#PPI is protein-protein interaction,TRI is transcriptional regulatory interaction.
#When interaction is TRI, Protein1 is transcription factor, Protein2 is target gene.

#sub networks deregulated initially from hepatitis C

#Interactions in sub network1
Protein1	Protein2	Interaction Type
CD74	CD74	PPI
CD74	HLA-DQB1	PPI
CD74	HLA-DPA1	PPI
CD74	HLA-DQA1	PPI
#GO	P value	Name	Type	Definition
GO:0050731	0.001277030	positive regulation of peptidyl-tyrosine phosphorylation	biological_process	Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine.
GO:0004896	0.0001703414	cytokine receptor activity	molecular_function	Combining with a cytokine to initiate a change in cell activity.
GO:0030890	0.0005960998	positive regulation of B cell proliferation	biological_process	Any process that activates or increases the rate or extent of B cell proliferation.
GO:0001961	0.0001703414	positive regulation of cytokine-mediated signaling pathway	biological_process	Any process that activates or increases the frequency, rate or extent of a cytokine mediated signaling pathway.
GO:0043518	0.000510959	negative regulation of DNA damage response, signal transduction by p53 class mediator	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of the cascade of processes induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage.
GO:0008283	0.001106830	cell proliferation	biological_process	The multiplication or reproduction of cells, resulting in the expansion of a cell population.
GO:0016021	0.001957613	integral to membrane	cellular_component	Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane.
GO:0001516	0.0003406611	prostaglandin biosynthetic process	biological_process	The chemical reactions and pathways resulting in the formation of prostaglandins, any of a group of biologically active metabolites which contain a cyclopentane ring.
GO:0002792	0.0001703414	negative regulation of peptide secretion	biological_process	Any process that stops, prevents, or reduces the frequency, rate, or extent of peptide secretion.
GO:0019955	0.0003406611	cytokine binding	molecular_function	Interacting selectively and non-covalently with a cytokine, any of a group of proteins that function to control the survival, growth and differentiation of tissues and cells, and which have autocrine and paracrine activity.
GO:0001540	0.0005960998	beta-amyloid binding	molecular_function	Interacting selectively and non-covalently with beta-amyloid peptide/protein and/or its precursor.
GO:0007165	0.003657547	signal transduction	biological_process	The process whereby an activated receptor conveys information down the signaling pathway, resulting in a change in the function or state of a cell.
GO:0048146	0.001277030	positive regulation of fibroblast proliferation	biological_process	Any process that activates or increases the frequency, rate or extent of multiplication or reproduction of fibroblast cells.
GO:0043066	0.004082191	negative regulation of apoptosis	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of cell death by apoptosis.
GO:0005773	0.0001703414	vacuole	cellular_component	A closed structure, found only in eukaryotic cells, that is completely surrounded by unit membrane and contains liquid material. Cells contain one or several vacuoles, that may have different functions from each other. Vacuoles have a diverse array of functions. They can act as a storage organelle for nutrients or waste products, as a degradative compartment, as a cost-effective way of increasing cell size, and as a homeostatic regulator controlling both turgor pressure and pH of the cytosol.
GO:0009986	0.005609786	cell surface	cellular_component	The external part of the cell wall and/or plasma membrane.
GO:0070374	0.000766365	positive regulation of ERK1 and ERK2 cascade	biological_process	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.

#sub networks deregulated initially from Cirrhosis

#Interactions in sub network1
Protein1	Protein2	Interaction Type
STAT1	CXCR4	PPI
PDGFRA	PDGFRA	PPI
CXCR4	CXCR4	PPI
PDGFRA	STAT1	PPI
#GO	P value	Name	Type	Definition
GO:0031252	0.0003406611	cell leading edge	cellular_component	The area of a motile cell closest to the direction of movement.
GO:0032027	0.0001703414	myosin light chain binding	molecular_function	Interacting selectively and non-covalently with a light chain of a myosin complex.
GO:0030335	0.001532290	positive regulation of cell migration	biological_process	Any process that activates or increases the frequency, rate or extent of cell migration.
GO:0048008	0.0009366086	platelet-derived growth factor receptor signaling pathway	biological_process	The series of molecular signals generated as a consequence of a platelet-derived growth factor receptor binding to one of its physiological ligands.
GO:0031410	0.0008514895	cytoplasmic vesicle	cellular_component	A vesicle formed of membrane or protein, found in the cytoplasm of a cell.
GO:0016023	0.0006812351	cytoplasmic membrane-bounded vesicle	cellular_component	A membrane-bounded vesicle found in the cytoplasm of the cell.
GO:0019838	0.001617365	growth factor binding	molecular_function	Interacting selectively and non-covalently with any growth factor, proteins or polypeptides that stimulate a cell or organism to grow or proliferate.
GO:0048407	0.001106830	platelet-derived growth factor binding	molecular_function	Interacting selectively and non-covalently with platelet-derived growth factor.
GO:0005887	0.002637847	integral to plasma membrane	cellular_component	Penetrating at least one phospholipid bilayer of a plasma membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer.
GO:0050920	0.0001703414	regulation of chemotaxis	biological_process	Any process that modulates the frequency, rate or extent of the directed movement of a motile cell or organism in response to a specific chemical concentration gradient.
GO:0019059	0.001106830	initiation of viral infection	biological_process	The set of processes involved in the start of virus infection of cells.
GO:0005018	0.0001703414	platelet-derived growth factor alpha-receptor activity	molecular_function	
GO:0018108	0.0009366086	peptidyl-tyrosine phosphorylation	biological_process	The posttranslational phosphorylation of peptidyl-tyrosine to form peptidyl-O4'-phospho-L-tyrosine.
GO:0005161	0.0009366086	platelet-derived growth factor receptor binding	molecular_function	Interacting selectively and non-covalently with the platelet-derived growth factor receptor.
GO:0048146	0.001277030	positive regulation of fibroblast proliferation	biological_process	Any process that activates or increases the frequency, rate or extent of multiplication or reproduction of fibroblast cells.
GO:0045740	0.002042661	positive regulation of DNA replication	biological_process	Any process that activates or increases the frequency, rate or extent of DNA replication.
GO:0001666	0.00391235	response to hypoxia	biological_process	A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.
GO:0005021	0.0003406611	vascular endothelial growth factor receptor activity	molecular_function	Combining with vascular endothelial growth factor to initiate a change in cell activity.
GO:0046777	0.002467821	protein amino acid autophosphorylation	biological_process	The phosphorylation by a protein of one or more of its own amino acid residues, or residues on an identical protein.
GO:0003779	0.001191933	actin binding	molecular_function	Interacting selectively and non-covalently with monomeric or multimeric forms of actin, including actin filaments.
GO:0009986	0.005609786	cell surface	cellular_component	The external part of the cell wall and/or plasma membrane.
GO:0008284	0.009082748	positive regulation of cell proliferation	biological_process	Any process that activates or increases the rate or extent of cell proliferation.
#Interactions in sub network2
Protein1	Protein2	Interaction Type
CCL5	VCAN	PPI
VCAN	VCAN	PPI
PLA2G2A	VCAN	PPI
#GO	P value	Name	Type	Definition
GO:0008347	0.0001916361	glial cell migration	biological_process	The orderly movement of a glial cell, non-neuronal cells that provide support and nutrition, maintain homeostasis, form myelin, and participate in signal transmission in the nervous system.
#Interactions in sub network3
Protein1	Protein2	Interaction Type
VWF	VWF	PPI
LUM	COL1A2	PPI
VWF	COL1A2	PPI
VWF	COL1A1	PPI
#GO	P value	Name	Type	Definition
GO:0005783	0.005864215	endoplasmic reticulum	cellular_component	The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
GO:0007596	0.0004258128	blood coagulation	biological_process	The sequential process by which the multiple coagulation factors of the blood interact, ultimately resulting in the formation of an insoluble fibrin clot; it may be divided into three stages: stage 1, the formation of intrinsic and extrinsic prothrombin converting principle; stage 2, the formation of thrombin; stage 3, the formation of stable fibrin polymers.
GO:0047485	0.005015931	protein N-terminus binding	molecular_function	Interacting selectively and non-covalently with a protein N-terminus, the end of any peptide chain at which the 2-amino (or 2-imino) function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue.
GO:0033093	0.0001703414	Weibel-Palade body	cellular_component	A large, elongated, rod-shaped secretory granule characteristic of vascular endothelial cells that contain a number of structurally and functionally distinct proteins, of which the best characterized are von Willebrand factor (VWF) and P-selectin. Weibel-Palade bodies are formed from the trans-Golgi network in a process that depends on VWF, which is densely packed in a highly organized manner, and on coat proteins that remain associated with the granules. Upon cell stimulation, regulated exocytosis releases the contained proteins to the cell surface, where they act in the recruitment of platelets and leukocytes and in inflammatory and vasoactive responses.
GO:0019865	0.0001703414	immunoglobulin binding	molecular_function	Interacting selectively and non-covalently with an immunoglobulin.
GO:0030168	0.0006812351	platelet activation	biological_process	A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.
GO:0051087	0.0008514895	chaperone binding	molecular_function	Interacting selectively and non-covalently with a chaperone protein, a class of proteins that bind to nascent or unfolded polypeptides and ensure correct folding or transport.
GO:0051260	0.001702435	protein homooligomerization	biological_process	The process of creating protein oligomers, compounds composed of a small number, usually between three and ten, of identical component monomers. Oligomers may be formed by the polymerization of a number of monomers or the depolymerization of a large protein polymer.
GO:0005178	0.001106830	integrin binding	molecular_function	Interacting selectively and non-covalently with an integrin.
GO:0005576	7.569073e-07	extracellular region	cellular_component	The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
GO:0007599	0.0001703414	hemostasis	biological_process	The stopping of bleeding (loss of body fluid) or the arrest of the circulation to an organ or part.
GO:0031012	0.0006812351	extracellular matrix	cellular_component	A structure lying external to one or more cells, which provides structural support for cells or tissues; may be completely external to the cell (as in animals) or be part of the cell (as in plants).
GO:0043231	0.003232767	intracellular membrane-bounded organelle	cellular_component	Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane.
GO:0002020	0.001362122	protease binding	molecular_function	Interacting selectively and non-covalently with any protease or peptidase.
GO:0031589	0.0001703414	cell-substrate adhesion	biological_process	The attachment of a cell to the underlying substrate via adhesion molecules.
GO:0007155	0.000766365	cell adhesion	biological_process	The attachment of a cell, either to another cell or to an underlying substrate such as the extracellular matrix, via cell adhesion molecules.
GO:0005518	0.000510959	collagen binding	molecular_function	Interacting selectively and non-covalently with collagen, a group of fibrous proteins of very high tensile strength that form the main component of connective tissue in animals. Collagen is highly enriched in glycine (some regions are 33% glycine) and proline, occurring predominantly as 3-hydroxyproline (about 20%).
GO:0001948	0.0009366086	glycoprotein binding	molecular_function	Interacting selectively and non-covalently with a glycoprotein, a protein that contains covalently bound glycose (monosaccharide) residues. These also include proteoglycans.

#sub networks deregulated initially from BCLC stage 0 HCC

#Interactions in sub network1
Protein1	Protein2	Interaction Type
ATXN1	EIF1AY	PPI
EIF5	EIF1AY	PPI
ATXN1	ATXN1	PPI
#GO	P value	Name	Type	Definition
GO:0043231	0.002425582	intracellular membrane-bounded organelle	cellular_component	Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane.
GO:0043621	0.0004471129	protein self-association	molecular_function	Interacting selectively and non-covalently with a domain within the same polypeptide.
GO:0016363	0.001021777	nuclear matrix	cellular_component	The dense fibrillar network lying on the inner side of the nuclear membrane.
GO:0042405	0.0001277602	nuclear inclusion body	cellular_component	An intranuclear focus at which aggregated proteins have been sequestered.
GO:0005737	0.005216753	cytoplasm	cellular_component	All of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
GO:0042272	0.0001277602	nuclear RNA export factor complex	cellular_component	A protein complex that contains two proteins (know in several organisms, including Drosophila, as NXF1 and NXF2) and is required for the export of the majority of mRNAs from the nucleus to the cytoplasm; localized in the nucleoplasm and at both the nucleoplasmic and cytoplasmic faces of the nuclear pore complex; shuttles between the nucleus and the cytoplasm.
GO:0016481	0.003764352	negative regulation of transcription	biological_process	Any cellular process that stops, prevents or reduces the frequency, rate or extent of transcription.
GO:0051168	0.0001916361	nuclear export	biological_process	The directed movement of substances out of the nucleus.
GO:0008022	0.006183841	protein C-terminus binding	molecular_function	Interacting selectively and non-covalently with a protein C-terminus, the end of any peptide chain at which the 1-carboxy function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue.
GO:0008266	0.0001277602	poly(U) RNA binding	molecular_function	Interacting selectively and non-covalently with a sequence of uracil residues in an RNA molecule.
GO:0034046	0.0001277602	poly(G) RNA binding	molecular_function	Interacting selectively and non-covalently with a sequence of guanine residues in an RNA molecule.
GO:0016564	0.002744446	transcription repressor activity	molecular_function	Any transcription regulator activity that prevents or downregulates transcription.
#Interactions in sub network2
Protein1	Protein2	Interaction Type
SHBG	SHBG	PPI
DPT	DCN	PPI
PTK2	PTK2	PPI
CD36	ITGA6	PPI
IGHM	PTK2	PPI
CD36	COL1A1	PPI
CXCR4	PTPRC	PPI
THBS1	COL3A1	PPI
PLA2G2A	DCN	PPI
COL1A2	SHBG	PPI
PTPRC	INSR	PPI
DCN	COL4A1	PPI
IGF2	IGFBP3	PPI
INSR	IGF2	PPI
GHR	GHR	PPI
KPNB1	IGFBP3	PPI
INSR	SOCS2	PPI
DCN	COL1A1	PPI
CXCL12	CXCR4	PPI
SERPINE2	COL4A1	PPI
PTK2	SOCS2	PPI
THBS1	TFPI	PPI
DCN	COL1A2	PPI
GPC3	IGF2	PPI
CTSB	IGF1	PPI
MARCKS	CTSB	PPI
FN1	COL4A2	PPI
THBS1	CD36	PPI
IFNAR1	PTPRC	PPI
IGFBP3	COL1A1	PPI
IGF1	IGFBP3	PPI
IGFALS	IGF1	PPI
DDX3Y	SHBG	PPI
CD36	COL1A2	PPI
FN1	COL1A2	PPI
SOCS2	GHR	PPI
IGFBP3	FN1	PPI
CTSB	CTSB	PPI
IGFALS	IGFBP3	PPI
CXCL12	CXCL12	PPI
INSR	INSR	PPI
#GO	P value	Name	Type	Definition
GO:0008233	0.006090813	peptidase activity	molecular_function	Catalysis of the hydrolysis of a peptide bond. A peptide bond is a covalent bond formed when the carbon atom from the carboxyl group of one amino acid shares electrons with the nitrogen atom from the amino group of a second amino acid.
GO:0031623	0.007824388	receptor internalization	biological_process	The process by which cell surface receptors are monoubiquitinated following ligand-induced activation, and subsequently taken up into endocytic vesicles and targeted to the lysosome or vacuole for degradation; serves as a mechanism to downregulate receptor signaling.
GO:0042593	0.007824388	glucose homeostasis	biological_process	Any process involved in the maintenance of an internal steady-state of glucose within an organism or cell.
GO:0044236	0.001743938	multicellular organismal metabolic process	biological_process	The chemical reactions and pathways in multicellular organisms that occur at the tissue, organ, or organismal level. These processes, unlike cellular metabolism, can include transport of substances between cells when that transport is required.
GO:0005887	0.0003621887	integral to plasma membrane	cellular_component	Penetrating at least one phospholipid bilayer of a plasma membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer.
GO:0005792	0.00695797	microsome	cellular_component	Any of the small, heterogeneous, artifactual, vesicular particles, 50-150 nm in diameter, that are formed when some eukaryotic cells are homogenized and that sediment on centrifugation at 100000 g.
GO:0060267	0.001743938	positive regulation of respiratory burst	biological_process	Any process that increases the rate frequency or extent of a phase of elevated metabolic activity, during which oxygen consumption increases; this leads to the production, by an NADH dependent system, of hydrogen peroxide (H2O2), superoxide anions and hydroxyl radicals.
GO:0090026	0.003484910	positive regulation of monocyte chemotaxis	biological_process	Any process that increases the frequency, rate, or extent of monocyte chemotaxis.
GO:0051290	0.001743938	protein heterotetramerization	biological_process	The formation of a protein heterotetramer, a macromolecular structure consisting of four noncovalently associated subunits, of which not all are identical.
GO:0004197	0.008690069	cysteine-type endopeptidase activity	molecular_function	Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which the sulfhydryl group of a cysteine residue at the active center acts as a nucleophile.
GO:0045429	0.00695797	positive regulation of nitric oxide biosynthetic process	biological_process	Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of nitric oxide.
GO:0010008	0.005222918	endosome membrane	cellular_component	The lipid bilayer surrounding an endosome.
GO:0048639	0.001743938	positive regulation of developmental growth	biological_process	Any process that activates, maintains or increases the rate of developmental growth.
GO:0003007	0.003484910	heart morphogenesis	biological_process	The developmental process by which the heart is generated and organized. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood.
GO:0043559	0.006090813	insulin binding	molecular_function	Interacting selectively and non-covalently with insulin, a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms.
GO:0017046	0.002614795	peptide hormone binding	molecular_function	Interacting selectively and non-covalently with any peptide with hormonal activity in animals.
GO:0005159	0.0001396648	insulin-like growth factor receptor binding	molecular_function	Interacting selectively and non-covalently with the insulin-like growth factor receptor.
GO:0005886	0.008974016	plasma membrane	cellular_component	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
GO:0045840	4.063101e-05	positive regulation of mitosis	biological_process	Any process that activates or increases the frequency, rate or extent of mitosis.
GO:0018108	0.009555012	peptidyl-tyrosine phosphorylation	biological_process	The posttranslational phosphorylation of peptidyl-tyrosine to form peptidyl-O4'-phospho-L-tyrosine.
GO:0051425	0.001743938	PTB domain binding	molecular_function	Interacting selectively and non-covalently with a phosphotyrosine-binding (PTB) domain of a protein.
GO:0043548	0.00695797	phosphoinositide 3-kinase binding	molecular_function	Interacting selectively and non-covalently with a phosphoinositide 3-kinase, any enzyme that catalyzes the addition of a phosphate group to an inositol lipid at the 3' position of the inositol ring.
GO:0032870	4.873025e-05	cellular response to hormone stimulus	biological_process	A change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hormone stimulus.
GO:0031994	0.004354284	insulin-like growth factor I binding	molecular_function	Interacting selectively and non-covalently with insulin-like growth factor I.
GO:0005615	3.439435e-06	extracellular space	cellular_component	That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.
GO:0031995	0.001743938	insulin-like growth factor II binding	molecular_function	Interacting selectively and non-covalently with insulin-like growth factor II.
GO:0004716	0.001743938	receptor signaling protein tyrosine kinase activity	molecular_function	
GO:0018149	0.007824388	peptide cross-linking	biological_process	The formation of a covalent cross-link between or within protein chains.
GO:0045821	0.003484910	positive regulation of glycolysis	biological_process	Any process that activates or increases the frequency, rate or extent of glycolysis.
GO:0070195	0.001743938	growth hormone receptor complex	cellular_component	A receptor complex that consists of two identical subunits and binds growth hormone.
GO:0032355	5.755845e-05	response to estradiol stimulus	biological_process	A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of stimulus by estradiol, a C18 steroid hormone hydroxylated at C3 and C17 that acts as a potent estrogen.
GO:0060396	1.554802e-05	growth hormone receptor signaling pathway	biological_process	The series of molecular signals generated as a consequence of growth hormone receptor binding to its physiological ligand.
GO:0046898	0.001743938	response to cycloheximide	biological_process	A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cycloheximide stimulus. Cycloheximide (actidione) is an antibiotic produced by some Streptomyces species which interferes with protein synthesis in eukaryotes.
GO:0032583	0.001743938	regulation of gene-specific transcription	biological_process	Any process that modulates the DNA-dependent transcription of a specific gene or genes.
GO:0032147	0.005222918	activation of protein kinase activity	biological_process	Any process that initiates the activity of an inactive protein kinase.
GO:0032148	0.004354284	activation of protein kinase B activity	biological_process	Any process that initiates the activity of the inactive enzyme protein kinase B.
GO:0051897	7.739688e-05	positive regulation of protein kinase B signaling cascade	biological_process	Any process that activates or increases the frequency, rate or extent of the protein kinase B signaling cascade, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B.
GO:0005009	0.001743938	insulin receptor activity	molecular_function	Combining with insulin to initiate a change in cell activity.
GO:0007186	0.001665056	G-protein coupled receptor protein signaling pathway	biological_process	The series of molecular signals generated as a consequence of a G-protein coupled receptor binding to its physiological ligand.
GO:0000187	0.009555012	activation of MAPK activity	biological_process	The initiation of the activity of the inactive enzyme MAP kinase by phosphorylation by a MAPKK.
GO:0030169	0.003484910	low-density lipoprotein binding	molecular_function	Interacting selectively and non-covalently with low-density lipoprotein, one of the classes of lipoproteins found in blood plasma in many animals (data normally relate to humans).
GO:0045995	0.001743938	regulation of embryonic development	biological_process	Any process that modulates the frequency, rate or extent of embryonic development.
GO:0042169	0.0002024334	SH2 domain binding	molecular_function	Interacting selectively and non-covalently with a SH2 domain (Src homology 2) of a protein, a protein domain of about 100 amino-acid residues and belonging to the alpha + beta domain class.
GO:0005899	0.002614795	insulin receptor complex	cellular_component	A disulfide-bonded, heterotetrameric receptor complex. The alpha chains are entirely extracellular, while each beta chain has one transmembrane domain. The ligand binds to the alpha subunit extracellular domain and the kinase is associated with the beta subunit intracellular domain.
GO:0019087	0.001743938	transformation of host cell by virus	biological_process	Any virus-induced change in the morphological, biochemical, or growth parameters of a cell.
GO:0043560	0.004354284	insulin receptor substrate binding	molecular_function	Interacting selectively and non-covalently with any of the insulin receptor substrate (IRS) proteins, adaptor proteins that bind to the transphosphorylated insulin and insulin-like growth factor receptors, are themselves phosphorylated and in turn recruit SH2 domain-containing signaling molecules to form a productive signaling complex.
GO:0040018	0.003484910	positive regulation of multicellular organism growth	biological_process	Any process that activates or increases the frequency, rate or extent of growth of an organism to reach its usual body size.
GO:0043410	7.739688e-05	positive regulation of MAPKKK cascade	biological_process	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the MAPK cascade.
#Interactions in sub network3
Protein1	Protein2	Interaction Type
NCOR1	TBL1X	PPI
ESR1	DUT	PPI
LEF1	CTNNB1	PPI
HBA2	HBA2	PPI
ESR1	MLL2	PPI
ETS2	NCOR1	PPI
FOS	LMNA	PPI
ESR1	FOS	TRI
SMARCA4	ESR1	PPI
SPEN	SOX9	PPI
KPNA2	KPNA2	PPI
CDKN2C	CDK6	PPI
CHD9	ESR1	PPI
CDKN2A	CDKN2A	PPI
FOS	HBA1	TRI
HBA1	HBB	PPI
NR1H4	ESR1	PPI
HSP90AB1	ESR1	PPI
TBL1XR1	NCOR1	PPI
NCOA2	ESR1	PPI
ESR1	CTNNB1	PPI
EGR1	CDKN2A	PPI
HBG2	HBB	PPI
LMNA	LMNA	PPI
SMARCA4	SMARCC1	PPI
CBFA2T2	NCOR1	PPI
GADD45B	ESR1	PPI
NCOR1	NCOR1	PPI
HBB	HBA2	PPI
CDKN2A	HSP90AB1	PPI
HSPA4	KPNA2	PPI
SMARCA4	TMF1	PPI
SOS1	SOS1	PPI
CDKN2C	CDKN2A	PPI
ESR1	HSPA4	PPI
ESR1	SOS1	PPI
CTNNB1	CDK6	PPI
SPEN	NCOR1	PPI
SMARCA4	CTNNB1	PPI
HBG2	HBG2	PPI
NCOR1	ESR1	PPI
SH3KBP1	SOS1	PPI
CDK6	CDK6	PPI
CDK6	CDKN2A	PPI
#GO	P value	Name	Type	Definition
GO:0005737	0.0004664751	cytoplasm	cellular_component	All of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
GO:0004693	0.004671996	cyclin-dependent protein kinase activity	molecular_function	Catalysis of the reaction: ATP + a protein = ADP + a phosphoprotein; dependent on the binding of a regulatory cyclin subunit and full activity requires stimulatory phosphorylation by a CDK-activating kinase (CAK).
GO:0045668	0.002805763	negative regulation of osteoblast differentiation	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of osteoblast differentiation.
GO:0006917	0.0009793533	induction of apoptosis	biological_process	A process that directly activates any of the steps required for cell death by apoptosis.
GO:0032088	0.008394228	negative regulation of NF-kappaB transcription factor activity	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of the activity of the transcription factor NF-kappaB.
GO:0030332	0.001871365	cyclin binding	molecular_function	Interacting selectively and non-covalently with cyclins, proteins whose levels in a cell varies markedly during the cell cycle, rising steadily until mitosis, then falling abruptly to zero. As cyclins reach a threshold level, they are thought to drive cells into G2 phase and thus to mitosis.
GO:0008285	0.001232282	negative regulation of cell proliferation	biological_process	Any process that stops, prevents or reduces the rate or extent of cell proliferation.
GO:0051225	0.003739306	spindle assembly	biological_process	The aggregation, arrangement and bonding together of a set of components to form the spindle, the array of microtubules and associated molecules that serves to move duplicated chromosomes apart.
GO:0042826	0.0007901578	histone deacetylase binding	molecular_function	Interacting selectively and non-covalently with the enzyme histone deacetylase.
GO:0070215	0.002805763	MDM2 binding	molecular_function	Interacting selectively and non-covalently with any isoform of the MDM2 protein, a negative regulator of p53.
GO:0045736	0.003739306	negative regulation of cyclin-dependent protein kinase activity	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of CDK activity.
GO:0000075	0.005603832	cell cycle checkpoint	biological_process	The cell cycle regulatory process by which progression through the cycle can be halted until conditions are suitable for the cell to proceed to the next stage.
GO:0016055	0.008394228	Wnt receptor signaling pathway	biological_process	The series of molecular signals initiated by binding of Wnt protein to a frizzled family receptor on the surface of the target cell and ending with a change in cell state.
GO:0001954	0.003739306	positive regulation of cell-matrix adhesion	biological_process	Any process that activates or increases the rate or extent of cell adhesion to an extracellular matrix.
GO:0043697	0.001871365	cell dedifferentiation	biological_process	The process whereby a specialized cell loses the structural or functional features that characterize it in the mature organism, or some other relatively stable phase of the organism's life history. Under certain conditions, these cells can revert back to the features of the stem cells that were their ancestors.
GO:0046329	0.007464947	negative regulation of JNK cascade	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of signal transduction mediated by the JNK cascade.
GO:0030308	0.001019554	negative regulation of cell growth	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of cell growth.
GO:0045646	0.001871365	regulation of erythrocyte differentiation	biological_process	Any process that modulates the frequency, rate or extent of erythrocyte differentiation.
GO:0042063	0.001871365	gliogenesis	biological_process	The process by which glial cells are generated. This includes the production of glial progenitors and their differentiation into mature glia.
GO:0007517	0.001871365	muscle organ development	biological_process	The process whose specific outcome is the progression of the muscle over time, from its formation to the mature structure. The muscle is an organ consisting of a tissue made up of various elongated cells that are specialized to contract and thus to produce movement and mechanical work.
GO:0046825	0.001871365	regulation of protein export from nucleus	biological_process	Any process that modulates the frequency, rate or extent of the directed movement of proteins from the nucleus to the cytoplasm.
GO:0006469	0.009322658	negative regulation of protein kinase activity	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of protein kinase activity.
GO:0005088	0.001871365	Ras guanyl-nucleotide exchange factor activity	molecular_function	Stimulates the exchange of guanyl nucleotides associated with a GTPase of the Ras superfamily. Under normal cellular physiological conditions, the concentration of GTP is higher than that of GDP, favoring the replacement of GDP by GTP in association with the GTPase.
GO:0050680	0.006534815	negative regulation of epithelial cell proliferation	biological_process	Any process that stops, prevents or reduces the rate or extent of epithelial cell proliferation.
GO:0007265	0.003255111	Ras protein signal transduction	biological_process	A series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state.
GO:0000080	0.004671996	G1 phase of mitotic cell cycle	biological_process	A cell cycle process comprising the steps by which a cell progresses through G1 phase, one of two 'gap' phases in the mitotic cell cycle; G1 is the interval between the completion of mitosis and the beginning of DNA synthesis.
GO:0006338	0.005603832	chromatin remodeling	biological_process	Dynamic structural changes to eukaryotic chromatin occurring throughout the cell division cycle. These changes range from the local changes necessary for transcriptional regulation to global changes necessary for chromosome segregation.
GO:0019901	0.001821703	protein kinase binding	molecular_function	Interacting selectively and non-covalently with a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
GO:0017053	2.749175e-06	transcriptional repressor complex	cellular_component	A protein complex that possesses activity that prevents or downregulates transcription.
GO:0005515	2.337228e-06	protein binding	molecular_function	Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
GO:0000118	9.14141e-08	histone deacetylase complex	cellular_component	A protein complex that possesses histone deacetylase activity.
GO:0043517	0.002805763	positive regulation of DNA damage response, signal transduction by p53 class mediator	biological_process	Any process that activates, maintains or increases the rate of the cascade of processes induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage.
GO:0006309	0.005603832	DNA fragmentation involved in apoptosis	biological_process	The cleavage of DNA during apoptosis, which usually occurs in two stages: cleavage into fragments of about 50 kbp followed by cleavage between nucleosomes to yield 200 bp fragments.
GO:0042326	1.793101e-05	negative regulation of phosphorylation	biological_process	Any process that stops, prevents or decreases the rate of addition of phosphate groups to a molecule.
GO:0010389	0.002805763	regulation of G2/M transition of mitotic cell cycle	biological_process	Any process that modulates the rate or extent of progression from G2 phase to M phase of the mitotic cell cycle.
GO:0000082	0.0001297871	G1/S transition of mitotic cell cycle	biological_process	Progression from G1 phase to S phase of the mitotic cell cycle.
GO:0001953	0.002805763	negative regulation of cell-matrix adhesion	biological_process	Any process that stops, prevents or reduces the rate or extent of cell adhesion to the extracellular matrix.
GO:0032993	0.004671996	protein-DNA complex	cellular_component	A macromolecular complex containing both protein and DNA molecules.
GO:0003714	5.815443e-06	transcription corepressor activity	molecular_function	The function of a transcription cofactor that represses transcription from a RNA polymerase II promoter; does not bind DNA itself.
GO:0008637	0.001871365	apoptotic mitochondrial changes	biological_process	The morphological and physiological alterations undergone by mitochondria during apoptosis.
GO:0007050	0.0009013095	cell cycle arrest	biological_process	The process by which the cell cycle is halted during one of the normal phases (G1, S, G2, M).
GO:0031648	0.002805763	protein destabilization	biological_process	Any process that decreases the stability of a protein, making it more vulnerable to degradative processes or aggregation.
GO:0005876	7.338349e-07	spindle microtubule	cellular_component	Any microtubule that is part of a mitotic or meiotic spindle; anchored at one spindle pole.
GO:0005634	3.215447e-07	nucleus	cellular_component	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
GO:0010553	2.922078e-05	negative regulation of gene-specific transcription from RNA polymerase II promoter	biological_process	Any process that decreases the frequency, rate or extent of the specifically regulated synthesis of RNA from DNA encoding a specific gene or set of genes by RNA polymerase II (Pol II), originating at a Pol II-specific promoter.
GO:0004861	8.548755e-06	cyclin-dependent protein kinase inhibitor activity	molecular_function	Stops, prevents or reduces the activity of a cyclin-dependent protein kinase.
GO:0071158	0.001871365	positive regulation of cell cycle arrest	biological_process	Any process that increases the rate, frequency, or extent of cell cycle arrest, the process by which the cell cycle is halted during one of the normal phases.
GO:0051059	0.009322658	NF-kappaB binding	molecular_function	Interacting selectively and non-covalently with NF-kappaB, a transcription factor for eukaryotic RNA polymerase II promoters.
GO:0050821	0.007464947	protein stabilization	biological_process	Any process involved in maintaining the structure and integrity of a protein and preventing it from degradation or aggregation.
GO:0044428	0.001871365	nuclear part	cellular_component	Any constituent part of the nucleus, a membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated.
#Interactions in sub network4
Protein1	Protein2	Interaction Type
TFPI2	F11	PPI
HGF	LCN2	PPI
TGFBR1	TGFBR1	PPI
SMURF2	DAB2	PPI
DAB2	TGFBR1	PPI
DAB2	MYO6	PPI
SMURF2	SF3A2	PPI
SMURF2	TFPI2	PPI
CHN2	TGFBR1	PPI
RACGAP1	CHN2	PPI
F11	HGF	PPI
LCN2	LCN2	PPI
#GO	P value	Name	Type	Definition
GO:0005025	0.0007662509	transforming growth factor beta receptor activity, type I	molecular_function	Combining with a complex of transforming growth factor beta and a type II TGF-beta receptor to initiate a change in cell activity.
GO:0051897	0.003571235	positive regulation of protein kinase B signaling cascade	biological_process	Any process that activates or increases the frequency, rate or extent of the protein kinase B signaling cascade, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B.
GO:0019838	0.00484384	growth factor binding	molecular_function	Interacting selectively and non-covalently with any growth factor, proteins or polypeptides that stimulate a cell or organism to grow or proliferate.
GO:0030307	0.001531963	positive regulation of cell growth	biological_process	Any process that activates or increases the frequency, rate or extent of cell growth.
GO:0043235	0.003571235	receptor complex	cellular_component	Any protein complex that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.
GO:0010862	0.006369	positive regulation of pathway-restricted SMAD protein phosphorylation	biological_process	Any process that increases the rate, frequency or extent of SMAD protein nuclear translocation. SMAD protein nuclear translocation is the vectorial transfer of a SMAD proteins from the cytoplasm into the nucleus, through the nuclear pore. Pathway-restricted SMAD proteins and common-partner SMAD proteins are involved in the transforming growth factor beta receptor signaling pathways.
GO:0051272	0.001276786	positive regulation of cellular component movement	biological_process	Any process that activates or increases the frequency, rate or extent of the movement of a cellular component.
GO:0048870	0.001276786	cell motility	biological_process	Any process involved in the controlled self-propelled movement of a cell that results in translocation of the cell from one place to another.
GO:0050431	0.004589438	transforming growth factor beta binding	molecular_function	Interacting selectively and non-covalently with TGF-beta, transforming growth factor beta, a multifunctional peptide that controls proliferation, differentiation and other functions in many cell types.
GO:0000186	0.001021548	activation of MAPKK activity	biological_process	The initiation of the activity of the inactive enzyme MAP kinase kinase by phosphorylation by a MAPKKK.
GO:0070723	0.002297138	response to cholesterol	biological_process	A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cholesterol stimulus.
GO:0044459	0.0005108937	plasma membrane part	cellular_component	Any constituent part of the plasma membrane, the membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
GO:0005114	0.004589438	type II transforming growth factor beta receptor binding	molecular_function	Interacting selectively and non-covalently with a type II transforming growth factor beta receptor.
GO:0060391	0.002042140	positive regulation of SMAD protein nuclear translocation	biological_process	Any process that increases the rate, frequency or extent of SMAD protein nuclear translocation. SMAD protein nuclear translocation is the vectorial transfer of a SMAD proteins from the cytoplasm into the nucleus, through the nuclear pore. Pathway-restricted SMAD proteins and common-partner SMAD proteins are involved in the transforming growth factor beta receptor signaling pathways.
GO:0005024	0.002806956	transforming growth factor beta receptor activity	molecular_function	Combining with transforming growth factor beta to initiate a change in cell activity.
GO:0045885	0.001021548	positive regulation of survival gene product expression	biological_process	Any process that activates or increases the frequency, rate or extent of survival gene product expression; survival gene products are those that antagonize the apoptotic program. Regulation can be at the transcriptional, translational, or posttranslational level.
GO:0018107	0.001787081	peptidyl-threonine phosphorylation	biological_process	The posttranslational phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine.
GO:0018105	0.004080456	peptidyl-serine phosphorylation	biological_process	The posttranslational phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
GO:0060389	0.00484384	pathway-restricted SMAD protein phosphorylation	biological_process	The process of introducing a phosphate group on to a pathway restricted SMAD protein. A pathway restricted SMAD protein is an effector protein that acts directly downstream of the transforming growth factor family receptor.
GO:0046332	0.008906171	SMAD binding	molecular_function	Interacting selectively and non-covalently with a SMAD signaling protein.
GO:0004675	0.001531963	transmembrane receptor protein serine/threonine kinase activity	molecular_function	Catalysis of the reaction: ATP + receptor-protein serine/threonine = ADP + receptor-protein serine/threonine phosphate.
GO:0045449	0.007130776	regulation of transcription	biological_process	Any process that modulates the frequency, rate or extent of the synthesis of either RNA on a template of DNA or DNA on a template of RNA.
#Interactions in sub network5
Protein1	Protein2	Interaction Type
PON1	ALB	PPI
CLU	LEPR	PPI
ALB	AGA	PPI
C7	CLU	PPI
CLU	PON1	PPI
AGA	AGA	PPI
#GO	P value	Name	Type	Definition
GO:0005615	8.858628e-05	extracellular space	cellular_component	That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.
GO:0003948	0.0002554958	N4-(beta-N-acetylglucosaminyl)-L-asparaginase activity	molecular_function	Catalysis of the reaction: N(4)-(beta-N-acetyl-D-glucosaminyl)-L-asparagine + H2O = N-acetyl-beta-glucosaminylamine + L-aspartate.
GO:0005764	0.0007663243	lysosome	cellular_component	A small lytic vacuole that has cell cycle-independent morphology and is found in most animal cells and that contains a variety of hydrolases, most of which have their maximal activities in the pH range 5-6. The contained enzymes display latency if properly isolated. About 40 different lysosomal hydrolases are known and lysosomes have a great variety of morphologies and functions.
GO:0034366	0.0007663243	spherical high-density lipoprotein particle	cellular_component	A mature high-density lipoprotein (HDL) particle, converted from discoidal HDL particles following the esterification of cholesterol in the particle by phosphatidylcholine-sterol O-acyltransferase (lecithin cholesterol acyltransferase; LCAT).
GO:0006517	0.0002554958	protein deglycosylation	biological_process	The removal of sugar residues from a glycosylated protein.
#Interactions in sub network6
Protein1	Protein2	Interaction Type
STAT1	MDK	PPI
STAT1	CYBB	TRI
MDK	MDK	PPI
#GO	P value	Name	Type	Definition
GO:0008201	0.0009579359	heparin binding	molecular_function	Interacting selectively and non-covalently with heparin, any member of a group of glycosaminoglycans found mainly as an intracellular component of mast cells and which consist predominantly of alternating alpha1-4-linked D-galactose and N-acetyl-D-glucosamine-6-sulfate residues.

#sub networks deregulated initially from BCLC stage A HCC

#Interactions in sub network1
Protein1	Protein2	Interaction Type
ATF3	NUF2	PPI
NDC80	NUF2	PPI
AURKA	NUF2	PPI
#GO	P value	Name	Type	Definition
GO:0031262	0.0002555094	Ndc80 complex	cellular_component	A protein complex conserved among eukaryotes that forms part of the kinetochore and plays an essential role in forming stable kinetochore-microtubule attachments. The complex contains proteins known in several species, including budding and fission yeasts, as Ndc80p, Nuf2p, Spc24p, and Spc25p. In vertebrates it is part of the outer plate of the kinetochore.
#Interactions in sub network2
Protein1	Protein2	Interaction Type
MNDA	CDC2	PPI
CDC2	ECT2	PPI
DAB2	CDC2	PPI
BIRC5	BIRC5	PPI
CDC2	BIRC5	PPI
CDC2	KIF11	PPI
KIF11	KIF11	PPI
#GO	P value	Name	Type	Definition
GO:0043154	0.0002980689	negative regulation of caspase activity	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of caspase activity.
GO:0005881	0.0002980689	cytoplasmic microtubule	cellular_component	Any microtubule in the cytoplasm of a cell.
GO:0007051	0.0004470748	spindle organization	biological_process	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the spindle, the array of microtubules and associated molecules that forms between opposite poles of a eukaryotic cell during DNA segregation and serves to move the duplicated chromosomes apart.
GO:0031536	0.0004470748	positive regulation of exit from mitosis	biological_process	Any process that activates or increases the rate of progression from anaphase/telophase (high mitotic CDK activity) to G1 (low mitotic CDK activity).
GO:0031577	0.0002980689	spindle checkpoint	biological_process	A cell cycle checkpoint that delays the metaphase/anaphase transition until the spindle is correctly assembled and oriented, and chromosomes are attached to the spindle.
GO:0000910	0.001489583	cytokinesis	biological_process	A cellular process resulting in the division of the cytoplasm of a cell and its separation into two daughter cells. Cytokinesis usually occurs after growth, replication, and segregation of cellular components.
GO:0008017	0.001042908	microtubule binding	molecular_function	Interacting selectively and non-covalently with microtubules, filaments composed of tubulin monomers.
GO:0008536	0.0002980689	Ran GTPase binding	molecular_function	Interacting selectively and non-covalently with Ran, a conserved Ras-like GTP-binding protein, implicated in nucleocytoplasmic transport, cell cycle progression, spindle assembly, nuclear organization and nuclear envelope (NE) assembly.
GO:0000922	0.001489583	spindle pole	cellular_component	Either of the ends of a spindle, where spindle microtubules are organized; usually contains a microtubule organizing center and accessory molecules, spindle microtubules and astral microtubules.
GO:0016585	0.0002980689	chromatin remodeling complex	cellular_component	Any complex that mediates dynamic changes in eukaryotic chromatin.
GO:0043027	0.0004470748	caspase inhibitor activity	molecular_function	Stops, prevents or reduces the activity of a caspase, any of a group of cysteine proteases involved in apoptosis.
GO:0051087	0.001489583	chaperone binding	molecular_function	Interacting selectively and non-covalently with a chaperone protein, a class of proteins that bind to nascent or unfolded polypeptides and ensure correct folding or transport.
GO:0051303	0.0002980689	establishment of chromosome localization	biological_process	The directed movement of a chromosome to a specific location.
GO:0032133	0.0008939784	chromosome passenger complex	cellular_component	A eukaryotically conserved protein complex that localizes to kinetochores in early mitosis, the spindle mid-zone in anaphase B and to the telophase midbody. It has been proposed that the passenger complex coordinates various events based on its location to different structures during the course of mitosis. Complex members include the BIR-domain-containing protein Survivin, Aurora B kinase, INCENP and Borealin.
GO:0030496	1.046590e-06	midbody	cellular_component	A thin cytoplasmic bridge formed between daughter cells at the end of cytokinesis. The midbody forms where the contractile ring constricts, and may persist for some time before finally breaking to complete cytokinesis.
GO:0015631	0.0002980689	tubulin binding	molecular_function	Interacting selectively and non-covalently with monomeric or multimeric forms of tubulin, including microtubules.
GO:0005829	0.003411766	cytosol	cellular_component	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
GO:0008270	0.003274572	zinc ion binding	molecular_function	Interacting selectively and non-covalently with zinc (Zn) ions.
GO:0048037	0.0002980689	cofactor binding	molecular_function	Interacting selectively and non-covalently with a cofactor, a substance that is required for the activity of an enzyme or other protein. Cofactors may be inorganic, such as the metal atoms zinc, iron, and copper in certain forms, or organic, in which case they are referred to as coenzymes. Cofactors may either be bound tightly to active sites or bind loosely with the substrate.
GO:0005876	8.358707e-13	spindle microtubule	cellular_component	Any microtubule that is part of a mitotic or meiotic spindle; anchored at one spindle pole.
GO:0006916	3.821821e-05	anti-apoptosis	biological_process	A process which directly inhibits any of the steps required for cell death by apoptosis.
GO:0045931	0.0004470748	positive regulation of mitotic cell cycle	biological_process	Any process that activates or increases the rate or extent of progression through the mitotic cell cycle.
GO:0000775	0.002233661	chromosome, centromeric region	cellular_component	The region of a chromosome that includes the centromeric DNA and associated proteins. In monocentric chromosomes, this region corresponds to a single area of the chromosome, whereas in holocentric chromosomes, it is evenly distributed along the chromosome.
GO:0000228	0.0005960617	nuclear chromosome	cellular_component	A chromosome found in the nucleus of a eukaryotic cell.
GO:0005814	0.0004470748	centriole	cellular_component	A cellular organelle, found close to the nucleus in many eukaryotic cells, consisting of a small cylinder with microtubular walls, 300-500 nm long and 150-250 nm in diameter. It contains nine short, parallel, peripheral microtubular fibrils, each fibril consisting of one complete microtubule fused to two incomplete microtubules. Cells usually have two centrioles, lying at right angles to each other. At division, each pair of centrioles generates another pair and the twin pairs form the pole of the mitotic spindle.
GO:0051301	0.0002980689	cell division	biological_process	The process resulting in the physical partitioning and separation of a cell into daughter cells.
GO:0031021	0.0002980689	interphase microtubule organizing center	cellular_component	A microtubule organizing center found in interphase cells, which organize a longitudinal array of three to five MT bundles from the nuclear envelope during interphase. Each MT bundle is composed of two to seven MTs arranged in an antiparallel configuration, with the dynamic MT plus ends extending toward the cell tips and stable minus ends near the nucleus.
GO:0000086	0.001042908	G2/M transition of mitotic cell cycle	biological_process	Progression from G2 phase to M phase of the mitotic cell cycle.
GO:0031503	0.0002980689	protein complex localization	biological_process	Any process by which a protein complex is transported to, or maintained in, a specific location.
#Interactions in sub network3
Protein1	Protein2	Interaction Type
KPNA2	CSNK1A1	PPI
CDA	CDA	PPI
CDA	KPNA2	PPI
KPNA2	RECQL	PPI
#GO	P value	Name	Type	Definition
GO:0030308	0.004167104	negative regulation of cell growth	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of cell growth.
GO:0051289	0.0005960998	protein homotetramerization	biological_process	The formation of a protein homotetramer, a macromolecular structure consisting of four noncovalently associated identical subunits.
GO:0004126	0.0001703414	cytidine deaminase activity	molecular_function	Catalysis of the reaction: cytidine + H2O = uridine + NH3.
GO:0045980	0.0001703414	negative regulation of nucleotide metabolic process	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of the chemical reactions and pathways involving nucleotides.
GO:0001882	0.0001703414	nucleoside binding	molecular_function	Interacting selectively and non-covalently with a nucleoside, a compound consisting of a purine or pyrimidine nitrogenous base linked either to ribose or deoxyribose.
GO:0009972	0.0001703414	cytidine deamination	biological_process	The removal of amino group in the presence of water.
GO:0008270	0.001872559	zinc ion binding	molecular_function	Interacting selectively and non-covalently with zinc (Zn) ions.
#Interactions in sub network4
Protein1	Protein2	Interaction Type
MCM4	MCM6	PPI
MCM6	MCM6	PPI
CRLS1	MCM6	PPI
#GO	P value	Name	Type	Definition
GO:0005654	0.002324090	nucleoplasm	cellular_component	That part of the nuclear content other than the chromosomes or the nucleolus.
GO:0006260	3.156751e-05	DNA replication	biological_process	The cellular metabolic process whereby new strands of DNA are synthesized. The template for replication can either be an existing DNA molecule or RNA.
#Interactions in sub network5
Protein1	Protein2	Interaction Type
PTPRC	SKAP1	PPI
LCP2	PTPRC	PPI
CD1D	PTPRC	PPI
#GO	P value	Name	Type	Definition
GO:0050852	0.0007663977	T cell receptor signaling pathway	biological_process	A series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.
GO:0019901	0.004210342	protein kinase binding	molecular_function	Interacting selectively and non-covalently with a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
#Interactions in sub network6
Protein1	Protein2	Interaction Type
MASP1	MBL2	PPI
C2	MASP1	PPI
#GO	P value	Name	Type	Definition
GO:0001867	0.0002981007	complement activation, lectin pathway	biological_process	Any process involved in the activation of any of the steps of the lectin pathway of the complement cascade which allows for the direct killing of microbes and the regulation of other immune processes.
GO:0005576	3.293447e-05	extracellular region	cellular_component	The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
GO:0048306	0.001064441	calcium-dependent protein binding	molecular_function	Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules), in the presence of calcium.

#sub networks deregulated initially from BCLC stage B HCC

#Interactions in sub network1
Protein1	Protein2	Interaction Type
SGK	KPNA2	PPI
SETDB1	GIPC2	PPI
NMT2	TP53	PPI
TP53	IGFBP3	TRI
TK1	SETDB1	PPI
TK1	TP53	PPI
TP53	PDGFC	TRI
SETDB1	OLFML3	PPI
HSP90AB1	TP53	PPI
SETDB1	SULT1E1	PPI
TARDBP	SETDB1	PPI
ARL4A	KPNA2	PPI
PTTG1	TP53	PPI
TP53	HSP90AB1	TRI
TP53	SCAMP1	PPI
TP53	IFI16	PPI
TP53	CCNA2	PPI
S100A8	TP53	PPI
TP53	CYP3A7	TRI
TP53	FIGNL1	TRI
SMYD2	TP53	PPI
TP53	HELLS	TRI
KPNA2	TP53	PPI
RAB4A	TP53	PPI
TP53	HIGD1A	TRI
TP53	EHD3	TRI
TP53	FAS	TRI
#GO	P value	Name	Type	Definition
GO:0042771	0.003443069	DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis	biological_process	A cascade of processes induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage and resulting in the initiation of apoptosis (programmed cell death).
#Interactions in sub network2
Protein1	Protein2	Interaction Type
HMMR	TPX2	PPI
TPX2	TPX2	PPI
TPX2	AURKA	PPI
#GO	P value	Name	Type	Definition
GO:0000922	0.000638692	spindle pole	cellular_component	Either of the ends of a spindle, where spindle microtubules are organized; usually contains a microtubule organizing center and accessory molecules, spindle microtubules and astral microtubules.
GO:0015630	0.0004471129	microtubule cytoskeleton	cellular_component	The part of the cytoskeleton (the internal framework of a cell) composed of microtubules and associated proteins.
GO:0032147	0.0003832478	activation of protein kinase activity	biological_process	Any process that initiates the activity of an inactive protein kinase.
GO:0019901	6.009732e-06	protein kinase binding	molecular_function	Interacting selectively and non-covalently with a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
#Interactions in sub network3
Protein1	Protein2	Interaction Type
CDK6	TGFBR1	PPI
AR	CDK6	PPI
#GO	P value	Name	Type	Definition
GO:0005524	0.003829336	ATP binding	molecular_function	Interacting selectively and non-covalently with ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
GO:0006468	0.005571375	protein amino acid phosphorylation	biological_process	The process of introducing a phosphate group on to a protein.
#Interactions in sub network4
Protein1	Protein2	Interaction Type
CD8A	PTPRC	PPI
STAT1	INDO	TRI
FYB	LCP2	PPI
LCP2	LYN	PPI
INSR	KHDRBS1	PPI
SMAD2	INSR	PPI
MCM3	MCM7	PPI
CSF2RB	STAT1	PPI
SMAD2	SQSTM1	PPI
NR1I3	PPARGC1A	PPI
MAD2L1	CSF2RB	PPI
HRAS	SOS1	PPI
CDKN2A	GMNN	PPI
LYN	EPOR	PPI
SMAD2	ESR1	PPI
NR1I3	PPARBP	PPI
MCM5	MCM7	PPI
LYN	FCGR2B	PPI
CSF2RB	PRKCB1	PPI
ZMYND8	PRKCB1	PPI
MCM3	MCM6	PPI
ESR1	JUNB	PPI
MAD2L1	MBL2	PPI
LYN	LYN	PPI
PPARBP	ESR1	PPI
PPP2R1B	MCM3	PPI
MAD2L1	INSR	PPI
PRMT2	ESR1	PPI
PPARBP	PPARA	PPI
PPARGC1A	ESR1	PPI
PTPRC	LYN	PPI
SKAP1	LYN	PPI
SMURF2	SMAD2	PPI
CSE1L	CDH1	PPI
MCM3	STAT1	PPI
CSE1L	STAT1	PPI
SMAD2	SMAD2	PPI
PRMT2	PRMT2	PPI
LYN	CSF2RB	PPI
INSR	PTK2	PPI
GMNN	MCM6	PPI
YWHAB	INSR	PPI
CSF2RB	CSF2RB	PPI
MCM5	MCM3	PPI
SPTAN1	PRKCB1	PPI
CD24	LYN	PPI
HRAS	INSR	PPI
HRAS	AGTR1	PPI
#GO	P value	Name	Type	Definition
GO:0032444	0.006111452	activin responsive factor complex	cellular_component	A transcriptionally active complex that binds to an activin response element (ARE) in the promoter of target genes, and is composed of two SMAD2 proteins, one SMAD4 protein and a Forkhead activin signal transducer (FAST) transcription factor.
GO:0006260	1.976117e-05	DNA replication	biological_process	The cellular metabolic process whereby new strands of DNA are synthesized. The template for replication can either be an existing DNA molecule or RNA.
GO:0005160	0.006111452	transforming growth factor beta receptor binding	molecular_function	Interacting selectively and non-covalently with the transforming growth factor beta receptor.
GO:0070410	0.007126466	co-SMAD binding	molecular_function	Interacting selectively and non-covalently with a common mediator SMAD signaling protein.
GO:0005515	1.393031e-06	protein binding	molecular_function	Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
GO:0005654	5.43371e-05	nucleoplasm	cellular_component	That part of the nuclear content other than the chromosomes or the nucleolus.
GO:0007182	0.002041228	common-partner SMAD protein phosphorylation	biological_process	The process of introducing a phosphate group on to a common-partner SMAD protein. A common partner SMAD protein binds to pathway-restricted SMAD proteins forming a complex that translocates to the nucleus.
GO:0070304	0.002041228	positive regulation of stress-activated protein kinase signaling pathway	biological_process	Any process that activates or increases the frequency, rate or extent of signaling via the stress-activated protein kinase signaling pathway.
GO:0045121	0.0003266701	membrane raft	cellular_component	Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions.
GO:0030618	0.004078376	transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity	molecular_function	A TGF-beta cytoplasmic mediator that is phosphorylated by a TGFbeta receptor and complexes with a common-partner mediator. The- heterocomplex translocates to the nucleus to regulate transcription.
GO:0051272	0.005095423	positive regulation of cellular component movement	biological_process	Any process that activates or increases the frequency, rate or extent of the movement of a cellular component.
GO:0070723	0.009153449	response to cholesterol	biological_process	A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cholesterol stimulus.
GO:0007352	0.002041228	zygotic specification of dorsal/ventral axis	biological_process	The specification of the dorsal/ventral axis of the embryo, through the products of genes expressed in the zygote.
#Interactions in sub network5
Protein1	Protein2	Interaction Type
C1QB	C1QA	PPI
C1R	C1QB	PPI
C1QC	C1QA	PPI
C1QC	C1QB	PPI
#GO	P value	Name	Type	Definition
GO:0005576	1.100744e-09	extracellular region	cellular_component	The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
#Interactions in sub network6
Protein1	Protein2	Interaction Type
GPLD1	APOA1	PPI
EGR1	APOA1	TRI
APOA1	APOF	PPI
APOA1	APOA1	PPI
APOA1	CETP	PPI
#GO	P value	Name	Type	Definition
GO:0031410	0.001064237	cytoplasmic vesicle	cellular_component	A vesicle formed of membrane or protein, found in the cytoplasm of a cell.
GO:0050713	0.00021292	negative regulation of interleukin-1 beta secretion	biological_process	Any process that stops, prevents or reduces the frequency, rate or extent of the regulated release of interleukin-1 beta from a cell or group of cells.
GO:0033344	0.001064237	cholesterol efflux	biological_process	The directed movement of cholesterol, cholest-5-en-3-beta-ol, out of a cell or organelle.
GO:0030301	3.263489e-07	cholesterol transport	biological_process	The directed movement of cholesterol, cholest-5-en-3-beta-ol, into, out of, within or between cells by means of some external agent such as a transporter or pore.
GO:0034191	0.00021292	apolipoprotein A-I receptor binding	molecular_function	Interacting selectively and non-covalently with an apolipoprotein A-I receptor.
GO:0034361	0.0009578543	very-low-density lipoprotein particle	cellular_component	A triglyceride-rich lipoprotein particle that is typically composed of APOB100, APOE and APOCs and has a density of about 1.006 g/ml and a diameter of between 20-80 nm. It is found in blood and transports endogenous products (newly synthesized cholesterol and triglycerides) from the liver.
GO:0051345	0.00021292	positive regulation of hydrolase activity	biological_process	Any process that activates or increases the frequency, rate or extent of hydrolase activity, the catalysis of the hydrolysis of various bonds.
GO:0030141	0.0004258037	secretory granule	cellular_component	A small subcellular vesicle, surrounded by a membrane, that is formed from the Golgi apparatus and contains a highly concentrated protein destined for secretion. Secretory granules move towards the periphery of the cell, their membranes fuse with the cell membrane, and their protein load is exteriorized. Processing of the contained protein may take place in secretory granules.
GO:0030139	0.000532232	endocytic vesicle	cellular_component	A membrane-bounded intracellular vesicle formed by invagination of the plasma membrane around an extracellular substance.
GO:0033700	0.0009578543	phospholipid efflux	biological_process	The directed movement of a phospholipid out of a cell or organelle.
GO:0043691	0.0009578543	reverse cholesterol transport	biological_process	The directed movement of peripheral cell cholesterol, cholest-5-en-3-beta-ol, towards the liver for catabolism.
GO:0006656	0.0004258037	phosphatidylcholine biosynthetic process	biological_process	The chemical reactions and pathways resulting in the formation of phosphatidylcholines, any of a class of glycerophospholipids in which the phosphatidyl group is esterified to the hydroxyl group of choline.
GO:0005788	0.001170611	endoplasmic reticulum lumen	cellular_component	The volume enclosed by the membranes of the endoplasmic reticulum.
GO:0008203	4.985461e-07	cholesterol metabolic process	biological_process	The chemical reactions and pathways involving cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones. It is a component of the plasma membrane lipid bilayer and of plasma lipoproteins and can be found in all animal tissues.
GO:0010903	0.0003193664	negative regulation of very-low-density lipoprotein particle remodeling	biological_process	Any process that decreases the rate, frequency or extent of very-low-density lipoprotein particle remodeling. Very-low-density lipoprotein particle remodeling is the acquisition, loss or modification of a protein or lipid within a very-low-density lipoprotein particle, including the hydrolysis of triglyceride by hepatic lipase or lipoprotein lipase and the subsequent loss of free fatty acid.
GO:0070653	0.0003193664	high-density lipoprotein receptor binding	molecular_function	Interacting selectively and non-covalently with a high-density lipoprotein receptor.
GO:0015485	1.359961e-07	cholesterol binding	molecular_function	Interacting selectively and non-covalently with cholesterol (cholest-5-en-3-beta-ol); the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones.
GO:0034190	0.0004258037	apolipoprotein receptor binding	molecular_function	Interacting selectively and non-covalently with an apolipoprotein receptor.
GO:0034364	7.069688e-07	high-density lipoprotein particle	cellular_component	A lipoprotein particle with a high density (typically 1.063-1.21 g/ml) and a diameter of 5-10 nm that contains APOAs and may contain APOCs and APOE; found in blood and carries lipids from body tissues to the liver as part of the reverse cholesterol transport process.
GO:0002740	0.000532232	negative regulation of cytokine secretion during immune response	biological_process	Any process that stops, prevents, or reduces the frequency, rate, or extent of cytokine secretion during immune response.
GO:0005576	0.0003255601	extracellular region	cellular_component	The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
GO:0070508	0.00021292	cholesterol import	biological_process	The directed movement of cholesterol into a cell or organelle.
GO:0042632	1.549497e-06	cholesterol homeostasis	biological_process	Any process involved in the maintenance of an internal steady-state of cholesterol within an organism or cell.
GO:0032488	0.0004258037	Cdc42 protein signal transduction	biological_process	A series of molecular signals within the cell that are mediated by the Cdc42 protein switching to a GTP-bound active state.
GO:0001540	0.0007450613	beta-amyloid binding	molecular_function	Interacting selectively and non-covalently with beta-amyloid peptide/protein and/or its precursor.
GO:0034366	0.0006386511	spherical high-density lipoprotein particle	cellular_component	A mature high-density lipoprotein (HDL) particle, converted from discoidal HDL particles following the esterification of cholesterol in the particle by phosphatidylcholine-sterol O-acyltransferase (lecithin cholesterol acyltransferase; LCAT).
GO:0017127	4.985461e-07	cholesterol transporter activity	molecular_function	Enables the directed movement of cholesterol into, out of, within or between cells. Cholesterol is the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones.
GO:0034380	0.000532232	high-density lipoprotein particle assembly	biological_process	The aggregation and arrangement of proteins and lipids to form a high-density lipoprotein particle.
GO:0005543	0.001170611	phospholipid binding	molecular_function	Interacting selectively and non-covalently with phospholipids, a class of lipids containing phosphoric acid as a mono- or diester.
GO:0060228	0.000532232	phosphatidylcholine-sterol O-acyltransferase activator activity	molecular_function	Increases the activity of phosphatidylcholine-sterol O-acyltransferase, an enzyme that converts cholesterol and phosphatidylcholine (lecithins) to cholesteryl esters and lyso-phosphatidylcholines.
GO:0050821	0.0008514623	protein stabilization	biological_process	Any process involved in maintaining the structure and integrity of a protein and preventing it from degradation or aggregation.
GO:0019899	0.009122865	enzyme binding	molecular_function	Interacting selectively and non-covalently with any enzyme.
GO:0010873	0.0007450613	positive regulation of cholesterol esterification	biological_process	Any process that increases the frequency, rate or extent of cholesterol esterification. Cholesterol esterification is the lipid modification process in which a sterol ester is formed by the combination of a carboxylic acid (often a fatty acid) and cholesterol. In the blood this process is associated with the conversion of free cholesterol into cholesteryl ester, which is then sequestered into the core of a lipoprotein particle.

#sub networks deregulated initially from BCLC stage C HCC

#Interactions in sub network1
Protein1	Protein2	Interaction Type
GGA1	AP1GBP1	PPI
GGA3	AP1GBP1	PPI
GGA3	GGA3	PPI
#GO	P value	Name	Type	Definition
GO:0030306	0.00031938	ADP-ribosylation factor binding	molecular_function	Interacting selectively and non-covalently with ARF, ADP-ribosylation factor, a small monomeric cytosolic GTPase that, when bound to GTP, binds to the membranes of cells.
GO:0005802	0.0007025462	trans-Golgi network	cellular_component	The network of interconnected tubular and cisternal structures located at the side of the Golgi apparatus distal to the endoplasmic reticulum, from which secretory vesicles emerge. The trans-Golgi network is important in the later stages of protein secretion where it is thought to play a key role in the sorting and targeting of secreted proteins to the correct destination.
#Interactions in sub network2
Protein1	Protein2	Interaction Type
BMP2	ASCL1	PPI
BMP2	BMP2	PPI
GREM2	BMP2	PPI
BMPER	BMP2	PPI
#GO	P value	Name	Type	Definition
GO:0001649	0.0004258128	osteoblast differentiation	biological_process	The process whereby a relatively unspecialized cell acquires the specialized features of an osteoblast, the mesodermal cell that gives rise to bone.
GO:0045786	0.001191933	negative regulation of cell cycle	biological_process	Any process that stops, prevents or reduces the rate or extent of progression through the cell cycle.
GO:0060317	0.0004258128	cardiac epithelial to mesenchymal transition	biological_process	A transition where a cardiac epithelial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell.
GO:0035051	0.0001703414	cardiac cell differentiation	biological_process	The process whereby a relatively unspecialized cell acquires the specialized structural and/or functional features of a cell that will form part of the cardiac organ of an individual.
GO:0016566	0.001021722	specific transcriptional repressor activity	molecular_function	Any activity that stops or downregulates transcription of specific genes or sets of genes.
GO:0045778	0.0004258128	positive regulation of ossification	biological_process	Any process that activates or increases the frequency, rate or extent of bone formation.
GO:0010862	0.002127704	positive regulation of pathway-restricted SMAD protein phosphorylation	biological_process	Any process that increases the rate, frequency or extent of SMAD protein nuclear translocation. SMAD protein nuclear translocation is the vectorial transfer of a SMAD proteins from the cytoplasm into the nucleus, through the nuclear pore. Pathway-restricted SMAD proteins and common-partner SMAD proteins are involved in the transforming growth factor beta receptor signaling pathways.
GO:0001934	0.001277030	positive regulation of protein amino acid phosphorylation	biological_process	Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
GO:0005576	0.0001960897	extracellular region	cellular_component	The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
GO:0001938	0.000766365	positive regulation of endothelial cell proliferation	biological_process	Any process that activates or increases the rate or extent of endothelial cell proliferation.
GO:0001837	0.0004258128	epithelial to mesenchymal transition	biological_process	A transition where an epithelial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell.
GO:0032582	1.958371e-07	negative regulation of gene-specific transcription	biological_process	Any process that stops, prevents or reduces the DNA-dependent transcription of a specific gene or genes.
GO:0045941	0.009505656	positive regulation of transcription	biological_process	Any cellular process that activates or increases the frequency, rate or extent of transcription.
GO:0030509	1.237139e-05	BMP signaling pathway	biological_process	A series of molecular signals generated as a consequence of any member of the BMP (bone morphogenetic protein) family binding to a cell surface receptor.
GO:0016563	0.00722034	transcription activator activity	molecular_function	Any transcription regulator activity required for initiation or upregulation of transcription.
GO:0045669	0.0023828	positive regulation of osteoblast differentiation	biological_process	Any process that activates or increases the frequency, rate or extent of osteoblast differentiation.
GO:0010628	0.0008514895	positive regulation of gene expression	biological_process	Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA (for protein-coding genes) and the translation of that mRNA into protein. Some protein processing events may be included when they are required to form an active form of a product from an inactive precursor form.
GO:0060395	0.001532290	SMAD protein signal transduction	biological_process	The cascade of processes by which a signal interacts with a receptor, causing a change in the activity of a SMAD protein, and ultimately effecting a change in the functioning of the cell.
GO:0030501	0.002467821	positive regulation of bone mineralization	biological_process	Any process that activates or increases the frequency, rate or extent of bone mineralization.
GO:0060389	0.001617365	pathway-restricted SMAD protein phosphorylation	biological_process	The process of introducing a phosphate group on to a pathway restricted SMAD protein. A pathway restricted SMAD protein is an effector protein that acts directly downstream of the transforming growth factor family receptor.
GO:0046332	0.002977834	SMAD binding	molecular_function	Interacting selectively and non-covalently with a SMAD signaling protein.
GO:0045449	0.0023828	regulation of transcription	biological_process	Any process that modulates the frequency, rate or extent of the synthesis of either RNA on a template of DNA or DNA on a template of RNA.
GO:0048762	0.0001703414	mesenchymal cell differentiation	biological_process	The process whereby a relatively unspecialized cell acquires specialized features of a mesenchymal cell. A mesenchymal cell is a loosely associated cell that is part of the connective tissue in an organism. Mesenchymal cells give rise to more mature connective tissue cell types.
#Interactions in sub network3
Protein1	Protein2	Interaction Type
SNRPA	SNRPA	PPI
SMAD5	BCAT1	PPI
SMAD5	SNRPA	PPI
#GO	P value	Name	Type	Definition
GO:0005681	0.000638692	spliceosomal complex	cellular_component	Any of a series of ribonucleoprotein complexes that contain RNA and small nuclear ribonucleoproteins (snRNPs), and are formed sequentially during the splicing of a messenger RNA primary transcript to excise an intron.
GO:0008380	0.008726436	RNA splicing	biological_process	The process of removing sections of the primary RNA transcript to remove sequences not present in the mature form of the RNA and joining the remaining sections to form the mature form of the RNA.
#Interactions in sub network4
Protein1	Protein2	Interaction Type
TJP2	CLDN1	PPI
MPDZ	CLDN1	PPI
MPDZ	MPDZ	PPI
#GO	P value	Name	Type	Definition
GO:0008022	0.006183841	protein C-terminus binding	molecular_function	Interacting selectively and non-covalently with a protein C-terminus, the end of any peptide chain at which the 1-carboxy function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue.
#Interactions in sub network5
Protein1	Protein2	Interaction Type
SMARCE1	ESR1	PPI
NCOA6	PRKDC	PPI
SHBG	SORD	PPI
ATR	NBN	PPI
PIAS3	NCOA2	PPI
LMNB1	LMNA	PPI
PLCG1	LIFR	PPI
SYT9	SYNCRIP	PPI
AR	CDC25B	PPI
PRKAR2A	MAP2	PPI
CDC7	CDKN2A	PPI
MST1	MST1	PPI
SFN	C8orf32	PPI
GBP2	PAFAH1B3	PPI
KPNA2	ITK	PPI
NDRG1	EIF3S6	PPI
WASF1	GRB2	PPI
CLEC3B	CLEC3B	PPI
TTF2	MATR3	PPI
NCOA7	ESR1	PPI
REPS2	CDK5RAP2	PPI
BCOR	MLLT3	PPI
PTMA	HSPA1A	PPI
MAPK1	TCF3	PPI
S100A10	SETDB1	PPI
MMP2	IGFBP3	PPI
CDC2	LMNB1	PPI
SYNCRIP	PABPC1	PPI
PTK2	LYN	PPI
F2	SERPINE1	PPI
ATXN1	ZHX2	PPI
PTPN1	ESR1	PPI
TP53	LASP1	TRI
MLLT3	MCM6	PPI
ITGA2	COL1A2	PPI
ATXN1	BTG3	PPI
PPARA	PRKCD	PPI
CDC5L	MCM3	PPI
HDAC2	CDC20	PPI
OPTN	FOS	PPI
NR1I2	PPARGC1A	PPI
YWHAB	KIF5B	PPI
CTLA4	CTLA4	PPI
COL4A5	FN1	PPI
TM4SF1	TUBA4A	PPI
HSPB1	TGFB1I1	PPI
F12	APOH	PPI
KITLG	EPOR	PPI
SNRPD2	SNRPD2	PPI
PRKCA	ADD3	PPI
ANXA2	CDC42	PPI
DNMT1	DNMT1	PPI
RAD1	FEN1	PPI
KRT19	FANCG	PPI
BLM	FEN1	PPI
SERPINA5	KLKB1	PPI
HDAC2	PTMA	PPI
BARD1	MDC1	PPI
MLLT3	MLLT3	PPI
C1S	C1QA	PPI
PPARBP	TP53	PPI
ESR1	TRIM59	PPI
FOXM1	IGFBP1	TRI
CLEC3B	PLG	PPI
PRKCD	YWHAZ	PPI
HMGA1	IGFBP1	TRI
CDC7	MCM7	PPI
TP53	TAP1	TRI
PDLIM5	TRIM39	PPI
RRAS2	PTPN1	PPI
BIRC5	CDK4	PPI
PRKCD	PLCB1	PPI
SMAD2	DYNC1H1	PPI
GZMA	HMGB2	PPI
FBN1	DCN	PPI
CKAP5	AURKA	PPI
TAF6	TAF4	PPI
SMAD2	KHDRBS1	PPI
INSR	ADRB2	PPI
SERPINC1	SERPINC1	PPI
REPS2	GRB2	PPI
EED	EZH2	PPI
KITLG	KIT	PPI
ESR1	UBE2I	PPI
ANPEP	ADH1B	TRI
PLK1	TUBG1	PPI
TP53	WNK1	TRI
SETDB1	RIF1	PPI
DBF4	MCM7	PPI
PAFAH1B3	SETDB1	PPI
ETV4	IL8	TRI
YWHAG	LIMA1	PPI
ETV4	FOS	TRI
UBE2I	CBX4	PPI
PPARBP	AR	PPI
ORC6L	MCM6	PPI
S100A8	RAB17	PPI
MAP3K5	MAP3K5	PPI
HSPA4	CDC73	PPI
TRIM24	TRIM28	PPI
AR	IFI16	PPI
BCR	PLCG1	PPI
SLC16A3	BSG	PPI
RAN	RAN	PPI
PEBP1	PEBP1	PPI
NCOA6	ESR1	PPI
PPARGC1A	RXRA	PPI
HMGA1	JUN	PPI
AZGP1	ITGAV	PPI
LMNA	UBE2I	PPI
NCOA3	NR1I2	PPI
CCL21	UBQLN4	PPI
TAF1A	TP53	PPI
FN1	F13A1	PPI
PLK1	BUB1	PPI
NCOA3	JUN	PPI
PRKCA	PRKCA	PPI
KHDRBS1	PLCG1	PPI
PRKCE	PRKCE	PPI
HGS	MAP3K7	PPI
ANPEP	CRP	TRI
F9	F7	PPI
PRKAG2	PRKAB1	PPI
PER1	CSNK1D	PPI
CSNK1D	TP53	PPI
SMARCA2	KHDRBS1	PPI
HDAC2	DNMT1	PPI
VIPR1	PTMA	PPI
TPM2	JUN	PPI
KNG1	KNG1	PPI
CENPF	SNAP25	PPI
TRAF5	CD27	PPI
SIP1	SNRPD2	PPI
CHEK1	TP53	PPI
SFN	PLEKHF2	PPI
F8	F2	PPI
MCM5	MCM2	PPI
F7	F7	PPI
RAD54B	UBE2I	PPI
GNE	RIF1	PPI
PLAT	SERPINI1	PPI
CSE1L	RAN	PPI
CBX1	TRIM24	PPI
PAK1	MAP2K1	PPI
TCERG1	HSPA1A	PPI
CDKN2A	MCM2	PPI
SF3B4	TCERG1	PPI
GRB2	SH3KBP1	PPI
TRIM39	TRIM39	PPI
NME1	TERF1	PPI
BIN1	DDEF2	PPI
MCM6	MCM2	PPI
DVL3	PPM1A	PPI
MINK1	YWHAB	PPI
TP53	RRM2B	TRI
MATN2	COL4A5	PPI
PLK1	MCM7	PPI
VIM	TRIM28	PPI
KPNA2	CASP2	PPI
ORC6L	MCM7	PPI
PSME3	KIAA1267	PPI
NCOA6	NCOA6	PPI
PCNA	RFC3	PPI
ALDOA	ALDOA	PPI
SERPING1	SELE	PPI
NME1	KSR1	PPI
YWHAZ	PRKCA	PPI
PRKCA	MARCKS	PPI
PIK3R1	IFNAR1	PPI
TBCB	TUBA4A	PPI
ESR1	CDC25B	PPI
ALS2CR8	CDKN2A	PPI
STXBP6	SNAP25	PPI
ESR1	TUBA1B	PPI
SMAD2	RXRA	PPI
KIF23	PLK1	PPI
CDC2	PTCH1	PPI
DBF4	CDC7	PPI
YWHAG	PCTK1	PPI
MMP9	TFPI	PPI
AATF	CHEK1	PPI
AGR2	UBQLN4	PPI
SMURF2	ACBD3	PPI
SLC16A1	BSG	PPI
KLKB1	KNG1	PPI
LMAN1	F8	PPI
RPS6KA3	RPS6KA3	PPI
PRKCA	PLD1	PPI
GRB2	ESR1	PPI
CLEC3B	PLAT	PPI
STIP1	HSPA1A	PPI
SOS1	GRB2	PPI
UBE2I	PRPF40A	PPI
UBE2I	DNMT3A	PPI
ANXA2	CTSB	PPI
MAPKAPK2	HSPB1	PPI
FOXM1	APOB	TRI
FOXM1	G6PC	TRI
RALBP1	RALA	PPI
MCM3	PLK1	PPI
MDC1	H2AFX	PPI
MCM10	CDC7	PPI
LYN	CTLA4	PPI
YWHAB	HSPA1B	PPI
DOCK8	CDC42	PPI
SHC1	NGFR	PPI
SKAP1	LCK	PPI
PCNA	RFC4	PPI
PCTK1	PCTK1	PPI
SHC1	PAK1	PPI
FBXO5	CDC20	PPI
BUB1B	CENPE	PPI
TIAM1	NME1	PPI
HIST1H2BG	PTMA	PPI
MCM3	MCM2	PPI
PPARA	ACADM	TRI
MCM10	CDC45L	PPI
GADD45G	RXRA	PPI
F2	F2RL1	PPI
IRAK1	HRAS	PPI
CDC7	MCM2	PPI
CDC2	NES	PPI
HSPB1	DAXX	PPI
SMARCA4	HSF1	PPI
YWHAG	CHEK1	PPI
TOLLIP	TOLLIP	PPI
CDKN2C	CDK4	PPI
SMARCA4	SMARCE1	PPI
PTMA	CDK4	PPI
RAP1GAP	RAP1GAP	PPI
PLG	ANXA2	PPI
CHEK1	CDC25C	PPI
RIPK2	UBE2I	PPI
PAFAH1B3	PAFAH1B3	PPI
HMGA1	NFYA	PPI
HSPA1A	NQO1	PPI
MDC1	MDC1	PPI
CENPF	CENPE	PPI
TGFB1	FNTA	PPI
ESR1	F12	TRI
TOLLIP	IL1RAP	PPI
TGFB1	SPARC	PPI
MCM5	ORC6L	PPI
GADD45G	ESR1	PPI
PCNA	MSH2	PPI
LEF1	U2AF2	TRI
NFYA	KPNB1	PPI
LYN	HCLS1	PPI
HDAC2	TOP2A	PPI
ALB	F7	PPI
PTK2	SELE	PPI
CD36	YES1	PPI
HSPA4	NR3C2	PPI
LCN2	MMP9	PPI
NR3C2	TRIM24	PPI
PTMA	PCNA	PPI
CDK5	MAP2K1	PPI
RAN	SMURF2	PPI
ANPEP	FOS	TRI
CDC20	TGFBR1	PPI
AR	F9	TRI
PRKCA	SLC1A1	PPI
TRIP13	C8orf32	PPI
AP2B1	BUB1	PPI
TIAM1	HRAS	PPI
NCAPG	HSF2	PPI
PPIA	BSG	PPI
LCP2	VAV3	PPI
KITLG	KITLG	PPI
AURKB	CENPA	PPI
EGR1	TGFB1	TRI
SMAD2	NCOA6	PPI
C6	F2	PPI
TMF1	AR	PPI
MEP1A	FN1	PPI
SYNE1	SYNE1	PPI
NR1I2	CYP3A4	TRI
POLA1	CDC2	PPI
HDAC2	CDH1	PPI
CDK4	RFC4	PPI
PRKCA	SNAP25	PPI
PAK1	COL1A1	PPI
PLG	SERPINC1	PPI
KNG1	PLG	PPI
PLK1	PRC1	PPI
SMAD2	HGS	PPI
CFI	CFH	PPI
SMAD2	KPNB1	PPI
PLCG1	CTSS	PPI
WASF2	GRB2	PPI
HRAS	GRB2	PPI
RXRA	ACADM	TRI
CBL	YWHAZ	PPI
IGF2	IGFBP4	PPI
MCM10	MCM4	PPI
MMP9	CXCL5	PPI
FZD7	UBQLN4	PPI
F11	KNG1	PPI
RNPS1	UBQLN4	PPI
YWHAZ	ENO1	PPI
SORBS2	PKM2	PPI
PCNA	PCNA	PPI
PTK2	GRB2	PPI
SMC4	NCAPD2	PPI
AKAP12	ADRB2	PPI
ITGA2	MMP1	PPI
UBQLN4	MIF4GD	PPI
PAK1	ESR1	PPI
GADD45A	CDC2	PPI
PABPC1	GSPT1	PPI
CBX1	CBX5	PPI
ATR	CHEK1	PPI
YWHAZ	VIM	PPI
TP53RK	TP53	PPI
INSR	SHC1	PPI
MCM10	CDC6	PPI
SHC1	RET	PPI
LCK	MED28	PPI
PTPRC	GRB2	PPI
SOCS7	GRB2	PPI
PRKCA	INSR	PPI
SHC1	MME	PPI
ESR1	U2AF2	TRI
TAF6	SH3KBP1	PPI
TFPI	MMP12	PPI
IGFBP3	F2	PPI
KHDRBS1	GRB2	PPI
PRKCB1	ANXA2	PPI
SCG5	UBQLN4	PPI
GNAO1	RGS10	PPI
CDC2	FEN1	PPI
IGF1	IGFBP1	PPI
SMAD2	MAPK9	PPI
TP53	MSH2	TRI
NOV	FN1	PPI
LYN	MME	PPI
DDEF2	RAN	PPI
TCERG1	SETDB1	PPI
NR2F1	F9	TRI
LYN	CDC2	PPI
AKAP12	PRKCA	PPI
PRKCA	SHC1	PPI
MMP1	IGFBP3	PPI
RAN	PTMA	PPI
FOXM1	CYP7A1	TRI
CCNB2	MCM2	PPI
PRKDC	PRKCD	PPI
ENO1	CXCL2	PPI
CDCA8	CDCA8	PPI
C4BPB	PROS1	PPI
PPARBP	MED12	PPI
F2	HGFAC	PPI
PRKCD	INSR	PPI
BCL2A1	BAX	PPI
COL4A2	SAA1	PPI
HSPA2	CDC2	PPI
GHR	GRB2	PPI
JUN	VIM	TRI
MELK	LMNB1	PPI
RBP1	HDAC2	PPI
SFN	MAP3K5	PPI
OSBPL3	YWHAG	PPI
RAB17	SMURF2	PPI
NFYA	CDC2	TRI
TP53	NCAPD2	TRI
PABPC1	PCBP2	PPI
SERPINB9	SETDB1	PPI
FN1	C1QA	PPI
ZFPM2	UBQLN4	PPI
ITK	GRB2	PPI
AR	ESR1	PPI
NR3C2	PIAS3	PPI
SAP30	HIST2H2BE	PPI
CBL	LTK	PPI
CD8A	LCK	PPI
MATN2	FN1	PPI
ANXA2	GRB2	PPI
SETDB1	TOLLIP	PPI
GRK5	ADRB2	PPI
HIST2H2BE	PTMA	PPI
CSNK1D	CDK5	PPI
PABPC1	PABPC1	PPI
PLP2	SHBG	PPI
EED	HDAC2	PPI
GRB2	GRB2	PPI
ATXN1	YWHAZ	PPI
MCM4	ORC6L	PPI
BCOR	CPNE2	PPI
CENPJ	YWHAZ	PPI
TP53	CDC25C	TRI
FNTA	PTP4A3	PPI
CDK6	MCM2	PPI
SOCS7	PLCG1	PPI
CBX3	TRIM28	PPI
RALA	PPP2R1B	PPI
NR1H4	RXRA	PPI
NCOA3	PSME3	PPI
YWHAZ	HMGN1	PPI
HSPH1	CFL1	PPI
IRAK1	RIPK2	PPI
TP53	NFYA	PPI
AR	CCNE1	PPI
ORC6L	CDC6	PPI
NOV	IGF2	PPI
CDKN2A	CDK4	PPI
PLK1	MCM2	PPI
TOPBP1	TOPBP1	PPI
CDK6	PCNA	PPI
RIPK2	NGFR	PPI
CHTF18	RFC4	PPI
SERPING1	MASP1	PPI
PRKCA	KIT	PPI
CEP55	CDC2	PPI
TRIP13	PLSCR4	PPI
SERPING1	MASP2	PPI
TP53	METTL8	TRI
PPIA	PPIA	PPI
TP53	CYP4F2	TRI
CHEK1	CUL4A	PPI
STK39	MBP	PPI
NCOA2	AR	PPI
TAF1A	TAF1A	PPI
U2AF2	KIAA0907	PPI
SAP30	NCOR1	PPI
LCK	CD3E	PPI
TOB1	SMAD2	PPI
CDC6	MCM2	PPI
NPM1	TP53	PPI
YWHAG	DYNC1H1	PPI
WWC1	CDC73	PPI
TRIP13	STAMBPL1	PPI
PAK1	PRKCD	PPI
RASAL2	YWHAG	PPI
PLA1A	ANXA2	PPI
TP53	LAMA4	PPI
BSG	BSG	PPI
NUP62	PTMA	PPI
MVP	ESR1	PPI
HIST2H2BE	GADD45A	PPI
PIK3R1	ESR1	PPI
MLLT6	UBQLN4	PPI
ZNF295	YWHAG	PPI
MMP1	CCL2	PPI
DAXX	DNMT1	PPI
CBL	LYN	PPI
PCNA	CDC25C	PPI
IRF1	STAT1	TRI
SERPING1	C1R	PPI
RALGDS	HRAS	PPI
PTPN1	GRB2	PPI
F8	PROS1	PPI
RRM2B	TP53	PPI
KSR1	MAP2K1	PPI
ATP1A1	EZH2	PPI
CBX1	DNMT1	PPI
PTMA	CDC2	PPI
MMP12	LPA	PPI
CRLS1	MCM7	PPI
MIF	TP53	PPI
PRKCA	TOP2A	PPI
KRT19	HGS	PPI
SPRY2	GRB2	PPI
ANAPC7	CDC20	PPI
YES1	YES1	PPI
EZH2	SMS	PPI
SPC25	NDC80	PPI
TP53	SLC44A5	TRI
NFYA	CCNA2	TRI
EIF3S6	GPAA1	PPI
F5	F2	PPI
ETV4	MMP9	TRI
CDCA8	AURKB	PPI
MATN2	COL4A1	PPI
PLK1	CDC25C	PPI
MAPK9	SF3B4	PPI
CDC7	ORC6L	PPI
NEK2	MAPK1	PPI
LCK	PTK2	PPI
F2	PROZ	PPI
PAG1	LYN	PPI
BCR	BCR	PPI
NR1I2	RXRA	PPI
HSF1	HSF1	PPI
PRKCA	TP53	PPI
FOS	TGFB1	TRI
CENPJ	TUBG1	PPI
TTR	FEZ1	PPI
CEP55	PLK1	PPI
DACH1	SIX1	PPI
MAPKAPK2	SHC1	PPI
NPM1	SHC1	PPI
XPO5	RAN	PPI
TP53	DNMT1	TRI
FOS	VIM	TRI
GPSM2	GNAO1	PPI
KPNB1	CSE1L	PPI
ADAM9	ITGAV	PPI
SETDB1	TRIM28	PPI
XK	PRKCA	PPI
CDK5	NES	PPI
PRKDC	LYN	PPI
SFN	ZFP36	PPI
DAB2	GRB2	PPI
YWHAZ	PCTK1	PPI
CDK4	MCM2	PPI
ESR1	PIAS3	PPI
MCM4	MCM7	PPI
ADCY7	PRKCD	PPI
PPARA	APOC3	TRI
F2	SPP1	PPI
GPSM2	HRAS	PPI
BLM	CHEK1	PPI
AURKB	NUF2	PPI
TP53	AFF3	TRI
F9	F2	PPI
DDEF2	SH3KBP1	PPI
IGFALS	IGFBP5	PPI
CDC2	RAB4A	PPI
MAP2	GRB2	PPI
HGS	UBE2I	PPI
PTPN1	LTK	PPI
RB1CC1	PTK2	PPI
HDAC2	SAP30	PPI
CBX1	TRIM28	PPI
BLM	FANCD2	PPI
MKI67	CBX3	PPI
HGS	MIF4GD	PPI
ADAM9	PRKCD	PPI
GRB2	ADA	PPI
KNG1	THBS1	PPI
MCM10	MCM6	PPI
PPM1A	PRKCD	PPI
PPIA	S100A8	PPI
PPARGC1A	PPARBP	PPI
DNMT1	EZH2	PPI
PAG1	SHC1	PPI
ITGB3BP	ESR1	PPI
MCM10	MCM3	PPI
AKAP9	CSNK1D	PPI
NDRG1	HSD17B4	PPI
CDC25B	CDC2	PPI
LCK	LCP2	PPI
GFRA1	RET	PPI
PRKCA	MBP	PPI
CDC2	FANCG	PPI
ANPEP	HPX	TRI
ANPEP	F8	TRI
RAMP3	VIPR1	PPI
TP53	SYNE1	TRI
NCOR1	RDBP	PPI
PRKCD	MBP	PPI
YWHAG	PABPC1	PPI
GADD45G	PTN	PPI
CDC6	MCM3	PPI
MMP12	F12	PPI
MCM10	CDK6	PPI
EDD1	MAPK1	PPI
TP53	SULT1E1	PPI
KLKB1	MST1	PPI
SNAP25	HGS	PPI
HIP1	HIP1	PPI
KPNB1	TERF1	PPI
FEN1	PCNA	PPI
NDRG1	PKM2	PPI
NME1	C8orf32	PPI
MELK	CDC5L	PPI
IRF1	CXCL10	TRI
THRAP4	RXRA	PPI
TP53	HSPA1A	PPI
CBX1	CBX3	PPI
CDC2	FOXM1	PPI
MCM10	MCM2	PPI
DGKZ	HRAS	PPI
ADRB2	GRB2	PPI
TRIM24	ESR1	PPI
UTP14A	GADD45G	PPI
DTNA	DMD	PPI
SOX9	MED12	PPI
F2	PROS1	PPI
ESR1	NQO1	TRI
BCL2A1	GRB2	PPI
TP53	GPHN	TRI
NQO1	TP53	PPI
HABP2	KNG1	PPI
MKI67	PRKCB1	PPI
DPP4	ADA	PPI
ASPM	PLK1	PPI
PCNA	CDK5	PPI
NR1I3	RXRA	PPI
FOXM1	APOA1	TRI
VIM	KIF15	PPI
TP53	NR1I2	TRI
PRUNE	NME1	PPI
HGS	PIK3R1	PPI
BCOR	HDAC6	PPI
FNTA	CENPF	PPI
PRKAR2B	LASP1	PPI
CFH	CRP	PPI
TP53	ENO1	TRI
PPARBP	RXRA	PPI
GPAA1	PIGU	PPI
MAPKAPK2	YWHAZ	PPI
NR2F1	APOA4	TRI
SKAP1	GRB2	PPI
PLG	HRG	PPI
DAXX	DAXX	PPI
PCNA	GADD45A	PPI
PCDH17	UBQLN4	PPI
PRKCA	PEA15	PPI
MAP3K5	TPD52L1	PPI
GHR	PIK3R1	PPI
SETDB1	DNMT3A	PPI
EED	TGS1	PPI
DACH1	UBE2I	PPI
SMARCC1	CCNE1	PPI
INSR	FABP4	PPI
FOS	ALDOA	TRI
PFTK1	YWHAB	PPI
CEP55	MAPK1	PPI
SMAD2	EDD1	PPI
SHC1	LTK	PPI
DNMT1	EED	PPI
SERPINE2	F2	PPI
RECK	MMP9	PPI
MAPK1	PLCB1	PPI
AURKA	TACC3	PPI
NDRG1	PABPC1	PPI
CKAP5	CKAP5	PPI
CDC25C	CDC2	PPI
ITGA2	COL1A1	PPI
KIT	KIT	PPI
MCM2	MCM2	PPI
IL1RAP	PIK3R1	PPI
CASP8	HIP1	PPI
TUBG1	PIK3R1	PPI
SPEN	HDAC2	PPI
NR3C2	AR	PPI
UTP14A	TP53BP2	PPI
RALBP1	REPS2	PPI
SERPINI1	PLG	PPI
DOCK8	RHOQ	PPI
LGALS4	RRAS2	PPI
TP53	TRIM22	TRI
HSF1	HSP90AB1	TRI
C1R	C1QA	PPI
YWHAG	TIAM1	PPI
CDC7	MCM3	PPI
F2	F2	PPI
DDEF1	REPS2	PPI
SETDB1	TOB1	PPI
PNMA1	UBQLN4	PPI
LBR	LBR	PPI
EPAS1	EIF3S6	PPI
IL18R1	IL1RAP	PPI
PRKDC	PCNA	PPI
PPARA	CPT2	TRI
CDC45L	MCM3	PPI
SETDB1	BARD1	PPI
KPNB1	RAN	PPI
SYNJ2	GRB2	PPI
PRKCD	DAB2	PPI
NAP1L1	TP53	PPI
DGKZ	DMD	PPI
PRKCA	RALBP1	PPI
RIPK2	CASP8	PPI
GPD2	ALDOA	PPI
TRIP13	C11orf54	PPI
PRKCA	HSPB8	PPI
ITCH	CPSF6	PPI
SKAP2	TGFBR1	PPI
GADD45G	PCNA	PPI
EDIL3	ITGAV	PPI
MCM7	CDC6	PPI
RAN	MBP	PPI
BUB3	BUB1	PPI
ACADM	ACADM	PPI
MCM7	MCM2	PPI
CPSF6	UBQLN4	PPI
MAP3K7	MAP3K7	PPI
WASF1	IL8	PPI
MED28	GRB2	PPI
TCERG1	NPM1	PPI
CASP8	VIM	PPI
EPDR1	UBQLN4	PPI
DYRK2	RAD54B	PPI
TUBB2C	TUBG1	PPI
GRB2	NPM1	PPI
HSF2	HSPA1B	TRI
PDLIM5	PRKCE	PPI
FOXM1	SLC2A2	TRI
C1S	SERPING1	PPI
FEZ1	HEATR2	PPI
THBS1	HRG	PPI
DYRK2	HIST2H2BE	PPI
FOXM1	U2AF2	TRI
PRIM1	TP53	PPI
PRKCA	SPP1	PPI
SPAG5	CDC2	PPI
MKI67	CBX5	PPI
PTN	APOBEC3G	PPI
PPAP2B	SHC1	PPI
PRMT6	HMGA1	PPI
KRT19	TUBG1	PPI
TP53	GNAI1	TRI
FADD	RALBP1	PPI
CPSF1	MCM2	PPI
AR	IL6ST	PPI
TIAM1	PRKCA	PPI
CLEC3B	HGF	PPI
KRT19	ABI2	PPI
PRKCD	PEBP1	PPI
YWHAZ	HSPA1B	PPI
TACC3	TTF2	PPI
RACGAP1	TUBA4A	PPI
CRYAA	CS	PPI
SORD	SORD	PPI
CDC2	VIM	PPI
HRAS	CDC25C	PPI
SYNCRIP	INSR	PPI
RXRA	GADD45A	PPI
TP53	KITLG	TRI
PPARBP	CRSP2	PPI
VIPR1	GNAI1	PPI
ANAPC7	CDH1	PPI
CDC7	MCM5	PPI
COIL	KALRN	PPI
SETDB1	HDAC2	PPI
PRKCA	ANXA2	PPI
YWHAB	CDC25C	PPI
NR0B2	ESR1	PPI
SPRY2	CBL	PPI
PRKCB1	GJA1	PPI
SHC1	LYN	PPI
YWHAG	RACGAP1	PPI
CCNE1	CDC2	PPI
BCL2L10	BAX	PPI
IGFBP5	F2	PPI
ATR	MSH2	PPI
PLAG1	KPNA2	PPI
KCNK1	UBE2I	PPI
NCOA3	AR	PPI
LCAT	APOA1	PPI
SULT1E1	BMPR2	PPI
SHCBP1	SHC1	PPI
YWHAG	GTPBP4	PPI
SKAP1	FYN	PPI
MAPK13	MBP	PPI
YWHAZ	CSF2RB	PPI
CDKN2A	GSPT1	PPI
CDC2	RAP1GAP	PPI
CEBPD	HPX	TRI
PRKCD	ADRB2	PPI
MAP3K5	TRAF5	PPI
ANXA3	TP53	PPI
HDAC6	TUBA4A	PPI
HMGA1	RXRA	PPI
TP53	MSI2	TRI
CDC2	NDE1	PPI
CDK5	PCTK1	PPI
CDC45L	POLA1	PPI
NFATC3	FOS	PPI
MCM7	MCM6	PPI
YWHAZ	HSPA1A	PPI
PTPN1	INSR	PPI
RXRA	APOA1	TRI
KPNA2	SLC2A2	PPI
TP53	SFN	TRI
TIAM1	PRKCE	PPI
SMURF2	RUNX3	PPI
FNTA	HRAS	PPI
PRKCD	LMNB1	PPI
TP53	CYP4F3	TRI
TUBA1B	PIK3R1	PPI
CSNK1D	DVL3	PPI
NCOA6	GHR	PPI
NCOA3	RXRA	PPI
DBF4	MCM3	PPI
PSMB9	NCOA3	PPI
TP53	PCNA	TRI
F2	SERPINC1	PPI
TOPBP1	EDD1	PPI
CFLAR	RIPK2	PPI
CDC6	CCNA2	PPI
TP53	CDC25C	PPI
RIPK2	CASP1	PPI
PRKCA	GJA1	PPI
SOS1	BIN1	PPI
HK2	UBQLN4	PPI
KHDRBS1	LYN	PPI
PSMD4	TCF3	PPI
LASP1	TRIP13	PPI
APOA1	APOB	PPI
CD36	LYN	PPI
MDC1	TP53	PPI
CFH	THBS1	PPI
CFL1	YWHAZ	PPI
PTCH1	CCNB1	PPI
APOA1	TTR	PPI
CDC2	NPM1	PPI
NCOA2	RXRA	PPI
DMD	UTRN	PPI
PER3	PER1	PPI
GADD45A	GADD45A	PPI
CDC6	PCNA	PPI
THRAP4	PPARA	PPI
HTRA2	BIRC3	PPI
RXRA	FUS	PPI
AGL	PRKAB1	PPI
YWHAZ	KIF5B	PPI
DMD	KRT19	PPI
FAS	PRKCA	PPI
PLAT	ANXA2	PPI
DVL3	DAB2	PPI
CBFA2T2	C8orf32	PPI
BCR	SFN	PPI
COIL	TGS1	PPI
ITGB8	TGFB1	PPI
FOS	MMP1	TRI
DBF4	MCM2	PPI
STAT1	IRF1	TRI
PPM1A	SMAD2	PPI
MINK1	YWHAZ	PPI
CHEK1	CDC25B	PPI
RRM2B	RRM2	PPI
SERPINA5	SERPINA5	PPI
F9	F8	PPI
CDC25B	SFN	PPI
SIX1	SIX1	PPI
PCNA	CDC2	PPI
PRKCA	HSPA1A	PPI
TRIP13	PBLD	PPI
TUBA1B	TUBG1	PPI
SOS1	PLCG1	PPI
AURKB	NDC80	PPI
SPHK1	LYN	PPI
NDRG1	MAOA	PPI
PRKCA	CD163	PPI
YWHAG	YWHAG	PPI
MAPK1	TNFRSF25	PPI
DDEF2	REPS2	PPI
RAN	AR	PPI
SMC2	NCAPD2	PPI
PPARA	PCK1	TRI
NDE1	TUBG1	PPI
RXRA	PPARA	PPI
RXRA	UBQLN4	PPI
MCM10	CEP70	PPI
RFC3	RFC4	PPI
EPRS	SYNCRIP	PPI
KLKB1	F12	PPI
CBX3	LBR	PPI
CDC25C	CCNA2	PPI
KIF15	MKI67	PPI
RGS2	PRKCA	PPI
SMARCA4	CCNE1	PPI
MATN2	COL4A2	PPI
ANXA2	APOH	PPI
MMP9	PLG	PPI
HMGA1	IRF1	PPI
SOX9	CD3E	TRI
GRIA3	LYN	PPI
BARD1	MSH2	PPI
AR	PIGR	TRI
RFX5	HDAC2	PPI
AURKA	CDC25B	PPI
SOX9	HSPA1A	PPI
KIF5B	SNAP25	PPI
ANPEP	TM4SF1	PPI
YWHAB	KIF23	PPI
COL4A5	DCN	PPI
HGS	STAM	PPI
MCM4	MCM2	PPI
MEP1A	MEP1A	PPI
PKM2	SHBG	PPI
SMAD2	LEF1	PPI
MELK	CDC25B	PPI
KSR1	YWHAZ	PPI
IRAK2	IRAK2	PPI
AVPR1A	PRKCA	PPI
MAPK9	NFATC3	PPI
ZHX2	NFYA	PPI
TP53	PRKAG2	TRI
RAN	SMAD2	PPI
TP53	HDAC2	PPI
CDC5L	MCM5	PPI
NDRG1	ILF3	PPI
SYNE1	LMNA	PPI
CDC25C	CCNB1	PPI
ANAPC7	BUB1B	PPI
PTN	GLYAT	PPI
MCM7	MCM10	PPI
GADD45B	PPARA	PPI
EIF4G3	PABPC1	PPI
HSPB1	CRYAA	PPI
PRKCD	ITGA6	PPI
PCNA	CCNB1	PPI
CBX5	SMARCA4	PPI
HGS	PAK1	PPI
AURKB	BIRC5	PPI
PRKCA	PLCB1	PPI
GPHN	TUBA4A	PPI
THBS1	F2	PPI
KIF23	RACGAP1	PPI
GADD45G	PPARA	PPI
AURKB	RACGAP1	PPI
NDRG1	KIF5B	PPI
UTP14A	PDCD5	PPI
RXRA	IGFBP3	PPI
PRKDC	TP53	PPI
DNMT3A	DNMT1	PPI
GADD45B	PCNA	PPI
TIAM1	PRKCD	PPI
NQO1	NQO1	PPI
COMT	TRIP13	PPI
ANPEP	ADH1A	TRI
FXYD1	ATP1A1	PPI
UBE2Z	TGFBR1	PPI
TP53	SMAD2	PPI
LCP2	GRB2	PPI
CDC2	AR	PPI
YWHAG	CKAP2	PPI
TTR	SETDB1	PPI
YWHAZ	TBXA2R	PPI
CDC7	CDK4	PPI
KIF4A	TTF2	PPI
PCNA	DNMT1	PPI
FOS	POLA1	TRI
TP53	RECK	TRI
HRAS	MAP2K1	PPI
CDC42EP5	CDC42	PPI
ORC6L	MCM2	PPI
BIN1	ITGA6	PPI
BIN1	BIN1	PPI
MCM4	MCM3	PPI
NFYA	NFYA	PPI
CDC45L	MCM7	PPI
YWHAZ	CDC25C	PPI
AR	JUN	PPI
IRAK2	HRAS	PPI
GPD1	PTN	PPI
BAG2	HSPA1A	PPI
PPARGC1A	NR1H4	PPI
CBX1	DNMT3A	PPI
KNG1	F2	PPI
UPP2	VIM	PPI
YWHAZ	CDC25B	PPI
TP53	OPTN	TRI
LYN	PRKCD	PPI
GRB2	CBL	PPI
KNG1	CTSS	PPI
RBP1	SAP30	PPI
SKAP2	LYN	PPI
TP53	PRKCE	TRI
PLK1	CCNB1	PPI
SELENBP1	TRIP13	PPI
CDC7	MCM4	PPI
PAIP2B	PABPC1	PPI
PKM2	PKM2	PPI
MCM10	CDKN2A	PPI
YWHAZ	SNF1LK	PPI
GNMT	PLEKHF2	PPI
IRF1	CCL5	TRI
GADD45G	RAN	PPI
DNMT3A	EED	PPI
TP53	PAFAH1B3	PPI
RIPK2	TRAF5	PPI
CDC6	CDKN2A	PPI
CCL5	GRB2	PPI
CEP55	AKAP9	PPI
SETDB1	ZFP64	PPI
RPS6KA3	ESR1	PPI
EDD1	KPNB1	PPI
PRKCA	GPM6A	PPI
ESR1	NR2F1	PPI
IRAK1	JUN	PPI
ANTXR2	COL4A2	PPI
F11	F2	PPI
JUN	MT2A	TRI
CPE	UTP14A	PPI
MAP3K7	FOS	PPI
BARD1	BARD1	PPI
TNPO1	RAN	PPI
UBE2I	AR	PPI
LCK	SHC1	PPI
ESR1	RXRA	PPI
BIRC3	GSPT1	PPI
STAT1	SP100	TRI
BIN1	FBP1	PPI
CDCA8	BIRC5	PPI
MIF	MIF	PPI
LEF1	ADA	TRI
BUB1B	AP2B1	PPI
KCNMA1	PTK2	PPI
STAT1	IRF1	PPI
ITGB3BP	RXRA	PPI
MATN2	COL1A1	PPI
KIT	PRKCB1	PPI
NFYA	JUN	PPI
THY1	ITGAV	PPI
CDC25C	LCK	PPI
F2	AMBP	PPI
ESR1	GNAI1	PPI
SGK3	ITCH	PPI
TCERG1	BARD1	PPI
FANCI	FANCD2	PPI
UTP14A	CEP70	PPI
SHC1	PRKCD	PPI
PRPF40A	U2AF2	PPI
HSPB1	HSPB8	PPI
HSPB8	BAG3	PPI
MMP12	PLAUR	PPI
MED12	MED12	PPI
RIT1	SMAD2	PPI
SIP1	U2AF2	PPI
PLK1	ECT2	PPI
FANCD2	NBN	PPI
PAFAH1B3	BRD7	PPI
ILF2	PRKDC	PPI
ANXA2	S100A10	PPI
TP53	HSPB1	PPI
ITGA6	GRB2	PPI
TRIM24	TRIM24	PPI
PRKCB1	LMNB1	PPI
YWHAG	MCM5	PPI
GNAO1	RGS1	PPI
GNA14	ADRB2	PPI
KCNMA1	KCNMA1	PPI
RAMP3	RAMP3	PPI
PLP2	PLP2	PPI
CDC45L	CDKN2A	PPI
TP53	GPC3	TRI
PON1	APOA1	PPI
GZMA	LMNB1	PPI
SNRPD2	SNRPD1	PPI
YWHAG	PRKCD	PPI
THRAP4	ESR1	PPI
PRKCA	LMNA	PPI
#GO	P value	Name	Type	Definition
GO:0005737	0.0005975255	cytoplasm	cellular_component	All of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
GO:0030194	0.000519256	positive regulation of blood coagulation	biological_process	Any process that activates or increases the frequency, rate or extent of blood coagulation.
GO:0005886	0.0001546018	plasma membrane	cellular_component	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
GO:0007076	0.006602999	mitotic chromosome condensation	biological_process	The cell cycle process whereby chromatin structure is compacted prior to and during mitosis in eukaryotic cells.
GO:0005829	2.461733e-10	cytosol	cellular_component	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
GO:0000775	0.005453326	chromosome, centromeric region	cellular_component	The region of a chromosome that includes the centromeric DNA and associated proteins. In monocentric chromosomes, this region corresponds to a single area of the chromosome, whereas in holocentric chromosomes, it is evenly distributed along the chromosome.
GO:0000077	0.009112262	DNA damage checkpoint	biological_process	A signal transduction pathway, induced by DNA damage, that blocks cell cycle progression (in G1, G2 or metaphase) or slows the rate at which S phase proceeds.
GO:0032139	0.006602999	dinucleotide insertion or deletion binding	molecular_function	Interacting selectively and non-covalently with double-stranded DNA containing a dinucleotide insertion or deletion.
GO:0005576	1.641665e-13	extracellular region	cellular_component	The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
GO:0005615	0.0003533156	extracellular space	cellular_component	That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.
GO:0006090	0.00456366	pyruvate metabolic process	biological_process	The chemical reactions and pathways involving pyruvate, 2-oxopropanoate.
GO:0005813	0.001459923	centrosome	cellular_component	A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle.
GO:0019899	0.0002044171	enzyme binding	molecular_function	Interacting selectively and non-covalently with any enzyme.
GO:0005654	1.012747e-26	nucleoplasm	cellular_component	That part of the nuclear content other than the chromosomes or the nucleolus.
GO:0006297	0.004814553	nucleotide-excision repair, DNA gap filling	biological_process	Repair of the gap in the DNA helix by DNA polymerase and DNA ligase after the portion of the strand containing the lesion has been removed by pyrimidine-dimer repair enzymes.
GO:0006260	1.267801e-29	DNA replication	biological_process	The cellular metabolic process whereby new strands of DNA are synthesized. The template for replication can either be an existing DNA molecule or RNA.
GO:0032133	2.503462e-05	chromosome passenger complex	cellular_component	A eukaryotically conserved protein complex that localizes to kinetochores in early mitosis, the spindle mid-zone in anaphase B and to the telophase midbody. It has been proposed that the passenger complex coordinates various events based on its location to different structures during the course of mitosis. Complex members include the BIR-domain-containing protein Survivin, Aurora B kinase, INCENP and Borealin.
GO:0008656	0.009112262	caspase activator activity	molecular_function	Increases the rate of proteolysis catalyzed by a caspase.
GO:0046966	0.009112262	thyroid hormone receptor binding	molecular_function	Interacting selectively and non-covalently with a thyroid hormone receptor.
GO:0030521	0.002718454	androgen receptor signaling pathway	biological_process	Any series of molecular signals generated as a consequence of an androgen binding to its receptor.
GO:0032405	0.001912136	MutLalpha complex binding	molecular_function	Interacting selectively and non-covalently with the mismatch repair complex MutLalpha.
GO:0005515	2.236458e-28	protein binding	molecular_function	Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
GO:0000796	0.004465855	condensin complex	cellular_component	A multisubunit protein complex that plays a central role in chromosome condensation.
GO:0005634	9.289168e-08	nucleus	cellular_component	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.