Manual

MetaPath : Metabolic Pathway Analysis Tool

1. Introduction

Genomic sequencing information makes it possible to reconstruct genome-specific metabolic network. These networks are often very large and complex. To properly understand and analyze the global properties of metabolic networks, methods for rationally representing and quantitatively analyzing their structure are needed.

MetaPath is a metabolic pathway analysis tool. It combines KEGG's the metabolic pathway information a and GenBank's equence information to reconstruct metablolic pathways among the selected genomes. I It provides users with flexibility in choosing the genomes and metabolic pathways of their interest and performs the sequence analysis on the selected pathways and genomes using tools such as FASTA and HMMER.

This tool aims to find missing metabolic pathways by comparing reference genome with a set of genome selection. The result is represented as a table, but the directionality of metabolic pathway is not considered at this stage because of the lack of such information in KEGG database. In table, each plausible missing component is represented as a quotation mark. In most case, such a protein is a hypothetical protein, whose biological function is not reported yet, or has a low sequence similarity with other metabolic pathway components in the same column at a given Z-score. A simple experiment with HMMER can be done to automatically search sequence motif to predict plausible function of this hypothetical protein. Users may get more components by setting lower Z-score (Default value is 300). MetaPath web service is limited to only prokaryotic genomes because of the limitation of KEGG database.

2. How to Use ?

Fig 1. MetaPath Interface

At the frontpage, you may choose reference genome, multiple genomes, and metabolic pathway(s). you may upload a sequence file instead of choosing metabolic pathways. In this case, MetaPath will search all possible metabolic pathways found in reference genome.

Fig 2. Metapath Result

MetaPath prints simple information regarding to reference genome, multiple genomes, and metabolic pathways chosen by you.

Fig 3. Tabular Presentation of Metabolic Components

Metabolic component table is automatically generated and reference genome is used as a backbone of reconstructed metabolic pathways of other genomes. A question mark stands for a pathway component (protein) that is missing a given genome, but found in a metabolic pathway of the reference genome. Default Z-score is 300, but you may increase or decrease Z-score by click +/- button on the top. Components are indicated by GI numbers and you may refer to more information about these proteins by clicking GI numbers. With lower Z-score, you will get less missing components.

Fig 4. HMMer search result

You may also build Hidden Markov Model to identify missing components. HMMER result is printed on screen when a question mark is clicked. But finding homolog does not always mean that this is a "REAL" metabolic component. But this information can be used as a good reference to reconstruct an incomplete metabolic pathway information in KEGG or other pathway Database.

Fig 5. Metabolic Pathway Diagram from KEGG

Kwangmin Choi @ School of Informatics, Indiana University, Bloomington, IN, USA
Last Updated on 8/1/2004