iPath: Interactive exploration of biochemical pathways and networks

EMBL, Meyerhofstrasse 1, Heidelberg, Germany.
Trends in Biochemical Sciences (Impact Factor: 11.23). 04/2008; 33(3):101-3. DOI: 10.1016/j.tibs.2008.01.001
Source: PubMed


iPath is an open-access online tool ( for visualizing and analyzing metabolic pathways. An interactive viewer provides straightforward navigation through various pathways and enables easy access to the underlying chemicals and enzymes. Customized pathway maps can be generated and annotated using various external data. For example, by merging human genome data with two important gut commensals, iPath can pinpoint the complementarity of the host-symbiont metabolic capacities.

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    • "GO annotations were then used in an enrichment analysis for biological processes, molecular function, and cellular components as implemented in GOrilla with a P-value threshold of 0.001 (Eden et al. 2009). Furthermore, we visualized metabolic pathways associated with shared differentially expressed genes through annotation with KEGG orthologs (Kyoto Encyclopedia of Genes and Genomes; Kanehisa et al. 2012) as implemented in iPath v2 (Letunic et al. 2008).Fig. 1. A. Primary enzymes involved in the oxidative phosphorylation pathway of the mitochondrial respiratory chain, which represents a nexus of H 2 S toxicity and detoxification. H 2 S is toxic because it blocks cytochrome c oxidase (COX; complex IV) of the respiratory chain. "
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    ABSTRACT: Hydrogen sulfide (H2S) is a potent toxicant interfering with oxidative phosphorylation in mitochondria and creating extreme environmental conditions in aquatic ecosystems. The mechanistic basis of adaptation to perpetual exposure to H2S remains poorly understood. We investigated evolutionarily independent lineages of livebearing fishes that have colonized and adapted to springs rich in H2S and compared their genome-wide gene expression patterns to closely related lineages from adjacent, nonsulfidic streams. Significant differences in gene expression were uncovered between all sulfidic and nonsulfidic population pairs. Variation in the number of differentially expressed genes among population pairs corresponded to differences in divergence times and rates of gene flow, which is consistent with neutral drift driving a substantial portion of gene expression variation among populations. Accordingly, there was little evidence for convergent evolution shaping large-scale gene expression patterns among independent sulfide spring populations. Nonetheless, we identified a small number of genes that was consistently differentially expressed in the same direction in all sulfidic and nonsulfidic population pairs. Functional annotation of shared differentially expressed genes indicated upregulation of genes associated with enzymatic H2S detoxification and transport of oxidized sulfur species, oxidative phosphorylation, energy metabolism, and pathways involved in responses to oxidative stress. Overall, our results suggest that modification of processes associated with H2S detoxification and toxicity likely complement each other to mediate elevated H2S tolerance in sulfide spring fishes. Our analyses allow for the development of novel hypotheses about biochemical and physiological mechanisms of adaptation to extreme environments.
    Full-text · Article · Feb 2016 · Molecular Biology and Evolution
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    • "c pathways was prominent in both between - and within - population contrasts , but under HiP , metabolic pathways were upregulated in A rela - tive to M genotypes . Pathways that were differentially regulated in at least one of the between - population contrasts ( Appendix S2 , Supporting information ) were combined for visualiza - tion in iPath ( Letunic et al . 2008 ) . This was carried out separately for the HiP and LoP treatments to identify potential functional relevance of differential regulation in response to P - supply ( Fig . 2A : HiP ; Fig . 2B : LoP ) . These pathways are expected to be particularly impor - tant because they underlie differential regulation between A and M genotypes , whi"
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    ABSTRACT: Little is known about the role of transcriptomic changes in driving phenotypic evolution in natural populations, particularly in response to anthropogenic environmental change. Previous analyses of Daphnia genotypes separated by centuries of evolution in a lake using methods in resurrection ecology revealed striking genetic and phenotypic shifts that were highly correlated with anthropogenic environmental change, specifically phosphorus (P)-driven nutrient-enrichment (i.e., eutrophication). Here, we compared the transcriptomes of two ancient (~700-yr-old) and two modern (~10-yr-old) genotypes in historic (low P) and contemporary (high P) environmental conditions using microarrays. We found considerable transcriptomic variation between ‘ancient’ and ‘modern’ genotypes in both treatments, with stressful (low P) conditions eliciting differential expression (DE) of a larger number of genes. Further, more genes were DE between ‘ancient’ and ‘modern’ genotypes than within these groups. Expression patterns of individual genes differed greatly among genotypes, suggesting that different transcriptomic responses can result in similar phenotypes. While this confounded patterns between ‘ancient’ and ‘modern’ genotypes at the gene level, patterns were discernible at the functional level: annotation of DE genes revealed particular enrichment of genes involved in metabolic pathways in response to P-treatments. Analyses of gene families suggested significant DE in pathways already known to be important in dealing with P-limitation in Daphnia as well as in other organisms. Such observations on genotypes of a single natural population, separated by thousands of generations of evolution in contrasting environmental conditions before and during anthropogenic environmental changes highlight the important role of transcriptional mechanisms in the evolutionary responses of populations.This article is protected by copyright. All rights reserved.
    Full-text · Article · Nov 2014 · Molecular Ecology
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    • "When available, COG assignment was performed using the Batch Web CD-Search online tool ( Predicted functions were projected on KEGG metabolic pathways using the Ipath software55 and compared to essential genes identified in the model organism Bacillus subtilis56. When species-level taxonomy could not be assigned, higher taxonomic levels were assigned using MEGAN57. "
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    ABSTRACT: The gut microbiota (GM) consists of resident commensals and transient microbes conveyed by the diet but little is known about the role of the latter on GM homeostasis. Here we show, by a conjunction of quantitative metagenomics, in silico genome reconstruction and metabolic modeling, that consumption of a fermented milk product containing dairy starters and Bifidobacterium animalis potentiates colonic short chain fatty acids production and decreases abundance of a pathobiont Bilophila wadsworthia compared to a milk product in subjects with irritable bowel syndrome (IBS, n = 28). The GM changes parallel improvement of IBS state, suggesting a role of the fermented milk bacteria in gut homeostasis. Our data challenge the view that microbes ingested with food have little impact on the human GM functioning and rather provide support for beneficial health effects.
    Full-text · Article · Sep 2014 · Scientific Reports
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