FLUXestimator

M171: This is the central metabolic map of human. This metabolic network covers the metabolism, transport, and biosynthesis of carbohydrate, amino acids, fatty acids and lipids, glycan, and nucleic acids in human, including 663 genes of 395 enzymes, 1381 reactions, 1468 metabolites, and 116 transporter genes of 35 metabolites in human collected from KEGG and other literatures. After the network simplification, we have simplified and reconstructed this network into 171 modules belong to 22 super module classes and 70 metabolites, out of which 66 are intermediate substrates. We recommend this network for a general characterization of metabolic landscapes.

The 22 super module classes cover glycolysis and TCA cycle, serine and related amino acids metabolism, pentose phosphate, fatty acids biosynthesis/metabolism, aspartate and related amino acids metabolism, beta-alanie metabolism, propanoyl-CoA metabolism, glutamate, glutamine and related amino acids metabolism, leucine and valine and isoleucine (branched chain amin acids) metabolism, urea cycle, spermine metabolism, transporters, hyaluronic acid synthesis, glycogen synthesis, N-linked glycan synthesis, O-linked glycan synthesis, sialic acid synthesis, chondroitin sulfate, dermatan sulfate, heparan sulfate and other glycosaminoglycan biosynthesis, purine synthesis, pyrimidine synthesis, and steroid hormone synthesis.

The figure below illustrates the reconstructed network and super modules. Complete information of the reconstructed network is available in the downloads.

M171

M171_NAD: This network is the M171 network plus a consideration of redox balance by including the balance of the production and consumption of NAD+. In M171, we identified 23 modules including glycolysis, fatty acids oxidation, amino acids metabolism, production of Acetyl-CoA and Succinyl-CoA, and nucleic acid metabolism that consume NAD+, and 6 modules including lactate production and fatty acid biosynthesis that produce NAD+. We also include a module of the de novo biosynthesis and salvage pathway that produce NAD+. NAD+ serves as an additional intermediate metabolite that introduces a constraint of the balance between the total flux of the 23 NAD+ consuming reactions and the 7 NAD+ generating reactions. The other part of this network is the same as M171. See details of the M171 network by selecting the input network as M171. downloads.

M171_NAD

KEGG: KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of human is formed by 100 modules, including 10 sub-networks, 1333 metabolic genes and 570 intermediate metabolites. We recommend this network for a general characterization of global metabolic variations. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

KEGG

GGSL: We collected the central metabolism network and its branches of glucose and glutamine metabolism in subcellular localization resolution from KEGG database. We further manually curated the reaction information from literature data, based on our previously curated metabolic network. This subnetwork is named Glucose-Glutamine Subcellular Localization (GGSL) network. As subcellular compartments have different levels of enzymes, substrates, biochemical characteristics, and kinetic parameters, sub-cellular localization information of reactions is needed to accurately assess their stoichiometric relations. The reconstructed GGSL network includes six major pathways, namely glycolysis, upper and lower parts of TCA cycle, glutaminolysis, glutamine and glutamate metabolism, and glutathione metabolism, and six minor branches, namely Glyceraldehyde 3-phosphate (G3P) to nucleotide synthesis, 3-Phospho-D-glycerate (3PD) to serine synthesis, aspartate-malate shuttle, mitochondrial citrate fueling of fatty acid synthesis, transport of 2-Oxoglutarate (2OG) to cytosol, and transform of 2OG to 2-Hydroxyglutarate (2HG). The human GGSL network covers 41 reaction modules, 37 intermediate metabolites, 241 enzymes, and 254 genes in cytosol, mitochondria, and extracellular regions.

We recommend this network for characterization of the central metabolic variations in cancer and inflammatory diseases or conditions with varied redox balance. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

GGSL

Glucose-TCAcycle: This metabolic network is formed by glycolysis, pentose phosphate and TCA cycle pathways in human, which covers essential metabolites in fueling energy production and cell growth. This model focuses on a closed system of metabolism that assumes the major source of glucose are for feeding the energy production and biosynthesis. The network includes 65 genes of 45 enzymes. We reconstructed this network into 15 modules and 12 intermediate metabolites.

We recommend this network for characterization of glycolysis and TCA cycle only. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Glucose-TCAcycle

Glucose-Glutaminolysis: This metabolic network is formed by glycolysis, pentose phosphate, TCA cycle, and glutaminolysis pathways in human, which covers essential metabolites in fueling energy production and cell growth. This model focuses on a closed system of glucose and glutamine metabolism that assumes the major source of glucose and glutamine are for feeding the energy production. The network includes 132 genes of 61 enzymes, 175 reactions and 194 metabolites. We reconstructed this network into 23 modules, 17 intermediate metabolites and 4 pseudo-end metabolites.

We recommend this network for characterization of glycolysis, TCA cycle, glutaminolysis and their impacts when users assume the major flow of glutamine is utilized to fuel the TCA cycle, such as in certain cancer systems. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Glucose-Glutaminolysis

Glucose-Glutamine: This metabolic network is formed by glycolysis, pentose phosphate, TCA cycle, and glutaminolysis pathways in human, which covers essential metabolites in fueling energy production and cell growth. This model focuses on a closed system of glucose and glutamine metabolism that assumes the major source of glucose and glutamine are for feeding the energy production. The network includes 176 genes of 101 enzymes, 247 reactions and 288 metabolites. We reconstructed this network into 27 modules, 17 intermediate metabolites and 8 pseudo-end metabolites (which include the exchange between glutamine and glutamate, and synthesis/transform of glutamine and glutamate from other amino acids).

We recommend this network for a general characterization of the central metabolic pathway, evaluating flux distribution of different carbon sources, and studying glutamate and GABA biosynthesis in the neuron system. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Glucose-Glutamine

BCAA: This is the metabolic network of Branched Chain Amino Acids (BCAA) metabolism in human. We have collected related reactions including leucine, valine and isoleucine metabolism and biosynthesis of branched chain fatty acids. The network includes 60 genes of 52 enzymes, 207 reactions and 261 metabolites. We reconstructed this network into 15 modules, 6 intermediate metabolites and 1 pseudo-end metabolites.

We recommend this network for the specific analysis of BCAA metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

BCAA

Acetylcholine: This is the metabolic network of biosynthesis and metabolism of the neurotransmitter acetylcholine in human. We have collected related reactions from glycerol 3-phosphate to acetylcholine and its metabolism into choline. The network includes 80 genes of 29 enzymes, 76 reactions and 103 metabolites. We reconstructed this network into 15 modules, 6 intermediate metabolites and 2 pseudo-end metabolites.

We recommend this network for the specific analysis of acetylcholine metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Acetylcholine

Dopamine: This is the metabolic network of biosynthesis and metabolism of the neurotransmitter dopamine in human. We have collected related reactions from tyrosine to dopamine and its metabolism/biosynthesis into downstream products such as noradrenaline and adrenaline. The network includes 23 genes of 15 enzymes, 107 reactions and 152 metabolites. We reconstructed this network into 9 modules, 4 intermediate metabolites and 5 pseudo-end metabolites.

We recommend this network for the specific analysis of dopamine metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Dopamine

Histamine: This is the metabolic network of biosynthesis and metabolism of the neurotransmitter histamine in human, which also serves as an organic nitrogenous compound involved in local immune responses. We have collected related reactions from histidine to carnosine and histamine. The network includes 23 genes of 17 enzymes, 85 reactions and 129 metabolites. We reconstructed this network into 6 modules, 3 intermediate metabolites and 2 pseudo-end metabolites.

We recommend this network for the specific analysis of histamine metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Histamine

Serotonin: This is the metabolic network of biosynthesis and metabolism of the neurotransmitter serotonin in human. We have collected related reactions from tryptophan to oxitriptan and serotonin, and its downstream metabolism into melatonin and degradation. The network includes 24 genes of 17 enzymes, 155 reactions and 241 metabolites. We reconstructed this network into 8 modules, 4 intermediate metabolites and 5 pseudo-end metabolites.

We recommend this network for the specific analysis of serotonin metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Serotonin

IronIon: This is the sub-cellular specific metabolic network of iron ion in human. We have collected the reactions including iron ion transportation, ferric ion reduction, and utilization of iron ion in heme and ion sulfur biosynthesis and Fenton reaction. The network includes 141 genes of 24 enzymes, 47 reactions and 105 metabolites. We reconstructed this network into 15 modules, 8 intermediate metabolites and 4 pseudo-end metabolites.

We recommend this network for the specific analysis of iron ion metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

IronIon

MGF: The Methionine Glutathione Folic Acid (MGF) network specifically focuses on methionine, DNA methylation and related metabolism. It includes seven major modules that cover the metabolism of methionine, glutathione, and folic acids. The human MGF network includes 98 genes of 72 enzymes. We reconstructed this network into 8 modules and 5 intermediate metabolites.

We recommend this network for characterizing the metabolic flux distribution of methionine metabolism, DNA methylation, glutathione biosynthesis and metabolism, and folic acid metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

MGF

Lipid metabolism: The lipids metabolism network was manually curated by including the biosynthesis and metabolism of Fatty Acyls, Phospholipids, Lysophospholipids, Glycerolipids, Sphingolipids, Prenol lipids, Sterol lipids, Steroid Hormone Biosynthesis, Primary Bile Acids, and Steroid, etc. The human Lipids metabolism network includes 320 genes of 165 enzymes. We reconstructed this network into 112 modules and 93 intermediate metabolites.

We recommend this network for characterizing the metabolism and biosynthesis of lipids. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Lipid metabolism

MHC-I: MHC Class I Antigen Presentation (MHC-I) network can be viewed as a metabolic process. To the best of our knowledge, there is no established systems biology model of this process in the public domain. We first manually collected and curated the biological processes that are involved in the MHC class I antigen presentation pathway via an extensive literature review by multiple immunologists studying antigen presentation, exocytosis, endocytosis. The first step of MHC class I antigen presentation is ubiquitination and proteolysis, which involves E1/E2/E3 and proteosome complexes. We also consider the approach of de-ubiquitination, which serves as an out branch of ubiquitination that decreases the number of ubiquitinated proteins. We consider the generation of MHC class I complex include three major steps in ER, namely (1) transporting of peptide into ER, (2) trimming of peptides in ER, and (3) peptide loading complex that generate MHC class I complex with loaded antigens. The MHC class I complex is further transported from ER to Golgi and from Golgi to cell membrane, which involve the genes in exocytosis process. Regulatory genes of vesicular transport, antigen quality checking genes, and the flow from trans-Golgi network to late endosome serve as out branch in these approaches. Noted, we also consider the recycling of the MHC class I complex expressed on cell surface, which involves the endocytosis and retrograde transport processes. We further collected the genes involved in these biological processes via multiple pathway resources including KEGG, Reactome, and Gene Ontology.

The human MHC-I metabolism network includes 325 genes of 9 major reaction steps. We reconstructed this network into 9 modules and 8 intermediate metabolites.

We recommend this network for characterizing the activity level of MHC class I antigen presentation only for the MHC class I presenting cells or tissues. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

MHC-I

M171: This is the central metabolic map of human. This metabolic network covers the metabolism, transport, and biosynthesis of carbohydrate, amino acids, fatty acids and lipids, glycan, and nucleic acids in mouse, including 719 genes of 395 enzymes, 1381 reactions, 1468 metabolites, and 116 transporter genes of 35 metabolites in human collected from KEGG and other literatures. After the network simplification, we have simplified and reconstructed this network into 171 modules belong to 22 super module classes and 70 metabolites, out of which 66 are intermediate substrates. We recommend this network for a general characterization of metabolic landscapes.

The 22 super module classes cover glycolysis and TCA cycle, serine and related amino acids metabolism, pentose phosphate, fatty acids biosynthesis/metabolism, aspartate and related amino acids metabolism, beta-alanie metabolism, propanoyl-CoA metabolism, glutamate, glutamine and related amino acids metabolism, leucine and valine and isoleucine (branched chain amin acids) metabolism, urea cycle, spermine metabolism, transporters, hyaluronic acid synthesis, glycogen synthesis, N-linked glycan synthesis, O-linked glycan synthesis, sialic acid synthesis, chondroitin sulfate, dermatan sulfate, heparan sulfate and other glycosaminoglycan biosynthesis, purine synthesis, pyrimidine synthesis, and steroid hormone synthesis.

The figure below illustrates the reconstructed network and super modules. Complete information of the reconstructed network is available in the downloads.

M171

M171_NAD: This network is the M171 network plus a consideration of redox balance by including the balance of the production and consumption of NAD+. In M171, we identified 23 modules including glycolysis, fatty acids oxidation, amino acids metabolism, production of Acetyl-CoA and Succinyl-CoA, and nucleic acid metabolism that consume NAD+, and 6 modules including lactate production and fatty acid biosynthesis that produce NAD+. We also include a module of the de novo biosynthesis and salvage pathway that produce NAD+. NAD+ serves as an additional intermediate metabolite that introduces a constraint of the balance between the total flux of the 23 NAD+ consuming reactions and the 7 NAD+ generating reactions. The other part of this network is the same as M171. See details of the M171 network by selecting the input network as M171. downloads.

M171_NAD

KEGG: KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of mouse is formed by 100 modules, including 10 sub-networks, 569 metabolic genes and 134 intermediate metabolites. We recommend this network for a general characterization of global metabolic variations. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

KEGG

GGSL: We collected the central metabolism network and its branches of glucose and glutamine metabolism in subcellular localization resolution from KEGG database. We further manually curated the reaction information from literature data, based on our previously curated metabolic network. This subnetwork is named Glucose-Glutamine Subcellular Localization (GGSL) network. As subcellular compartments have different levels of enzymes, substrates, biochemical characteristics, and kinetic parameters, sub-cellular localization information of reactions is needed to accurately assess their stoichiometric relations. The reconstructed GGSL network includes six major pathways, namely glycolysis, upper and lower parts of TCA cycle, glutaminolysis, glutamine and glutamate metabolism, and glutathione metabolism, and six minor branches, namely Glyceraldehyde 3-phosphate (G3P) to nucleotide synthesis, 3-Phospho-D-glycerate (3PD) to serine synthesis, aspartate-malate shuttle, mitochondrial citrate fueling of fatty acid synthesis, transport of 2-Oxoglutarate (2OG) to cytosol, and transform of 2OG to 2-Hydroxyglutarate (2HG). The mouse GGSL network covers 41 reaction modules, 37 intermediate metabolites, 241 enzymes, and 237 genes in cytosol, mitochondria, and extracellular regions.

We recommend this network for characterization of the central metabolic variations in cancer and inflammatory diseases or conditions with varied redox balance. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

GGSL

Glucose-TCAcycle: This metabolic network is formed by glycolysis, pentose phosphate and TCA cycle pathways in mouse, which covers essential metabolites in fueling energy production and cell growth. This model focuses on a closed system of metabolism that assumes the major source of glucose are for feeding the energy production and biosynthesis. The network includes 66 genes of 45 enzymes. We reconstructed this network into 15 modules and 12 intermediate metabolites.

We recommend this network for characterization of glycolysis and TCA cycle only. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Glucose-TCAcycle

Glucose-Glutaminolysis: This metabolic network is formed by glycolysis, pentose phosphate, TCA cycle, and glutaminolysis pathways in mouse, which covers essential metabolites in fueling energy production and cell growth. This model focuses on a closed system of glucose and glutamine metabolism that assumes the major source of glucose and glutamine are for feeding the energy production. The network includes 134 genes of 61 enzymes, 175 reactions and 194 metabolites. We reconstructed this network into 23 modules, 17 intermediate metabolites and 4 pseudo-end metabolites.

We recommend this network for characterization of glycolysis, TCA cycle, glutaminolysis and their impacts when users assume the major flow of glutamine is utilized to fuel the TCA cycle, such as in certain cancer systems. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Glucose-Glutaminolysis

Glucose-Glutamine: This metabolic network is formed by glycolysis, pentose phosphate, TCA cycle, and glutaminolysis pathways in mouse, which covers essential metabolites in fueling energy production and cell growth. This model focuses on a closed system of glucose and glutamine metabolism that assumes the major source of glucose and glutamine are for feeding the energy production. The network includes 165 genes of 101 enzymes, 247 reactions and 288 metabolites. We reconstructed this network into 27 modules, 17 intermediate metabolites and 8 pseudo-end metabolites (which include the exchange between glutamine and glutamate, and synthesis/transform of glutamine and glutamate from other amino acids).

We recommend this network for a general characterization of the central metabolic pathway, evaluating flux distribution of different carbon sources, and studying glutamate and GABA biosynthesis in the neuron system. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Glucose-Glutamine

BCAA: This is the metabolic network of Branched Chain Amino Acids (BCAA) metabolism in mouse. We have collected related reactions including leucine, valine and isoleucine metabolism and biosynthesis of branched chain fatty acids. The network includes 64 genes of 52 enzymes, 207 reactions and 261 metabolites. We reconstructed this network into 15 modules, 6 intermediate metabolites and 1 pseudo-end metabolites.

We recommend this network for the specific analysis of BCAA metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

BCAA

Acetylcholine: This is the metabolic network of biosynthesis and metabolism of the neurotransmitter acetylcholine in mouse. We have collected related reactions from glycerol 3-phosphate to acetylcholine and its metabolism into choline. The network includes 86 genes of 29 enzymes, 76 reactions and 103 metabolites. We reconstructed this network into 15 modules, 6 intermediate metabolites and 2 pseudo-end metabolites.

We recommend this network for the specific analysis of acetylcholine metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Acetylcholine

Dopamine: This is the metabolic network of biosynthesis and metabolism of the neurotransmitter dopamine in mouse. We have collected related reactions from tyrosine to dopamine and its metabolism/biosynthesis into downstream products such as noradrenaline and adrenaline. The network includes 24 genes of 15 enzymes, 107 reactions and 152 metabolites. We reconstructed this network into 9 modules, 4 intermediate metabolites and 5 pseudo-end metabolites.

We recommend this network for the specific analysis of dopamine metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Dopamine

Histamine: This is the metabolic network of biosynthesis and metabolism of the neurotransmitter histamine in mouse, which also serves as an organic nitrogenous compound involved in local immune responses. We have collected related reactions from histidine to carnosine and histamine. The network includes 24 genes of 17 enzymes, 85 reactions and 129 metabolites. We reconstructed this network into 6 modules, 3 intermediate metabolites and 2 pseudo-end metabolites.

We recommend this network for the specific analysis of histamine metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Histamine

Serotonin: This is the metabolic network of biosynthesis and metabolism of the neurotransmitter serotonin in mouse. We have collected related reactions from tryptophan to oxitriptan and serotonin, and its downstream metabolism into melatonin and degradation. The network includes 26 genes of 17 enzymes, 155 reactions and 241 metabolites. We reconstructed this network into 8 modules, 4 intermediate metabolites and 5 pseudo-end metabolites.

We recommend this network for the specific analysis of serotonin metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Serotonin

IronIon: This is the sub-cellular specific metabolic network of iron ion in mouse. We have collected the reactions including iron ion transportation, ferric ion reduction, and utilization of iron ion in heme and ion sulfur biosynthesis and Fenton reaction. The network includes 152 genes of 24 enzymes, 47 reactions and 105 metabolites. We reconstructed this network into 15 modules, 8 intermediate metabolites and 4 pseudo-end metabolites.

We recommend this network for the specific analysis of iron ion metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

IronIon

MGF: The Methionine Glutathione Folic Acid (MGF) network specifically focuses on methionine, DNA methylation and related metabolism. It includes seven major modules that cover the metabolism of methionine, glutathione, and folic acids. The mouse MGF network includes 91 genes of 72 enzymes. We reconstructed this network into 8 modules and 5 intermediate metabolites.

We recommend this network for characterizing the metabolic flux distribution of methionine metabolism, DNA methylation, glutathione biosynthesis and metabolism, and folic acid metabolism. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

MGF

Lipid metabolism: The lipids metabolism network was manually curated by including the biosynthesis and metabolism of Fatty Acyls, Phospholipids, Lysophospholipids, Glycerolipids, Sphingolipids, Prenol lipids, Sterol lipids, Steroid Hormone Biosynthesis, Primary Bile Acids, and Steroid, etc. The mouse Lipids metabolism network includes 334 genes of 165 enzymes. We reconstructed this network into 112 modules and 93 intermediate metabolites.

We recommend this network for characterizing the metabolism and biosynthesis of lipids. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Lipid metabolism

MHC-I: MHC Class I Antigen Presentation (MHC-I) network can be viewed as a metabolic process. To the best of our knowledge, there is no established systems biology model of this process in the public domain. We first manually collected and curated the biological processes that are involved in the MHC class I antigen presentation pathway via an extensive literature review by multiple immunologists studying antigen presentation, exocytosis, endocytosis. The first step of MHC class I antigen presentation is ubiquitination and proteolysis, which involves E1/E2/E3 and proteosome complexes. We also consider the approach of de-ubiquitination, which serves as an out branch of ubiquitination that decreases the number of ubiquitinated proteins. We consider the generation of MHC class I complex include three major steps in ER, namely (1) transporting of peptide into ER, (2) trimming of peptides in ER, and (3) peptide loading complex that generate MHC class I complex with loaded antigens. The MHC class I complex is further transported from ER to Golgi and from Golgi to cell membrane, which involve the genes in exocytosis process. Regulatory genes of vesicular transport, antigen quality checking genes, and the flow from trans-Golgi network to late endosome serve as out branch in these approaches. Noted, we also consider the recycling of the MHC class I complex expressed on cell surface, which involves the endocytosis and retrograde transport processes. We further collected the genes involved in these biological processes via multiple pathway resources including KEGG, Reactome, and Gene Ontology.

The mouse MHC-I metabolism network includes 302 genes of 9 major reaction steps. We reconstructed this network into 9 modules and 8 intermediate metabolites.

We recommend this network for characterizing the activity level of MHC class I antigen presentation only for the MHC class I presenting cells or tissues. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

MHC-I

Ciona robusta: Ciona robusta (yellow sea squirt) is a species of marine invertebrate in the genus Ciona of the family Cionidae. The holotype was collected on the northeastern coast of Honshu Island, Japan. Populations of Ciona intestinalis known as Ciona intestinalis type A found in the Mediterranean Sea, the Pacific Ocean, east coast of North America, and the Atlantic coasts of South Africa have been shown to be Ciona robusta, KEGG code: cin.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Ciona robusta is formed by 59 modules, including 6 sub-networks, 222 metabolic genes and 82 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Ciona robusta

Zea mays: Zea mays (corn), also called Indian corn or maize, cereal plant of the grass family (Poaceae) and its edible grain. The domesticated crop originated in the Americas and is one of the most widely distributed of the world’s food crops. Corn is used as livestock feed, as human food, as biofuel, and as raw material in industry, KEGG code: zma.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Zea mays is formed by 86 modules, including 4 sub-networks, 1093 metabolic genes and 104 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Zea mays

Danio rerio: Danio rerio (zebrafish) is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often called a tropical fish although both tropical and subtropical). It is also found in private ponds.

The zebrafish is an important and widely used vertebrate model organism in scientific research, for example in drug development, in particular pre-clinical development. It is also notable for its regenerative abilities, and has been modified by researchers to produce many transgenic strains, KEGG code: dme.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Danio rerio is formed by 95 modules, including 10 sub-networks, 577 metabolic genes and 126 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Danio rerio

Gallus gallus: Gallus gallus (The red junglefowl) is a tropical bird in the family Phasianidae. It ranges across much of Southeast Asia and parts of South Asia. It was formerly known as the Bankiva or Bankiva Fowl. It is the species that gave rise to the chicken (Gallus gallus domesticus); the grey junglefowl, Sri Lankan junglefowl and green junglefowl have also contributed genetic material to the gene pool of the chicken.

Evidence from the molecular level derived from whole-genome sequencing revealed that the chicken was domesticated from red junglefowl about 8,000 years ago, with this domestication event involving multiple maternal origins. Since then, their domestic form has spread around the world where they are kept by humans for their meat, eggs, and companionship, KEGG code: gga.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Gallus gallus is formed by 82 modules, including 6 sub-networks, 402 metabolic genes and 112 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Gallus gallus

Xenopus tropicalis: Xenopus tropicalis (The western clawed frog) is a species of frog in the family Pipidae, also known as tropical clawed frog. It is the only species in the genus Xenopus to have a diploid genome. Its genome has been sequenced, making it a significant model organism for genetics that complements the related species Xenopus laevis (the African clawed frog), a widely used vertebrate model for developmental biology. X. tropicalis also has a number of advantages over X. laevis in research, such as a much shorter generation time (<5 months), smaller size (4–6 cm (1.6–2.4 in) body length), and a larger number of eggs per spawn.

It is found in Benin, Burkina Faso, Cameroon, Ivory Coast, Equatorial Guinea, Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Nigeria, Senegal, Sierra Leone, Togo, and possibly Mali. Its natural habitats are subtropical or tropical moist lowland forests, moist savanna, rivers, intermittent rivers, swamps, freshwater lakes, intermittent freshwater lakes, freshwater marshes, intermittent freshwater marshes, rural gardens, heavily degraded former forests, water storage areas, ponds, aquaculture ponds, and canals and ditches, KEGG code: xtr.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Xenopus tropicalis is formed by 94 modules, including 10 sub-networks, 502 metabolic genes and 126 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Xenopus tropicalis

Rattus norvegicus: Rattus norvegicus (The brown rat), also known as the common rat, street rat, sewer rat, wharf rat, Hanover rat, Norway rat and Norwegian rat, is a widespread species of common rat. One of the largest muroids, it is a brown or grey rodent with a head and body length of up to 28 cm (11 in) long, and a tail slightly shorter than that. It weighs between 140 and 500 g (4.9 and 17.6 oz). Thought to have originated in northern China and neighbouring areas, this rodent has now spread to all continents except Antarctica, and is the dominant rat in Europe and much of North America. With rare exceptions, the brown rat lives wherever humans live, particularly in urban areas.

Selective breeding of the brown rat has produced the fancy rat (rats kept as pets), as well as the laboratory rat (rats used as model organisms in biological research). Both fancy rats and laboratory rats are of the domesticated subspecies Rattus norvegicus domestica. Studies of wild rats in New York City have shown that populations living in different neighborhoods can evolve distinct genomic profiles over time, by slowly accruing different traits, KEGG code: rno.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Rattus norvegicus is formed by 99 modules, including 10 sub-networks, 581 metabolic genes and 132 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Rattus norvegicus

Escherichia coli K-12: Escherichia coli K-12 A strain was isolated from a stool sample of a patient convalescent from diphtheria and was labelled K-12 (not an antigen) in 1922 at Stanford University. This isolate was used in 1940s by Charles E. Clifton to study nitrogen metabolism, who deposited it in ATCC (strain ATCC 10798 Archived 2011-07-25 at the Wayback Machine) and lent it to Edward Tatum for his tryptophan biosynthesis experiments, despite its idiosyncrasies due to the F+ λ+ phenotype. In the course of the passages it lost its O antigen and in 1953 was cured first of its lambda phage (strain W1485 Archived 2011-07-25 at the Wayback Machine by UV by Joshua Lederberg and colleagues) and then in 1985 of the F plasmid by acridine orange curing.[citation needed] Strains derived from MG1655 include DH1, parent of DH5α and in turn of DH10B (rebranded as TOP10 by Invitrogen). An alternative lineage from W1485 is that of W2637 (which contains an inversion rrnD-rrnE), which in turn resulted in W3110. Due to the lack of specific record-keeping, the pedigree of strains was not available and had to be inferred by consulting lab-book and records in order to set up the E. coli Genetic Stock Centre at Yale by Barbara Bachmann. The different strains have been derived through treating E. coli K-12 with agents such as nitrogen mustard, ultra-violet radiation, X-ray etc. An extensive list of Escherichia coli K-12 strain derivatives and their individual construction, genotypes, phenotypes, plasmids and phage information can be viewed at Ecoliwiki, KEGG code: eco.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Escherichia coli K-12 is formed by 84 modules, including 7 sub-networks, 378 metabolic genes and 102 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Escherichia coli K-12

Bacillus subtilis 168: Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus Bacillus, B. subtilis is rod-shaped, and can form a tough, protective endospore, allowing it to tolerate extreme environmental conditions. B. subtilis has historically been classified as an obligate aerobe, though evidence exists that it is a facultative anaerobe. B. subtilis is considered the best studied Gram-positive bacterium and a model organism to study bacterial chromosome replication and cell differentiation. It is one of the bacterial champions in secreted enzyme production and used on an industrial scale by biotechnology companies. the strain designated '168' is the most widely used. Strain 168 is a tryptophan auxotroph isolated after X-ray mutagenesis of B. subtilis Marburg strain and is widely used in research due to its high transformation efficiency, KEGG code: bsu.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Bacillus subtilis 168 is formed by 63 modules, including 4 sub-networks, 258 metabolic genes and 85 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Bacillus subtilis 168

Pseudomonas fluorescens SBW25: Pseudomonads are ubiquitous organisms distributed widely in the environment, including the soil and water and in association with various living host organisms. There are representatives such as Pseudomonas aeruginosa that represent one of the most prevalent causes of opportunistic infections in humans and is the most common cause of eventually fatal, persistent respiratory infections in cystic fibrosis (CF) patients. Others such as Pseudomonas fluorescens represent a physiologically diverse species that contributes greatly to the turnover of organic matter and, while present in soil, is abundant on the surfaces of plant roots and leaves. Of the plant-colonizing strains, some isolates are known to positively affect plant health and nutrition. The mechanistic bases of these effects remain unclear, but are known to include the production of plant-growth hormones, the suppression of pathogens (especially fungi and oomycetes) detrimental to plant health via competitive and / or allelopathic effects, and the direct elicitation of plant defence responses. To date the genome sequence of the Liverpool Epidemic Strain (LES) of P. aeruginosa and Pseudomonas fluorescens strain SBW25 has been determined, KEGG code: pfs.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Pseudomonas fluorescens SBW25 is formed by 66 modules, including 7 sub-networks, 345 metabolic genes and 88 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Pseudomonas fluorescens SBW25

Arabidopsis thaliana: Arabidopsis thaliana, the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant from the mustard family (Brassicaceae), native to Eurasia and Africa. Commonly found along the shoulders of roads and in disturbed land, it is generally considered a weed.

A winter annual with a relatively short lifecycle, A. thaliana is a popular model organism in plant biology and genetics. For a complex multicellular eukaryote, A. thaliana has a relatively small genome of around 135 megabase pairs. It was the first plant to have its genome sequenced, and is an important tool for understanding the molecular biology of many plant traits, including flower development and light sensing, KEGG code: ath.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Arabidopsis thaliana is formed by 86 modules, including 9 sub-networks, 581 metabolic genes and 105 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Arabidopsis thaliana

Azotobacter vinelandii DJ: Azotobacter vinelandii DJ is a strain of Azotobacter vinelandii. It is a gram-negative soil bacterium capable of converting atmospheric nitrogen gas (N2) into soluble ammonia (NH3) as well as into other important nitrogenous compounds. It is a model organism for the study of biological nitrogen fixation (BNF) (Tec-Campos, et al. Metabolic Engineering Communications 2020, KEGG code: avn.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Azotobacter vinelandii DJ is formed by 65 modules, including 8 sub-networks, 347 metabolic genes and 86 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Azotobacter vinelandii DJ

Synechocystis PCC 6803: Synechocystis sp. PCC6803 is a strain of unicellular, freshwater cyanobacteria. Synechocystis sp. PCC6803 is capable of both phototrophic growth by oxygenic photosynthesis during light periods and heterotrophic growth by glycolysis and oxidative phosphorylation during dark periods. Gene expression is regulated by a circadian clock and the organism can effectively anticipate transitions between the light and dark phases, KEGG code: syn.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Synechocystis PCC 6803 is formed by 51 modules, including 4 sub-networks, 199 metabolic genes and 64 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Synechocystis PCC 6803

Methanococcus voltae A3: Methanococcus voltae is a single-celled, gram-negative, coccoid-shaped organism that is a member of the domain Archaea . It belongs to a specific group called methanogens, or methane producers. Archaea thrive under extreme environmental conditions. Methanogenic archaeobacterium occur in anaerobic environments, such as the intestinal tracts of animals, freshwater and marine sediments, and sewage. They are capable of producing methane from a limited number of substrates, including carbon dioxide and hydrogen, acetate, and methylamines: an important source of natural gas. M. voltae’s main pathway for energy production is through methanogenesis. Overall, Methanococcus voltae A3 is a strain of Methanococcus voltae. It is a single-celled, gram-negative, coccoid-shaped organism that is a member of the domain Archaea, KEGG code: mvo.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Methanococcus voltae A3 is formed by 22 modules, including 3 sub-networks, 137 metabolic genes and 38 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Methanococcus voltae A3

Streptomyces coelicolor A3(2): Streptomyces coelicolor A3 (2) is an extensively studied model organism for the genetic studies of Streptomycetes - a genus known for the production of a vast number of bioactive compounds and complex regulatory networks controlling morphological differentiation and secondary metabolites production.(Pawlik et, al. J Mol Microbiol Biotechnol (DOI: 10.1159/000321501), KEGG code: sco.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Streptomyces coelicolor A3(2) is formed by 64 modules, including 7 sub-networks, 380 metabolic genes and 82 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Streptomyces coelicolor A3(2)

Methanosarcina acetivorans C2A: Methanosarcina acetivorans C2A is a strain of Methanosarcina acetivorans, a versatile methane-producing microbe found in diverse environments such as oil wells, trash dumps, deep-sea hydrothermal vents, and oxygen-depleted sediments beneath kelp beds. It is a marine methanogenic archaeon notable for its substrate utilization, genetic tractability, and novel energy conservation mechanisms, KEGG code: mac.

KEGG directly offers 245 metabolic modules. A module in KEGG is a functional unit of reactions in metabolic pathways that form a chain or chain-like shape. Each module has one or a few inputs or outputs and its intermediate steps do not contain significant in-/out-branches. Thus, the KEGG modules naturally form a genome scale metabolic network. Compared to the M171 network, the KEGG module network omits more branches and contains multiple disconnected subnetworks. When building species specific networks, we first took the modules that are present in the species, identified the subnetworks formed by the modules and removed single modules. Single modules are excluded from FLUXestimator analysis.

The KEGG-module formed genome-wide metabolic map of Methanosarcina acetivorans C2A is formed by 42 modules, including 2 sub-networks, 216 metabolic genes and 51 intermediate metabolites. The figure below illustrates the reconstructed network. Complete information of the reconstructed network is available in the downloads.

Methanosarcina acetivorans C2A