Dataset Information

MetaMapp: mapping and visualizing metabolomic data by integrating information from biochemical pathways and chemical and mass spectral similarity.

ABSTRACT:

Background

Exposure to environmental tobacco smoke (ETS) leads to higher rates of pulmonary diseases and infections in children. To study the biochemical changes that may precede lung diseases, metabolomic effects on fetal and maternal lungs and plasma from rats exposed to ETS were compared to filtered air control animals. Genome- reconstructed metabolic pathways may be used to map and interpret dysregulation in metabolic networks. However, mass spectrometry-based non-targeted metabolomics datasets often comprise many metabolites for which links to enzymatic reactions have not yet been reported. Hence, network visualizations that rely on current biochemical databases are incomplete and also fail to visualize novel, structurally unidentified metabolites.

Results

We present a novel approach to integrate biochemical pathway and chemical relationships to map all detected metabolites in network graphs (MetaMapp) using KEGG reactant pair database, Tanimoto chemical and NIST mass spectral similarity scores. In fetal and maternal lungs, and in maternal blood plasma from pregnant rats exposed to environmental tobacco smoke (ETS), 459 unique metabolites comprising 179 structurally identified compounds were detected by gas chromatography time of flight mass spectrometry (GC-TOF MS) and BinBase data processing. MetaMapp graphs in Cytoscape showed much clearer metabolic modularity and complete content visualization compared to conventional biochemical mapping approaches. Cytoscape visualization of differential statistics results using these graphs showed that overall, fetal lung metabolism was more impaired than lungs and blood metabolism in dams. Fetuses from ETS-exposed dams expressed lower lipid and nucleotide levels and higher amounts of energy metabolism intermediates than control animals, indicating lower biosynthetic rates of metabolites for cell division, structural proteins and lipids that are critical for in lung development.

Conclusions

MetaMapp graphs efficiently visualizes mass spectrometry based metabolomics datasets as network graphs in Cytoscape, and highlights metabolic alterations that can be associated with higher rate of pulmonary diseases and infections in children prenatally exposed to ETS. The MetaMapp scripts can be accessed at http://metamapp.fiehnlab.ucdavis.edu.

SUBMITTER: Barupal DK

PROVIDER: S-EPMC3495401 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MetaMapp: mapping and visualizing metabolomic data by integrating information from biochemical pathways and chemical and mass spectral similarity.

Barupal Dinesh K DK Haldiya Pradeep K PK Wohlgemuth Gert G Kind Tobias T Kothari Shanker L SL Pinkerton Kent E KE Fiehn Oliver O

BMC bioinformatics 20120516

<h4>Background</h4>Exposure to environmental tobacco smoke (ETS) leads to higher rates of pulmonary diseases and infections in children. To study the biochemical changes that may precede lung diseases, metabolomic effects on fetal and maternal lungs and plasma from rats exposed to ETS were compared to filtered air control animals. Genome- reconstructed metabolic pathways may be used to map and interpret dysregulation in metabolic networks. However, mass spectrometry-based non-targeted metabolomi ...[more]

PMID: 22591066

Similar Datasets

Project description:The urine metabolome constitutes a rich source of functional information reflecting physiological states that are influenced by distinct conditions and biological stresses, such as responses to drug treatments or disease manifestations. Although global liquid chromatography-mass spectrometry (MS) profiling provides the most comprehensive measurement of metabolites in complex biological samples, annotation remains a challenge, and computational approaches are necessary to translate the molecular composition into biological knowledge. Here, we investigated the use of tandem MS-based enhanced molecular networks (MolNetEnhancer) to improve the metabolite annotation of urine extracts. The samples (n = 10) were analyzed by hydrophilic interaction chromatography-quadrupole time-of-flight mass spectrometry in both electrospray ionization (ESI) modes. Consistent with other common data preprocessing software, the use of Progenesis QI led to the annotation of up to 20 metabolites based on MS2 library searches, showing a high fragmentation score (cosine similarity ≥ 0.7), that is, ∼2% of mass features containing MS2 spectra. Molecular networking based on library matching resulted in the annotation of up to 62 urinary compounds. Using a combination of unsupervised substructure discovery (MS2LDA), the in silico tool network annotation propagation (NAP), and ClassyFire chemical ontology, embedded in a multilayered molecular network by MolNetEnhancer, we were able to expand the chemical characterization to ∼50% of the data set. The integrative approach led to the annotation of 275 compounds at the metabolomics standards initiative (MSI) confidence level 2, as well as 459 and 578 urinary metabolites (MSI level 3) in both negative and positive ESI modes, respectively. The exhaustive MS2-based annotation outperformed similar studies applied to larger cohorts while offering the discovery of metabolites not identified by the MS2 library search. This is the first work that effectively integrates orthogonal annotation methods and MS2-based fragmentation studies to improve metabolite annotation in urine samples.

Dataset Information

MetaMapp: mapping and visualizing metabolomic data by integrating information from biochemical pathways and chemical and mass spectral similarity.

Background

Results

Conclusions

Publications

MetaMapp: mapping and visualizing metabolomic data by integrating information from biochemical pathways and chemical and mass spectral similarity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets