Identifying similarities at metabolic pathways with a strategy of Enzymatic Step Sequences

Augusto Cesar Poot-Hernandez; Katya Rodriguez-Vazquez; Ernesto Perez-Rueda

doi:10.1016/j.mex.2023.102118

Identifying similarities at metabolic pathways with a strategy of Enzymatic Step Sequences

MethodsX. 2023 Mar 11:10:102118. doi: 10.1016/j.mex.2023.102118. eCollection 2023.

Authors

Augusto Cesar Poot-Hernandez¹, Katya Rodriguez-Vazquez², Ernesto Perez-Rueda³

Affiliations

¹ Unidad de Bioinformática y Manejo de la Información. Instituto de Fisiología Celular. Universidad Nacional Autónoma de México, Ciudad Universitaria, México, Mexico.
² Departamento de Ingeniería de Sistemas Computacionales y Automatización, Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Ciudad Universitaria, México, Mexico.
³ Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Unidad Académica del Estado de Yucatán. Mérida, Yucatán. Mexico.

Abstract

An easy and fast strategy to compare functionally the metabolic maps is described. The KEGG metabolic maps are transformed into linear Enzymatic Step Sequences (ESS) using the Breadth First Search (BFS) algorithm. To do this, the KGML files are retrieved, and directed graph representations are created; where the nodes represent enzymes or enzymatic complexes, and the edges represent a compound, that is the 'product' from one reaction and a 'substrate' for the next. Then, a set of initialization nodes are selected, and used as the root for the construction of the BFS tree. This tree is used as a guide to the construction of the ESS. From each leaf (terminal node), the path is traced backwards until it reaches the root metabolic map and with two or fewer neighbors in the graph. In a second step, the ESS are compared with a Dynamic Programing algorithm, considering an "ad hoc" substitution matrix, and minimizing the global score. The dissimilarity values between two EC numbers ranged from 0 to 1, where 0 indicates similar EC numbers, and 1 indicates different EC numbers. Finally, the alignment is evaluated by using the normalized entropy-based function, considering a threshold of ≤ 0.27 as significant.•The KEGG metabolic maps are transformed into linear Enzymatic Step Sequences (ESS) using the Breadth First Search (BFS) algorithm.•Nodes represent enzymes or enzymatic complexes, and the edges represent a compound, that is 'product' from one reaction and a 'substrate' for the next.•The ESS are compared with a Dynamic Programing algorithm, considering an "ad hoc" substitution matrix, and minimizing the global score.

Keywords: Comparative genomics; Enzymatic Step Sequences (ESS) comparative program; Enzymatic step sequences; Enzyme commission number; KEGG; Metabolic pathways.