Support for Metabolic Reconstructions in the NMPDR

by Ross Overbeek

Introduction

The term metabolic reconstruction was created by Evgeni Selkov to describe his early efforts to predict the metabolic capabilities of an organism from partially sequenced genomes. I remember discussing this concept in some detail at least a year before the first completely sequenced genome became available (he was working on analysis of Mycoplasma capricolum, and organism that we thought might become the first completely sequenced genome).

Since those early days, the concept has taken on a variety of more specialized meanings. This was natural, since reconstruction of metabolic networks was clearly an important topic, and many groups have begun to address the problem. In the context of the NMPDR, we distinguish two versions of metabolic reconstructions: informal metabolic reconstructions and formal metabolic reconstructions.

What Is an Informal Metabolic Reconstruction?

An informal metabolic reconstruction, as we use the term, describes

Within The Project to Annotate 1000 Genomes, the notion of pathway was generalized to subsystem. Subsystems can be pathways, but they could also be a collection of functional roles that implement a nonmetabolic process. A subsystem is given a fairly abstract definition -- it is simply a set of functional roles. Hence, an informal metabolic reconstruction for an organism amounts to a set of subsystems that are believed to be present (actually, we specifiy which of several possible variants of each subsystem is present), the functional roles that make up these subsystems, and how those functional roles connect to genes.

A Specific Informal Metabolic Reconstruction

It is, perhaps, easier if we consider an example: go to the home page of the NMPDR, click on Subsystem Summary, select an organism (say, Staphylococcus aureus subsp. aureus MRSA252), and click on Show Subsystems. Now look carefully at what is displayed:
In the context of the NMPDR, this is what we mean by an informal metabolic reconstruction. This basic information becomes the underlying data from which specific properties of the organism can be predicted. One specific goal of gthe NMPDR is to make these informal metabolic reconstructions as comprehensive as possible.

What Is a Formal Reconstructions?

By the term formal metabolic reconstruction we mean a detailed encoding of the metabolic reaction network. There are different possible representations that might be chosen, but they are all equivalent. One must represent the reactions that the organism might support. For each reaction, one must include the substrates and products, whether or not the reaction is reversible, the enzymatic function that catalyzes the reaction, and which proteins in the organism implement the enzymatic role.

Again, let us consider an example: go to the home page of the NMPDR, click on Subsystem Summary, select an organism (say, Staphylococcus aureus subsp. aureus MRSA252), and click on Show Reactions. In this display, you see the reactions, and by clicking on the link you will be able to go to KEGG for a more detailed depiction of the reaction.

A formal reconstruction represents the starting point for modeling efforts. Our goal at the NMPDR is to make our compilations of reactions for each organism easily accessible, to maintain links to KEGG (which offers an excellent encoding of reactions and compounds, as well as metabolic reconstructions).

It should be noted that our initial offerings represent starting points that we intend to constantly improve.