scholarly journals IsoSolve: an integrative framework to improve isotopic coverage and consolidate isotopic measurements by MS and/or NMR

2021 ◽  
Author(s):  
Pierre Millard ◽  
Sergueï Sokol ◽  
Michael Kohlstedt ◽  
Christoph Wittmann ◽  
Fabien Létisse ◽  
...  
Keyword(s):  
Metabolic Networks ◽  
Isotope Labeling ◽  
Test Case ◽  
Integrative Framework ◽  
Link Type ◽  
Isotopic Analyses ◽  
Label Incorporation ◽  
Nmr Methods ◽  
Isotopic Measurements ◽  
Isotopic Space

ABSTRACTStable-isotope labeling experiments are widely used to investigate the topology and functioning of metabolic networks. Label incorporation into metabolites can be quantified using a broad range of mass spectrometry (MS)and nuclear magnetic resonance (NMR)spectroscopy methods, but in general, no single approach can completely cover isotopic space, even for small metabolites. The number of quantifiable isotopic species could be increased, and the coverage of isotopic space improved, by integrating measurements obtained by different methods; however, this approach has remained largely unexplored because no framework able to deal with partial, heterogeneous isotopic measurements has yet been developed. Here, we present a generic computational framework based on symbolic calculus that can integrate any isotopic dataset by connecting measurements to the chemical structure of the molecules. As a test case, we apply this framework to isotopic analyses of amino acids, which are ubiquitous to life, central to many biological questions, and can be analyzed by a broad range of MS and NMR methods. We demonstrate how this integrative framework helps to i) clarify and improve the coverage of isotopic space, ii) evaluate the complementarity and redundancy of different techniques, iii) consolidate isotopic datasets, iv) design experiments, and v) guide future analytical developments. This framework, which can be applied to any labeled element, isotopic tracer, metabolite, and analytical platform, has been implemented in IsoSolve (available at https://github.com/MetaSysLISBP/IsoSolve and https://pypi.org/project/IsoSolve), an open source software that can be readily integrated into data analysis pipelines.

Methodology for the Validation of Isotopic Analyses by Mass Spectrometry in Stable-Isotope Labeling Experiments

2018 ◽  
Vol 90 (3) ◽  
pp. 1852-1860 ◽  
Author(s):  
Maud Heuillet ◽  
Floriant Bellvert ◽  
Edern Cahoreau ◽  
Fabien Letisse ◽  
Pierre Millard ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Stable Isotope ◽  
Isotope Labeling ◽  
Stable Isotope Labeling ◽  
Isotopic Analyses ◽  
Isotope Labeling Experiments

scholarly journals The nature and origins of decametre-scale porosity in Ordovician carbonate rocks, Halahatang oilfield, Tarim Basin, China

2020 ◽  
Vol 177 (5) ◽  
pp. 1074-1091
Author(s):  
Estibalitz Ukar ◽  
Vinyet Baqués ◽  
Stephen E. Laubach ◽  
Randall Marrett
Keyword(s):  
Tarim Basin ◽  
Velocity Gradient ◽  
Fractured Reservoirs ◽  
Gradient Tensor ◽  
Fault Rocks ◽  
Content Type ◽  
Velocity Gradient Tensor ◽  
Link Type ◽  
Isotopic Analyses ◽  
Supplementary Material

At >7 km depths in the Tarim Basin, hydrocarbon reservoirs in Ordovician rocks of the Yijianfang Formation contain large cavities (c. 10 m or more), vugs, fractures and porous fault rocks. Although some Yijianfang Formation outcrops contain shallow (formed near surface) palaeokarst features, cores from the Halahatang oilfield lack penetrative palaeokarst evidence. Outcrop palaeokarst cavities and opening-mode fractures are mostly mineral filled but some show evidence of secondary dissolution and fault rocks are locally highly (c. 30%) porous. Cores contain textural evidence of repeated formation of dissolution cavities and subsequent filling by cement. Calcite isotopic analyses indicate depths between c. 220 and 2000 m. Correlation of core and image logs shows abundant cement-filled vugs associated with decametre-scale fractured zones with open cavities that host hydrocarbons. A Sm–Nd isochron age of 400 ± 37 Ma for fracture-filling fluorite indicates that cavities in core formed and were partially cemented prior to the Carboniferous, predating Permian oil emplacement. Repeated creation and filling of vugs, timing constraints and the association of vugs with large cavities suggest dissolution related to fractures and faults. In the current high-strain-rate regime, corroborated by velocity gradient tensor analysis of global positioning system (GPS) data, rapid horizontal extension could promote connection of porous and/or solution-enlarged fault rock, fractures and cavities.Supplementary material: Stable isotopic analyses and the velocity gradient tensor and principal direction and magnitude calculation are available at https://doi.org/10.6084/m9.figshare.c.4946046Thematic collection: This article is part of the The Geology of Fractured Reservoirs collection available at: https://www.lyellcollection.org/cc/the-geology-of-fractured-reservoirs

scholarly journals Stable isotope-labeling studies in metabolomics: new insights into structure and dynamics of metabolic networks

Bioanalysis ◽  
2014 ◽  
Vol 6 (4) ◽  
pp. 511-524 ◽  
Author(s):  
Achuthanunni Chokkathukalam ◽  
Dong-Hyun Kim ◽  
Michael P Barrett ◽  
Rainer Breitling ◽  
Darren J Creek
Keyword(s):  
Stable Isotope ◽  
Metabolic Networks ◽  
Isotope Labeling ◽  
Stable Isotope Labeling ◽  
Structure And Dynamics

scholarly journals Need for Laboratory Ecosystems To Unravel the Structures and Functions of Soil Microbial Communities Mediated by Chemistry

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Kateryna Zhalnina ◽  
Karsten Zengler ◽  
Dianne Newman ◽  
Trent R. Northen
Keyword(s):  
Microbial Communities ◽  
Metabolic Networks ◽  
Soil Microbial Communities ◽  
Microbial Interactions ◽  
Microbial Consortia ◽  
Cellular Biology ◽  
Model Organisms ◽  
Soil Microbial ◽  
Integrative Framework ◽  
Genome Annotations

ABSTRACTThe chemistry underpinning microbial interactions provides an integrative framework for linking the activities of individual microbes, microbial communities, plants, and their environments. Currently, we know very little about the functions of genes and metabolites within these communities because genome annotations and functions are derived from the minority of microbes that have been propagated in the laboratory. Yet the diversity, complexity, inaccessibility, and irreproducibility of native microbial consortia limit our ability to interpret chemical signaling and map metabolic networks. In this perspective, we contend that standardized laboratory ecosystems are needed to dissect the chemistry of soil microbiomes. We argue that dissemination and application of standardized laboratory ecosystems will be transformative for the field, much like how model organisms have played critical roles in advancing biochemistry and molecular and cellular biology. Community consensus on fabricated ecosystems (“EcoFABs”) along with protocols and data standards will integrate efforts and enable rapid improvements in our understanding of the biochemical ecology of microbial communities.

scholarly journals An Integrative Framework to Test Purity Motivations in Environmental Behavior

2018 ◽  
Author(s):  
Sonya Sachdeva ◽  
Reihane Boghrati ◽  
Morteza Dehghani
Keyword(s):  
Social Media ◽  
Computational Linguistics ◽  
Environmental Behavior ◽  
Environmental Issues ◽  
Environmental Context ◽  
Integrative Approach ◽  
Test Case ◽  
Behavioral Experiments ◽  
Environmental Cleanup ◽  
Integrative Framework

Environmental issues are often discussed in purity-related terms. For instance, pollution, contamination, toxicity, and degradation are all concepts that can evoke notions of (im)purity in an environmental context. In this paper, we assess the efficacy of purity-based norms as drivers of environmental behavior. First, using a social media-based environmental cleanup campaign as a test case, we find that purity based norms, increase participation in the campaign. We then replicate and extend these findings in three behavioral experiments, finding that the effects of purity on environmental behavior are strongest for people who are more deeply connected with an in-group. Using an integrative approach to combine computational linguistics with behavioral experiments, we find that purity-based norms can be powerful motivators of environmental behavior, particularly if they emphasize the relation to group identity.

scholarly journals Medusa: software to build and analyze ensembles of genome-scale metabolic network reconstructions

2019 ◽  
Author(s):  
Gregory L. Medlock ◽  
Jason A. Papin
Keyword(s):  
Machine Learning ◽  
Experimental Data ◽  
Computational Biology ◽  
Metabolic Network ◽  
Metabolic Networks ◽  
Ensemble Simulations ◽  
Link Type ◽  
Genome Scale ◽  
Python Package

AbstractUncertainty in the structure and parameters of networks is ubiquitous across computational biology. In constraint-based reconstruction and analysis of metabolic networks, this uncertainty is present both during the reconstruction of networks and in simulations performed with them. Here, we present Medusa, a Python package for the generation and analysis of ensembles of genome-scale metabolic network reconstructions. Medusa builds on the COBRApy package for constraint-based reconstruction and analysis by compressing a set of models into a compact ensemble object, providing functions for the generation of ensembles using experimental data, and extending constraint-based analyses to ensemble scale. We demonstrate how Medusa can be used to generate ensembles, perform ensemble simulations, and how machine learning can be used in conjunction with Medusa to guide the curation of genome-scale metabolic network reconstructions. Medusa is available under the permissive MIT license from the Python Packaging Index (https://pypi.org/) and from github (https://github.com/gregmedlock/Medusa/), and comprehensive documentation is available at https://medusa.readthedocs.io/en/latest/.

scholarly journals NMR Methods for Quantitative Isotopomer Rates in Real-Time Metabolism of Cells

2019 ◽  
Author(s):  
Michelle AC Reed ◽  
Jennie Roberts ◽  
Peter Gierth ◽  
Ēriks Kupče ◽  
Ulrich L Günther
Keyword(s):  
Real Time ◽  
Metabolic Flux ◽  
Coupling Constants ◽  
Special Focus ◽  
Flux Analysis ◽  
Coupling Constant ◽  
Difference Spectra ◽  
Precise Knowledge ◽  
Label Incorporation ◽  
Nmr Methods

AbstractTracer-based metabolism is becoming increasingly important to study metabolic mechanisms in cells. NMR offers several approaches to measure label incorporation in metabolites, including 13C and 1H-detected spectra. The latter are generally more sensitive but quantification depends on the proton carbon 1JCH coupling constant which varies significantly between different metabolites. It is therefore not possible to have one experiment optimised for all metabolites and quantification of 1H-edited spectra such as HSQCs requires precise knowledge of coupling constants. Increasing interest in tracer-based and metabolic flux analysis requires robust analyses with reasonably small acquisition times. Here we compare 13C-filtered and 13C-edited methods for quantification with a special focus towards application in real-time NMR of cancer cells under near-physiological conditions. We find an approach using a double-filter most suitable and sufficiently robust to reliably obtain 13C-incorporations from difference spectra. This is demonstrated for JJN3 multiple myeloma cells processing glucose over 24h.

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