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1 : overbeek 1.1 <h1>Support for Metabolic Reconstructions in the NMPDR</h1>
2 :     by Ross Overbeek
3 :    
4 :     <h2>Introduction</h2>
5 :    
6 :     The term metabolic reconstruction was created by Evgeni Selkov to
7 :     describe his early efforts to predict the metabolic capabilities of
8 :     an organism from partially sequenced genomes. I remember discussing
9 :     this concept in some detail at least a year before the first
10 :     completely sequenced genome became available (he was working on
11 :     analysis of <i>Mycoplasma capricolum</i>, and organism that we thought
12 :     might become the first completely sequenced genome).
13 :     <p>
14 :     Since those early days, the concept has taken on a variety of more
15 :     specialized meanings. This was natural, since reconstruction of
16 :     metabolic networks was clearly an important topic, and many groups
17 :     have begun to address the problem. In the context of the NMPDR, we
18 :     distinguish two versions of metabolic reconstructions: informal
19 :     metabolic reconstructions and formal metabolic
20 :     reconstructions.
21 :     <p>
22 :     <h2>What Is an Informal Metabolic Reconstruction?</h2>
23 :    
24 :     An <b>informal metabolic reconstruction</b>, as we use the term,
25 :     describes
26 :    
27 :     <ul>
28 :     <li>
29 :     the set of pathways present in the organism,
30 :     <li>
31 :     the functional roles of each pathway that can be connected to specific
32 :     genes, and
33 :     <li>
34 :     the functional roles that are believed to be present, but which cannot
35 :     yet be connected to specific genes.
36 :     </ul>
37 :     <p>
38 :     Within <a href=./1KG.html>The Project to Annotate 1000 Genomes</a>,
39 :     the notion of pathway was generalized to <b>subsystem</b>. Subsystems
40 :     can be pathways, but they could also be a collection of functional
41 :     roles that implement a nonmetabolic process. A subsystem is given a
42 :     fairly abstract definition -- it is simply a set of functional roles.
43 :     Hence, an informal metabolic reconstruction for an organism amounts to
44 :     a set of subsystems that are believed to be present (actually, we
45 :     specifiy which of several possible <i>variants</i> of each subsystem
46 :     is present), the functional roles that make up these subsystems, and
47 :     how those functional roles connect to genes.
48 :     <p>
49 :     <h2>A Specific Informal Metabolic Reconstruction</h2>
50 :    
51 :     It is, perhaps, easier if we consider an example: go to the home page
52 :     of the NMPDR, click on <b>Subsystem Summary</b>, select an organism
53 :     (say, <i>Staphylococcus aureus subsp. aureus MRSA252</i>), and click
54 :     on <b>Show Subsystems</b>. Now look carefully at what is displayed:
55 :    
56 :     <ul>
57 :     <li>
58 :     There are some main sections headers like <b>Amino Acids and
59 :     Derivatives</b>. Sometimes, there are second-level breakdowns in this
60 :     minimal classification such as <b>Alanine, serine, and glycine</b>.
61 :     The classification framework at this point is pretty minimal.
62 :     <li>
63 :     Within classification sections, there are subsystems like
64 :     <b>Arginine_Putrescine_and_4-aminobutyrate_degradation</b>,
65 :     <b>Asp-Glu-tRNA(Asn-Gln)_transamidation</b>, and so forth. Links from
66 :     to the routines to display the details of each subsystem can be
67 :     followed to see what funcgtional roles are included, who constructed
68 :     it, how the genes cluster on different chromosomes, and so forth.
69 :     <li>
70 :     Below the name of each subsystem, we include the genes that have been
71 :     connected to roles from the subsystem. You can explore the individual
72 :     genes by taking the provided links.
73 :     </ul>
74 :     <br>
75 :     In the context of the NMPDR, this is what we mean by an informal
76 :     metabolic reconstruction. This basic information becomes the
77 :     underlying data from which specific properties of the organism can be
78 :     predicted. One specific goal of gthe NMPDR is to make these informal
79 :     metabolic reconstructions as comprehensive as possible.
80 :    
81 :     <h2>What Is a Formal Reconstructions?</h2>
82 :    
83 :     By the term <b>formal metabolic reconstruction</b> we mean a detailed
84 :     encoding of the metabolic reaction network. There are different
85 :     possible representations that might be chosen, but they are all
86 :     equivalent. One must represent the reactions that the organism might
87 :     support. For each reaction, one must include the substrates and
88 :     products, whether or not the reaction is reversible, the enzymatic
89 :     function that catalyzes the reaction, and which proteins in the
90 :     organism implement the enzymatic role.
91 :     <p>
92 :     Again, let us consider an example: go to the home page
93 :     of the NMPDR, click on <b>Subsystem Summary</b>, select an organism
94 :     (say, <i>Staphylococcus aureus subsp. aureus MRSA252</i>), and click
95 :     on <b>Show Reactions</b>. In this display, you see the reactions, and
96 :     by clicking on the link you will be able to go to KEGG for a more
97 :     detailed depiction of the reaction.
98 :     <p>
99 :     A formal reconstruction represents the starting point for modeling
100 :     efforts. Our goal at the NMPDR is to make our compilations of
101 :     reactions for each organism easily accessible, to maintain links to
102 :     KEGG (which offers an excellent encoding of reactions and compounds, as
103 :     well as metabolic reconstructions).
104 :     <p>
105 :     It should be noted that our initial offerings represent starting
106 : golsen 1.2 points that we intend to constantly improve.

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