Comparative genome-scale reconstruction of gapless metabolic networks for present and ancestral species

Autor: Paula Jouhten, Muhammad Fahad Syed, Jana Kludas, Merja Oja, Juho Rousu, Merja Penttilä, Peter Blomberg, Liisa Holm, Mikko Arvas, Esa Pitkänen, Jian Hou
Přispěvatelé: Aalto-yliopisto, Aalto University, Research Programs Unit, Department of Computer Science, Genome-Scale Biology (GSB) Research Program, Department of Medical and Clinical Genetics, Biosciences, Genetics, Institute of Biotechnology, Bioinformatics, Computational genomics
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Aspergillus Nidulans
Proteomics
Metabolic network
Yeast and Fungal Models
FLUX-BALANCE ANALYSIS
Genome
ANNOTATION
Biochemistry
Schizosaccharomyces Pombe
Gene Knockout Techniques
Biomass
ta518
Biology (General)
ta515
Phylogeny
Genetics
Kluyveromyces Lactis
Ecology
ta213
Systems Biology
Flux balance analysis
Enzymes
Computational Theory and Mathematics
Modeling and Simulation
Genome
Fungal

Sequence Analysis
Algorithms
Metabolic Networks and Pathways
COMMUNITY APPROACH
Research Article
Biotechnology
Genome evolution
QH301-705.5
Systems biology
education
Computational biology
DRUG TARGETS
Saccharomyces cerevisiae
Biology
Models
Biological

Ustilago Maydis
Evolution
Molecular

Cellular and Molecular Neuroscience
Metabolic Networks
Industrial Microbiology
Model Organisms
Exponential growth
Species Specificity
Candida Albicans
Molecular Biology
Ecology
Evolution
Behavior and Systematics

Comparative genomics
ta113
ta112
Models
Statistical

Models
Genetic

Fungi
PATHWAYS
Computational Biology
Neurospora Crassa
113 Computer and information sciences
Metabolism
Small Molecules
ta5141
Computer Science
3111 Biomedicine
Gene Function
Flux (metabolism)
Zdroj: PLoS Computational Biology, Vol 10, Iss 2, p e1003465 (2014)
PLoS Computational Biology
Pitkänen, E, Jouhten, P, Hou, J, Syed, M F, Blomberg, P, Kludas, J, Oja, M, Holm, L, Penttilä, M, Rousu, J & Arvas, M 2014, ' Comparative Genome-Scale Reconstruction of Gapless Metabolic Networks for Present and Ancestral Species ', PLoS Computational Biology, vol. 10, no. 2, e1003465 . https://doi.org/10.1371/journal.pcbi.1003465
ISSN: 1553-7358
DOI: 10.1371/journal.pcbi.1003465
Popis: We introduce a novel computational approach, CoReCo, for comparative metabolic reconstruction and provide genome-scale metabolic network models for 49 important fungal species. Leveraging on the exponential growth in sequenced genome availability, our method reconstructs genome-scale gapless metabolic networks simultaneously for a large number of species by integrating sequence data in a probabilistic framework. High reconstruction accuracy is demonstrated by comparisons to the well-curated Saccharomyces cerevisiae consensus model and large-scale knock-out experiments. Our comparative approach is particularly useful in scenarios where the quality of available sequence data is lacking, and when reconstructing evolutionary distant species. Moreover, the reconstructed networks are fully carbon mapped, allowing their use in 13C flux analysis. We demonstrate the functionality and usability of the reconstructed fungal models with computational steady-state biomass production experiment, as these fungi include some of the most important production organisms in industrial biotechnology. In contrast to many existing reconstruction techniques, only minimal manual effort is required before the reconstructed models are usable in flux balance experiments. CoReCo is available at http://esaskar.github.io/CoReCo/.
Author Summary Advances in next-generation sequencing technologies are revolutionizing molecular biology. Sequencing-enabled cost-effective characterization of microbial genomes is a particularly exciting development in metabolic engineering. There, considerable effort has been put to reconstructing genome-scale metabolic networks that describe the collection of hundreds to thousands of biochemical reactions available for a microbial cell. These network models are instrumental in understanding microbial metabolism and guiding metabolic engineering efforts to improve biochemical yields. We have developed a novel computational method, CoReCo, which bridges the growing gap between the availability of sequenced genomes and respective reconstructed metabolic networks. The method reconstructs genome-scale metabolic networks simultaneously for related microbial species. It utilizes the available sequencing data from these species to correct for incomplete and missing data. We used the method to reconstruct metabolic networks for a set of 49 fungal species providing the method protein sequence data and a phylogenetic tree describing the evolutionary relationships between the species. We demonstrate the applicability of the method by comparing a metabolic reconstruction of Saccharomyces cerevisiae to the manually curated, high-quality consensus network. We also provide an easy-to-use implementation of the method, usable both in single computer and distributed computing environments.
Databáze: OpenAIRE