 e-4 Budding (Vesicle-mediated transport) Genes involved in Double- 5 24 16.73 1.03 6.14 Strand Break Repair (DNA e-5 e-4 repair) Genes involved in tRNA 6 42 11.47 1.3 6.99 Aminoacylation e-5 e-4 (Expression) Glycerolipid metabolism 6 49 9.83 3.22 1.24 (Metabolism of e-5 e-3 glycerolipid) Genes involved in 6 49 9.83 3.22 1.24 Metabolism of non-coding e-5 e-3 RNA (Metabolism of non- coding RNA) Other glycan degradation 4 16 20.08 3.84 1.38 (Metabolism of glycan) e-5 e-3 Genes involved in 4 17 18.90 4.97 1.65 Homologous recombination e-5 e-3 repair of replication- independent double-strand breaks (DNA repair) Genes involved in RNA 5 33 12.17 5.22 1.65 Polymerase III Transcription e-5

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