The Large-Scale Organization of Metabolic Networks

The Large-Scale Organization of Metabolic Networks H. Jeong B. Tombor R. Albert Z. N. Oltvai A.-L. Barabási

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The Large-Scale Organization of Metabolic Networks 2000 Nature / arXiv 10.1038/35036627 cond-mat/0010278 jeong2000-metabolic-networks jeong2000-metabolic-networks.txt, the project's staged copy 609aed732da4d48825669b095adb0b6a5c96d522 arxiv-open biology

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them The core metabolic networks of 43 organisms across archaea, bacteria and eukaryota, as drawn from the WIT pathway-genome database. Quotation withheld because this record is not cleared for redistribution. Is the topology of a metabolic network the homogeneous random kind predicted by Erdos-Renyi, or the heterogeneous scale-free kind found in the web and in social networks? Quotation withheld because this record is not cleared for redistribution. Shows that metabolic networks in all three domains of life are scale-free, and that their diameter is conserved across organisms of very different complexity - a property the non-biological scale-free networks do not have. Quotation withheld because this record is not cleared for redistribution. existence Quotation withheld because this record is not cleared for redistribution. large-scale topology of metabolic networks Quotation withheld because this record is not cleared for redistribution. network-analysis network-analysis Quotation withheld because this record is not cleared for redistribution. mechanisms growth with preferential attachment: new nodes join by attaching to already well connected ones, which is what produces the power law Quotation withheld because this record is not cleared for redistribution. mechanisms hub dominance: a few highly connected substrates carry the connectivity, so removing them raises the diameter sharply and breaks the network into isolated clusters Quotation withheld because this record is not cleared for redistribution. mechanisms error tolerance: because most substrates are sparsely connected, removing random ones leaves the average distance unchanged Quotation withheld because this record is not cleared for redistribution. mechanisms increasing per-substrate connectivity is what holds the diameter constant as organisms get more complex Quotation withheld because this record is not cleared for redistribution. Eighteen of the 43 organisms are not fully sequenced and many ORFs are functionally unassigned, so the substrate and reaction lists analysed are incomplete. what this limits: the substrate and reaction lists every topology statistic is computed over: 18 OF THE 43 ORGANISMS ... ARE NOT YET FULLY SEQUENCED, AND A SUBSTANTIAL PORTION OF THE IDENTIFIED ORFs ARE FUNCTIONALLY UNASSIGNED Quotation withheld because this record is not cleared for redistribution. The extension of the conclusion to non-metabolic cellular networks is only preliminary, because those networks are too small for unambiguous statistical analysis with current tools. what this limits: the extension beyond metabolism: OUR PRELIMINARY ANALYSIS SUGGEST[s] THAT CONNECTIVITY DISTRIBUTION OF NON-METABOLIC PATHWAYS ALSO FOLLOWS A POWER-LAW - preliminary, and by the authors' own account not statistically decidable Quotation withheld because this record is not cleared for redistribution. 18 of the 43 organisms were not fully sequenced and many ORFs are unassigned, so the substrate and reaction lists are known to be incomplete. what this limits: the same scope as limitations[0] - the enzyme list is incomplete by construction Quotation withheld because this record is not cleared for redistribution. The generalisation to other cellular networks is explicitly not supported - those networks are too small for the statistics to be unambiguous. what this limits: the same scope as limitations[1], with the reason: THE CURRENT MATHEMATICAL TOOLS DO NOT ALLOW UNAMBIGUOUS STATISTICAL ANALYSIS OF THE TOPOLOGY OF OTHER NETWORKS DUE TO THEIR RELATIVELY SMALL SIZE Quotation withheld because this record is not cleared for redistribution. The whole analysis rests on one predicted database, whose pathways are inferred from annotated genomes rather than observed. what this limits: the object the whole analysis is about: THIS INTEGRATED PATHWAY-GENOME DATABASE PREDICTS THE EXISTENCE OF A GIVEN METABOLIC PATHWAY BASED ON THE ANNOTATED GENOME OF AN ORGANISM, so the network is inferred rather than measured Quotation withheld because this record is not cleared for redistribution. applying complex-network (scale-free) analysis to the large-scale organization of cellular metabolism Quotation withheld because this record is not cleared for redistribution. the metabolic network topology tested against the inherently random and uniform exponential model as the alternative description eliminates: a scale-free reading of a network that a random model would fit just as well - the paper sets up the exponential model as the thing to rule out before claiming anything else · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. scale-free network scale-free network Quotation withheld because this record is not cleared for redistribution. metabolic network metabolic network Quotation withheld because this record is not cleared for redistribution. node node Quotation withheld because this record is not cleared for redistribution. substrate substrate Quotation withheld because this record is not cleared for redistribution. link link Quotation withheld because this record is not cleared for redistribution. metabolic reactions metabolic reactions Quotation withheld because this record is not cleared for redistribution. exponential networks exponential networks Quotation withheld because this record is not cleared for redistribution. hubs hubs Quotation withheld because this record is not cleared for redistribution. network diameter network diameter Quotation withheld because this record is not cleared for redistribution. biochemical pathway biochemical pathway Quotation withheld because this record is not cleared for redistribution. small-world character small-world character Quotation withheld because this record is not cleared for redistribution. network - a metabolic network, where the nodes are chemical substrates and the links are the reactions between them Quotation withheld because this record is not cleared for redistribution. network - the World-Wide Web, the Internet and social networks, cited as the systems where this structure was first reported Quotation withheld because this record is not cleared for redistribution. path - in a metabolic network a path is a biochemical pathway, the chain of reactions from one substrate to another Quotation withheld because this record is not cleared for redistribution. claim_type: existence a second reading reaching the same value. Recorded: existence — note: a second reading reaching the same value from a different sentence. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. method: comparative a second reading. Recorded: network-analysis — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. phenomenon: scale-free topology of metabolic networks, with a network diameter conserved across organisms a second reading. Recorded: large-scale topology of metabolic networks — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. builds-on → scale-free network theory Quotation withheld because this record is not cleared for redistribution. contradicts → the expectation that network diameter grows with organism complexity Quotation withheld because this record is not cleared for redistribution. extends → the scale-free / error-tolerant network framework of Barabasi and co-workers (refs 2, 5) Quotation withheld because this record is not cleared for redistribution. contradicts → the expectation from previously examined non-biological networks (refs 2, 27, 28) that network diameter grows with the number of nodes Quotation withheld because this record is not cleared for redistribution. builds-on → barabasi-albert1999-scale-free - growth with preferential attachment Quotation withheld because this record is not cleared for redistribution. extends → the scale-free findings for the World-Wide Web, the Internet and social networks Quotation withheld because this record is not cleared for redistribution. contradicts → the Erdos-Renyi random network model as a description of cellular networks Quotation withheld because this record is not cleared for redistribution. node —renamed-across-fields→ substrate node substrate strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. link —renamed-across-fields→ metabolic reactions link metabolic reactions strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. metabolic network —is-a→ scale-free network metabolic network scale-free network strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. scale-free network —contrasted-with→ exponential networks scale-free network exponential networks differs in: THE AXIS IS DEGREE HETEROGENEITY. 'Quotation withheld.' Both are networks and both have degree distributions; the contrast is on the SHAPE of that distribution, which is the only property at issue. · strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. EVIDENCE CORRECTED (RE-GROUNDED) · hubs —part-of→ scale-free network hubs scale-free network EVIDENCE CORRECTED: RE-GROUNDED. The old span named only one endpoint. This sentence names both and places the hubs inside the network's topology, which is the containment the edge records. — strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. hubs —causes→ network diameter hubs network diameter strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its span and kept, but the span says removing hubs raises the diameter; the edge omits the removal. Quotation withheld because this record is not cleared for redistribution. 43 — metabolic networks compared, spanning all three domains of life Quotation withheld because this record is not cleared for redistribution. P(k) ~ k^-γ — scale-free power-law degree distribution of metabolic networks Quotation withheld because this record is not cleared for redistribution. 43 organisms — size of the comparative sample, spanning all three domains of life Quotation withheld because this record is not cleared for redistribution. γin = 2.2 — power-law exponent for incoming links in E. coli Quotation withheld because this record is not cleared for redistribution. ~4% — share of substrates present in every one of the 43 organisms Quotation withheld because this record is not cleared for redistribution. 51 substrates — the substrates present in all 43 organisms, used for the rank-order analysis Quotation withheld because this record is not cleared for redistribution. 6 archaea, 32 bacteria, 5 eukaryota — composition of the sample Quotation withheld because this record is not cleared for redistribution. Metabolic networks display the same topologic scaling properties, strikingly similar to the organization of complex non-biological systems. Quotation withheld because this record is not cleared for redistribution. This suggests that metabolic organization is identical for all living organisms and complies with the design principles of robust and error-tolerant scale-free networks. about this quote: QUOTE REPAIRED: the extractor split a hyphen-space and the quote was recorded faithfully with the damage in it, which made it unanchorable. The repaired string is an EXACT SUBSTRING of the staged text - that is why it was accepted, not because a rule produced it. The text as originally recorded is kept in evidence as extracted. Quotation withheld because this record is not cleared for redistribution. Metabolic networks in all three domains of life are scale-free: the number of reactions a substrate takes part in follows a power law. Quotation withheld because this record is not cleared for redistribution. Metabolic-network diameter is identical across all 43 organisms, whatever their number of substrates. Quotation withheld because this record is not cleared for redistribution. The ranking of the most connected substrates is practically identical for all 43 organisms. Quotation withheld because this record is not cleared for redistribution. Removing randomly chosen substrates, mimicking random mutations, left the average distance between the remaining nodes unaffected: a striking insensitivity to random errors. Quotation withheld because this record is not cleared for redistribution. number of substrates number of substrates Quotation withheld because this record is not cleared for redistribution. network diameter network diameter Quotation withheld because this record is not cleared for redistribution. hubs hubs Quotation withheld because this record is not cleared for redistribution. metabolic network metabolic network Quotation withheld because this record is not cleared for redistribution. network diameter network diameter Quotation withheld because this record is not cleared for redistribution. ER model ER model Quotation withheld because this record is not cleared for redistribution. small-world character small-world character Quotation withheld because this record is not cleared for redistribution. standard-deviation standard-deviation Quotation withheld because this record is not cleared for redistribution. power-law power-law Quotation withheld because this record is not cleared for redistribution. poisson-distribution poisson-distribution Quotation withheld because this record is not cleared for redistribution. standard-deviation standard-deviation Quotation withheld because this record is not cleared for redistribution.

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