SEAS: a system for SEED-based pathway enrichment analysis

Abstract

Pathway enrichment analysis represents a key technique for analyzing high-throughput omic data, and it can help to link individual genes or proteins found to be differentially expressed under specific conditions to well-understood biological pathways. We present here a computational tool, SEAS, for pathway enrichment analysis over a given set of genes in a specified organism against the pathways (or subsystems) in the SEED database, a popular pathway database for bacteria. SEAS maps a given set of genes of a bacterium to pathway genes covered by SEED through gene ID and/or orthology mapping, and then calculates the statistical significance of the enrichment of each relevant SEED pathway by the mapped genes. Our evaluation of SEAS indicates that the program provides highly reliable pathway mapping results and identifies more organism-specific pathways than similar existing programs. SEAS is publicly released under the GPL license agreement and freely available at http://csbl.bmb.uga.edu/~xizeng/research/seas/.

Figure 1. A schematic representation of the SEAS workflow.

Each rectangle represents a program, each cylinder represents a database, and the others are flat text files for input, output or intermediate results.

Figure 2. SEAS-based re-annotation of E. coli pathways using 11 reference genomes.

(A) Taxonomic distance between reference genomes and E. coli. The first column represents the reference genomes, used in the x-axis in (B)–(D); (B) Re-annotation of E. coli pathways using the single genome strategy; (C) Re-annotation of E. coli pathways using the multiple genome strategy #1; (D) Re-annotation of E. coli pathways using the multiple genome strategy #2.

Figure 3. SEAS-based re-annotation of B. subtilis pathways using 11 reference genomes.

(A) Taxonomic distance between reference genomes and B. subtilis. The first column represents the reference genomes, which are used in the x-axis in (B)–(D); (B) Re-annotation of B. subtilis pathways using the single genome strategy; (C) Re-annotation of B. subtilis pathways using the multiple genome strategy #1; (D) Re-annotation of B.subtilis pathways using the multiple genome strategy #2. L. sphaericus is very low in panel B at position 4 on the x-axis as it has no pathway annotation information.