MBROLE 2.0—functional enrichment of chemical compounds

López-Ibáñez, Javier; Pazos, Florencio; Chagoyen, Mónica

doi:10.1093/nar/gkw253

Cited by 177 publications

(100 citation statements)

References 29 publications

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“…Each row represented a sample (clustered by age and diet), and each column represented a metabolite (clustered by statistical significance). We then carried out metabolite-set enrichment analysis (MSEA, (Xia and Wishart, 2010)) using the Enrichment Analysis package in MBROLE 2.0 (López-Ibáñez et al, 2016), comparing Human Metabolite Data Base (HMDB) lists for significant age or diet effects using the Benjamini-Hochberg method (Benjamini et al., 2001). Unless otherwise stated, significance for individual metabolites with p values ≤ 0.05 was determined with an FDR α = 0.1.…”

Section: Star⋆methodsmentioning

confidence: 99%

Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans

et al. 2018

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SUMMARY A hallmark of aging is a decline in metabolic homeostasis, which is attenuated by dietary restriction (DR). However, the interaction of aging and DR with the metabolome is not well understood. We report that DR is a stronger modulator of the rat metabolome than age in plasma and tissues. A comparative metabolomic screen in rodents and humans identified circulating sarcosine as being similarly reduced with aging and increased by DR, while sarcosine is also elevated in long-lived Ames dwarf mice. Pathway analysis in aged sarcosine-replete rats identify this biogenic amine as an integral node in the metabolome network. Finally, we show that sarcosine can activate autophagy in cultured cells and enhances autophagic flux in vivo, suggesting a potential role in autophagy induction by DR. Thus, these data identify circulating sarcosine as a biomarker of aging and DR in mammalians and may contribute to age-related alterations in the metabolome and in proteostasis.

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Section: Star⋆methodsmentioning

confidence: 99%

Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans

et al. 2018

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“…Likewise, Z-scores for metabolite levels were computed for naïve D27F mutant, with respect to wild type. The metabolites with the highest absolute Z-scores (>1.96) were selected for an enrichment test using MBRole online software (Lopez-Ibanez et al, 2016) to identify pathways in which altered metabolites are overrepresented. The analysis revealed that the metabolism of purines, pyrimidines, beta-alanine, histidine and sulfur were the most significantly changed in naïve D27F mutant comparatively to wild type (Supplementary Figure S4).…”

Section: D27 Mutation Causes Major Metabolic and Proteomic Changesmentioning

confidence: 99%

Evolutionary dynamics determines adaptation to inactivation of an essential gene

Rodrigues

Shakhnovich

2019

Preprint

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Genetic inactivation of essential genes creates an evolutionary scenario distinct from escape from drug inhibition, but the mechanisms of microbe adaptations in such cases remain unknown. Here we inactivate E. coli dihydrofolate reductase (DHFR) by introducing D27G,N,F chromosomal mutations in a key catalytic residue with subsequent adaptation by serial dilutions. The partial reversal G27->C occurred in three evolutionary trajectories. Conversely, in one trajectory for D27G and in all trajectories for D27F,N strains adapted to grow at very low supplement folAmix concentrations but did not escape entirely from supplement auxotrophy. Major global shifts in metabolome and proteome occurred upon DHFR inactivation, which were partially reversed in adapted strains. Loss of function mutations in two genes, thyA and deoB, ensured adaptation to low folAmix by rerouting the 2-Deoxy-D-ribose-phosphate metabolism from glycolysis towards synthesis of dTMP. Multiple evolutionary pathways of adaptation to low folAmix converge to highly accessible yet suboptimal fitness peak.

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“…4). Each group was then subject to metabolite set enrichment analysis (MSEA) via MBROLE2 [López-Ibáñez et al ., 2016, #73627], with results available in Supplemental Data Set 6.…”

Section: Resultsmentioning

confidence: 99%

Integrative Multi-Omics Analysis of Barley Genotypes Shows Differential Salt-Induced Osmotic Barriers and Response Phases Among Rootzones

Hill

Doblin

et al. 2019

Preprint

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38The mechanisms underlying rootzone-localised responses to salinity stress during early stage 39 of barley development remains fragmentary and elusive. Here, we performed a 40 comprehensive detection of the multi-root-omes (transcriptomes, metabolomes, lipidomes) of 41 a domesticated barley cultivar (Clipper) and a landrace (Sahara) with seedling root growth 42 maintained and restricted in response to salt stress, respectively. Novel generalized linear 43 models were designed to determine differentially expressed genes (DEG) or abundant 44 metabolites (DAM) specific to salt treatments, genotypes, or rootzones (meristematic Z1, 45 elongation Z2, maturation Z3). Based on pathway over-representation of the DEG and DAM, 46 phenylpropanoid biosynthesis is the most statistically over-represented biological pathways 47 among all salinity responses observed. Together with the histological evidence, an intense 48 salt-induced lignin impregnation was found only at the stelic cell wall of Clipper Z2, 49 comparing to a unique elevation of suberin deposition across Sahara Z2. This suggests two 50 differential salt-induced modulations of apoplastic flow between the genotypes. Based on 51 global correlation network construction of the DEG and DAM, callose deposition that 52 potentially adjusted the symplastic flow in roots was almost independent of salinity in 53 rootzones of Clipper, but was markedly decreased in that of Sahara. Through closer 54 examinations of molecular and hormonal clues, we further demonstrate that the salinity 55 response in rootzones of Clipper were mostly at recovery phase, comparing to Sahara with 56 rootzones retained at quiescence. Taken together, we propose that two distinctive salt 57 tolerance mechanisms could exist in Clipper (growth-sustaining) and Sahara (salt-shielding), 58 providing important clues for improving crop plasticity to cope with the deteriorating global 59 salinization of soil.60 61 4 109 to salinity stress differentially, suggesting the distinctive dynamics underpinning the 110 plasticity of different barley genotypes in response to salt stress. 111 6 RESULTS 112 113

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MBROLE 2.0—functional enrichment of chemical compounds

Cited by 177 publications

References 29 publications

Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans

Sarcosine Is Uniquely Modulated by Aging and Dietary Restriction in Rodents and Humans

Evolutionary dynamics determines adaptation to inactivation of an essential gene

Integrative Multi-Omics Analysis of Barley Genotypes Shows Differential Salt-Induced Osmotic Barriers and Response Phases Among Rootzones

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