Volume 15 Supplement 3

Highlights from the Ninth International Society for Computational Biology (ISCB) Student Council Symposium 2013

Open Access

An integrated approach to understand apicomplexan metabolism from their genomes

  • Achchuthan Shanmugasundram1, 2Email author,
  • Faviel F Gonzalez-Galarza1,
  • Jonathan M Wastling2,
  • Olga Vasieva1 and
  • Andrew R Jones1
BMC Bioinformatics201415(Suppl 3):A3

DOI: 10.1186/1471-2105-15-S3-A3

Published: 11 February 2014

Background

The Apicomplexa is a large phylum of intracellular parasites that show great diversity and adaptability in the various ecological niches they occupy. They are the causative agents of human and animal infections including malaria, toxoplasmosis and theileriosis, which have a huge economic and social impact. A number of apicomplexan genomes have been sequenced and are publicly available. However, the prediction of gene models and annotation of gene functions remains challenging.

Methods

We have utilised an approach called ‘metabolic reconstruction’, in which genes are systematically assigned to functions within pathways/networks [14]. Functional annotation and metabolic reconstruction was carried out using a semi-automatic approach, integrating genomic information with biochemical evidence from the literature. The functions were automatically assigned using a sequence similarity-based approach and protein motif information. Experimental evidence was also accommodated in the confirmation of functions and the grouping of genes into metabolic pathways.

Results

A web database named Library of Apicomplexan Metabolic Pathways (LAMP, http://www.llamp.net) [5] was developed to deposit the reconstructed metabolic pathways of Toxoplasma gondii, Neospora caninum, Cryptosporidium and Theileria species and Babesia bovis. Each metabolic pathway page contains an interactive metabolic pathway map, gene annotations hyperlinked to external resources and detailed information about the metabolic capabilities. This analysis led to the identification of missing enzymes that must be present to complete the metabolic pathway and orphan genes (incorrect enzyme annotations or enzymes that are involved in salvage of metabolites) that are isolated in pathways that are otherwise absent. The compilation and annotation of metabolic pathways and the comparative analysis of the overall metabolic capabilities of apicomplexan species enabled identification of differences in their ability to synthesise or depend on hosts for several metabolites (Table 1, Additional file 1).
Table 1

A survey of the data available for the different apicomplexan genomes in LAMP. The analysis is updated from the survey table published in the previous publication [5]

Organism

No of metabolic pathways

No of unique enzymesa

No of missing enzymesb

No of reactionsc

Total no of metabolitesd

No of metabolites from hoste

No of end metabolites to host or of unknown fatef

T. gondii

51

419

17

509

500

41

23

N. caninum

51

412

23

509

500

41

23

C. muris

31

224

15

255

281

32

7

C. parvum

28

207

10

231

261

31

8

C. hominis

28

200

17

230

261

31

8

T. parva

32

213

17

234

258

26

9

T. annulata

32

214

16

235

258

26

9

B. bovis

32

216

11

233

256

26

9

a Unique Enzymes represent total unique enzyme activities (enzymes with full, partial and no EC numbers) annotated to be present in the pathways for an organism.

b Missing enzymes represent the enzymes need to be present to complete the metabolic pathways. They may either be missing in the gene model predictions or may be absent in the organism.

c Total number of biochemical reactions annotated to metabolic pathways from KEGG REACTION database.

d Total number of metabolites annotated to metabolic pathways from KEGG COMPOUND and KEGG GLYCAN databases.

e Number of precursor metabolites in the metabolic pathways that are annotated to be obtained from host. This number does not include any other metabolites that are obtained from host and not part of any of the annotated pathways in LAMP.

f Number of end metabolites in the metabolic pathways that does not end up in a downstream pathway. These can either be metabolites that end up in host or the fate pathways are unknown.

Conclusions

The carefully annotated metabolic pathways and the comparative analysis of metabolism for eight apicomplexan species are publicly available for the research community in the LAMP database (http://www.llamp.net). This has improved the functional annotation immensely and led to identification of putative drug targets. The hyperlinks for LAMP metabolic pathway annotations are available from the respective gene pages of the T. gondii primary database, ToxoDB (release 9) [6], enabling a wider reach for LAMP.

Declarations

Acknowledgements

LAMP web database was already published in the database issue of Nucleic acids research (January 2013). LAMP is indirectly funded through several grants from Biotechnology and Biological Sciences Research Council. Travel expenses of AS to the ISCB Student Council Symposium was funded from the BBSRC DTG studentship awarded to the University of Liverpool.

Authors’ Affiliations

(1)
Institute of Integrative Biology, University of Liverpool
(2)
Institute of Infection and Global Health, University of Liverpool

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Copyright

© Shanmugasundram et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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