Enzyme sequence similarity improves the reaction alignment method for cross-species pathway comparison

Meric A. Ovacik, Ioannis Androulakis

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Pathway-based information has become an important source of information for both establishing evolutionary relationships and understanding the mode of action of a chemical or pharmaceutical among species. Cross-species comparison of pathways can address two broad questions: comparison in order to inform evolutionary relationships and to extrapolate species differences used in a number of different applications including drug and toxicity testing. Cross-species comparison of metabolic pathways is complex as there are multiple features of a pathway that can be modeled and compared. Among the various methods that have been proposed, reaction alignment has emerged as the most successful at predicting phylogenetic relationships based on NCBI taxonomy. We propose an improvement of the reaction alignment method by accounting for sequence similarity in addition to reaction alignment method. Using nine species, including human and some model organisms and test species, we evaluate the standard and improved comparison methods by analyzing glycolysis and citrate cycle pathways conservation. In addition, we demonstrate how organism comparison can be conducted by accounting for the cumulative information retrieved from nine pathways in central metabolism as well as a more complete study involving 36 pathways common in all nine species. Our results indicate that reaction alignment with enzyme sequence similarity results in a more accurate representation of pathway specific cross-species similarities and differences based on NCBI taxonomy.

Original languageEnglish (US)
Pages (from-to)363-371
Number of pages9
JournalToxicology and Applied Pharmacology
Volume271
Issue number3
DOIs
StatePublished - Sep 15 2013

Fingerprint

Taxonomies
Enzymes
Pharmacologic Actions
Glycolysis
Metabolic Networks and Pathways
Drug-Related Side Effects and Adverse Reactions
Metabolism
Citric Acid
Pharmaceutical Preparations
Toxicity
Conservation
Testing

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Keywords

  • Cross-species comparison
  • Metabolic pathways
  • Phylogenomics

Cite this

@article{c9e0eef870dd437b8a7f6b4120b40453,
title = "Enzyme sequence similarity improves the reaction alignment method for cross-species pathway comparison",
abstract = "Pathway-based information has become an important source of information for both establishing evolutionary relationships and understanding the mode of action of a chemical or pharmaceutical among species. Cross-species comparison of pathways can address two broad questions: comparison in order to inform evolutionary relationships and to extrapolate species differences used in a number of different applications including drug and toxicity testing. Cross-species comparison of metabolic pathways is complex as there are multiple features of a pathway that can be modeled and compared. Among the various methods that have been proposed, reaction alignment has emerged as the most successful at predicting phylogenetic relationships based on NCBI taxonomy. We propose an improvement of the reaction alignment method by accounting for sequence similarity in addition to reaction alignment method. Using nine species, including human and some model organisms and test species, we evaluate the standard and improved comparison methods by analyzing glycolysis and citrate cycle pathways conservation. In addition, we demonstrate how organism comparison can be conducted by accounting for the cumulative information retrieved from nine pathways in central metabolism as well as a more complete study involving 36 pathways common in all nine species. Our results indicate that reaction alignment with enzyme sequence similarity results in a more accurate representation of pathway specific cross-species similarities and differences based on NCBI taxonomy.",
keywords = "Cross-species comparison, Metabolic pathways, Phylogenomics",
author = "Ovacik, {Meric A.} and Ioannis Androulakis",
year = "2013",
month = "9",
day = "15",
doi = "10.1016/j.taap.2010.09.009",
language = "English (US)",
volume = "271",
pages = "363--371",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "3",

}

Enzyme sequence similarity improves the reaction alignment method for cross-species pathway comparison. / Ovacik, Meric A.; Androulakis, Ioannis.

In: Toxicology and Applied Pharmacology, Vol. 271, No. 3, 15.09.2013, p. 363-371.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Enzyme sequence similarity improves the reaction alignment method for cross-species pathway comparison

AU - Ovacik, Meric A.

AU - Androulakis, Ioannis

PY - 2013/9/15

Y1 - 2013/9/15

N2 - Pathway-based information has become an important source of information for both establishing evolutionary relationships and understanding the mode of action of a chemical or pharmaceutical among species. Cross-species comparison of pathways can address two broad questions: comparison in order to inform evolutionary relationships and to extrapolate species differences used in a number of different applications including drug and toxicity testing. Cross-species comparison of metabolic pathways is complex as there are multiple features of a pathway that can be modeled and compared. Among the various methods that have been proposed, reaction alignment has emerged as the most successful at predicting phylogenetic relationships based on NCBI taxonomy. We propose an improvement of the reaction alignment method by accounting for sequence similarity in addition to reaction alignment method. Using nine species, including human and some model organisms and test species, we evaluate the standard and improved comparison methods by analyzing glycolysis and citrate cycle pathways conservation. In addition, we demonstrate how organism comparison can be conducted by accounting for the cumulative information retrieved from nine pathways in central metabolism as well as a more complete study involving 36 pathways common in all nine species. Our results indicate that reaction alignment with enzyme sequence similarity results in a more accurate representation of pathway specific cross-species similarities and differences based on NCBI taxonomy.

AB - Pathway-based information has become an important source of information for both establishing evolutionary relationships and understanding the mode of action of a chemical or pharmaceutical among species. Cross-species comparison of pathways can address two broad questions: comparison in order to inform evolutionary relationships and to extrapolate species differences used in a number of different applications including drug and toxicity testing. Cross-species comparison of metabolic pathways is complex as there are multiple features of a pathway that can be modeled and compared. Among the various methods that have been proposed, reaction alignment has emerged as the most successful at predicting phylogenetic relationships based on NCBI taxonomy. We propose an improvement of the reaction alignment method by accounting for sequence similarity in addition to reaction alignment method. Using nine species, including human and some model organisms and test species, we evaluate the standard and improved comparison methods by analyzing glycolysis and citrate cycle pathways conservation. In addition, we demonstrate how organism comparison can be conducted by accounting for the cumulative information retrieved from nine pathways in central metabolism as well as a more complete study involving 36 pathways common in all nine species. Our results indicate that reaction alignment with enzyme sequence similarity results in a more accurate representation of pathway specific cross-species similarities and differences based on NCBI taxonomy.

KW - Cross-species comparison

KW - Metabolic pathways

KW - Phylogenomics

UR - http://www.scopus.com/inward/record.url?scp=84883743186&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883743186&partnerID=8YFLogxK

U2 - 10.1016/j.taap.2010.09.009

DO - 10.1016/j.taap.2010.09.009

M3 - Article

C2 - 20851138

AN - SCOPUS:84883743186

VL - 271

SP - 363

EP - 371

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 3

ER -