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  1. Article ; Online: Metabolic Pathway Analysis: Advantages and Pitfalls for the Functional Interpretation of Metabolomics and Lipidomics Data.

    Tsouka, Sofia / Masoodi, Mojgan

    Biomolecules

    2023  Volume 13, Issue 2

    Abstract: Over the past decades, pathway analysis has become one of the most commonly used approaches for the functional interpretation of metabolomics data. Although the approach is widely used, it is not well standardized and the impact of different ... ...

    Abstract Over the past decades, pathway analysis has become one of the most commonly used approaches for the functional interpretation of metabolomics data. Although the approach is widely used, it is not well standardized and the impact of different methodologies on the functional outcome is not well understood. Using four publicly available datasets, we investigated two main aspects of topological pathway analysis, namely the consideration of non-human native enzymatic reactions (e.g., from microbiota) and the interconnectivity of individual pathways. The exclusion of non-human native reactions led to detached and poorly represented reaction networks and to loss of information. The consideration of connectivity between pathways led to better emphasis of certain central metabolites in the network; however, it occasionally overemphasized the hub compounds. We proposed and examined a penalization scheme to diminish the effect of such compounds in the pathway evaluation. In order to compare and assess the results between different methodologies, we also performed over-representation analysis of the same datasets. We believe that our findings will raise awareness on both the capabilities and shortcomings of the currently used pathway analysis practices in metabolomics. Additionally, it will provide insights on various methodologies and strategies that should be considered for the analysis and interpretation of metabolomics data.
    MeSH term(s) Lipidomics ; Metabolomics/methods ; Metabolic Networks and Pathways
    Language English
    Publishing date 2023-01-27
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom13020244
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Transcriptomics-driven metabolic pathway analysis reveals similar alterations in lipid metabolism in mouse MASH model and human.

    Tsouka, Sofia / Kumar, Pavitra / Seubnooch, Patcharamon / Freiburghaus, Katrin / St-Pierre, Marie / Dufour, Jean-François / Masoodi, Mojgan

    Communications medicine

    2024  Volume 4, Issue 1, Page(s) 39

    Abstract: Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease worldwide, and can rapidly progress to metabolic dysfunction-associated steatohepatitis (MASH). Accurate preclinical models and ... ...

    Abstract Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease worldwide, and can rapidly progress to metabolic dysfunction-associated steatohepatitis (MASH). Accurate preclinical models and methodologies are needed to understand underlying metabolic mechanisms and develop treatment strategies. Through meta-analysis of currently proposed mouse models, we hypothesized that a diet- and chemical-induced MASH model closely resembles the observed lipid metabolism alterations in humans.
    Methods: We developed transcriptomics-driven metabolic pathway analysis (TDMPA), a method to aid in the evaluation of metabolic resemblance. TDMPA uses genome-scale metabolic models to calculate enzymatic reaction perturbations from gene expression data. We performed TDMPA to score and compare metabolic pathway alterations in MASH mouse models to human MASH signatures. We used an already-established WD+CCl4-induced MASH model and performed functional assays and lipidomics to confirm TDMPA findings.
    Results: Both human MASH and mouse models exhibit numerous altered metabolic pathways, including triglyceride biosynthesis, fatty acid beta-oxidation, bile acid biosynthesis, cholesterol metabolism, and oxidative phosphorylation. We confirm a significant reduction in mitochondrial functions and bioenergetics, as well as in acylcarnitines for the mouse model. We identify a wide range of lipid species within the most perturbed pathways predicted by TDMPA. Triglycerides, phospholipids, and bile acids are increased significantly in mouse MASH liver, confirming our initial observations.
    Conclusions: We introduce TDMPA, a methodology for evaluating metabolic pathway alterations in metabolic disorders. By comparing metabolic signatures that typify human MASH, we show a good metabolic resemblance of the WD+CCl4 mouse model. Our presented approach provides a valuable tool for defining metabolic space to aid experimental design for assessing metabolism.
    Language English
    Publishing date 2024-03-05
    Publishing country England
    Document type Journal Article
    ISSN 2730-664X
    ISSN (online) 2730-664X
    DOI 10.1038/s43856-024-00465-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Lipid Mediators in Critically Ill Patients: A Step Towards Precision Medicine.

    Cioccari, Luca / Luethi, Nora / Masoodi, Mojgan

    Frontiers in immunology

    2020  Volume 11, Page(s) 599853

    Abstract: A dysregulated response to systemic inflammation is a common pathophysiological feature of most conditions encountered in the intensive care unit (ICU). Recent evidence indicates that a dysregulated inflammatory response is involved in the pathogenesis ... ...

    Abstract A dysregulated response to systemic inflammation is a common pathophysiological feature of most conditions encountered in the intensive care unit (ICU). Recent evidence indicates that a dysregulated inflammatory response is involved in the pathogenesis of various ICU-related disorders associated with high mortality, including sepsis, acute respiratory distress syndrome, cerebral and myocardial ischemia, and acute kidney injury. Moreover, persistent or non-resolving inflammation may lead to the syndrome of persistent critical illness, characterized by acquired immunosuppression, catabolism and poor long-term functional outcomes. Despite decades of research, management of many disorders in the ICU is mostly supportive, and current therapeutic strategies often do not take into account the heterogeneity of the patient population, underlying chronic conditions, nor the individual state of the immune response. Fatty acid-derived lipid mediators are recognized as key players in the generation and resolution of inflammation, and their signature provides specific information on patients' inflammatory status and immune response. Lipidomics is increasingly recognized as a powerful tool to assess lipid metabolism and the interaction between metabolic changes and the immune system
    MeSH term(s) Acute Kidney Injury/immunology ; Acute Kidney Injury/therapy ; Brain Ischemia/immunology ; Brain Ischemia/therapy ; Critical Illness ; Humans ; Lipids/immunology ; Myocardial Ischemia/immunology ; Myocardial Ischemia/therapy ; Precision Medicine ; Respiratory Distress Syndrome/immunology ; Respiratory Distress Syndrome/therapy ; Sepsis/immunology ; Sepsis/therapy
    Chemical Substances Lipids
    Language English
    Publishing date 2020-11-25
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.599853
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Untargeted Profiling of Bile Acids and Lysophospholipids Identifies the Lipid Signature Associated with Glycemic Outcome in an Obese Non-Diabetic Clinical Cohort.

    Christinat, Nicolas / Valsesia, Armand / Masoodi, Mojgan

    Biomolecules

    2020  Volume 10, Issue 7

    Abstract: The development of high throughput assays for assessing lipid metabolism in metabolic disorders, especially in diabetes research, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH), provides a reliable tool for identifying ... ...

    Abstract The development of high throughput assays for assessing lipid metabolism in metabolic disorders, especially in diabetes research, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH), provides a reliable tool for identifying and characterizing potential biomarkers in human plasma for early diagnosis or prognosis of the disease and/or responses to a specific treatment. Predicting the outcome of weight loss or weight management programs is a challenging yet important aspect of such a program's success. The characterization of potential biomarkers of metabolic disorders, such as lysophospholipids and bile acids, in large human clinical cohorts could provide a useful tool for successful predictions. In this study, we validated an LC-MS method combining the targeted and untargeted detection of these lipid species. Its potential for biomarker discovery was demonstrated in a well-characterized overweight/obese cohort subjected to a low-caloric diet intervention, followed by a weight maintenance phase. Relevant markers predicting successful responses to the low-caloric diet intervention for both weight loss and glycemic control improvements were identified. The response to a controlled weight loss intervention could be best predicted using the baseline concentration of three lysophospholipids (PC(22:4/0:0), PE(17:1/0:0), and PC(22:5/0:0)). Insulin resistance on the other hand could be best predicted using clinical parameters and levels of circulating lysophospholipids and bile acids. Our approach provides a robust tool not only for research purposes, but also for clinical practice, as well as designing new clinical interventions or assessing responses to specific treatment. Considering this, it presents a step toward personalized medicine.
    MeSH term(s) Adult ; Bile Acids and Salts/blood ; Biomarkers/blood ; Body Weight Maintenance ; Caloric Restriction/methods ; Chromatography, Liquid ; Cohort Studies ; Female ; Humans ; Insulin Resistance ; Lipid Metabolism ; Lysophospholipids/blood ; Male ; Mass Spectrometry ; Metabolomics ; Middle Aged ; Obesity/diet therapy ; Obesity/metabolism ; Treatment Outcome
    Chemical Substances Bile Acids and Salts ; Biomarkers ; Lysophospholipids
    Language English
    Publishing date 2020-07-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom10071049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Characterisation of hepatic lipid signature distributed across the liver zonation using mass spectrometry imaging.

    Seubnooch, Patcharamon / Montani, Matteo / Tsouka, Sofia / Claude, Emmanuelle / Rafiqi, Umara / Perren, Aurel / Dufour, Jean-Francois / Masoodi, Mojgan

    JHEP reports : innovation in hepatology

    2023  Volume 5, Issue 6, Page(s) 100725

    Abstract: Background & aims: Lipid metabolism plays an important role in liver pathophysiology. The liver lobule asymmetrically distributes oxygen and nutrition, resulting in heterogeneous metabolic functions. Periportal and pericentral hepatocytes have different ...

    Abstract Background & aims: Lipid metabolism plays an important role in liver pathophysiology. The liver lobule asymmetrically distributes oxygen and nutrition, resulting in heterogeneous metabolic functions. Periportal and pericentral hepatocytes have different metabolic functions, which lead to generating liver zonation. We developed spatial metabolic imaging using desorption electrospray ionisation mass spectrometry to investigate lipid distribution across liver zonation with high reproducibility and accuracy.
    Methods: Fresh frozen livers from healthy mice with control diet were analysed using desorption electrospray ionisation mass spectrometry imaging. Imaging was performed at 50 μm × 50 μm pixel size. Regions of interest (ROIs) were manually created by co-registering with histological data to determine the spatial hepatic lipids across liver zonation. The ROIs were confirmed by double immunofluorescence. The mass list of specific ROIs was automatically created, and univariate and multivariate statistical analysis were performed to identify statistically significant lipids across liver zonation.
    Results: A wide range of lipid species was identified, including fatty acids, phospholipids, triacylglycerols, diacylglycerols, ceramides, and sphingolipids. We characterised hepatic lipid signatures in three different liver zones (periportal zone, midzone, and pericentral zone) and validated the reproducibility of our method for measuring a wide range of lipids. Fatty acids were predominantly detected in the periportal region, whereas phospholipids were distributed in both the periportal and pericentral zones. Interestingly, phosphatidylinositols, PI(36:2), PI(36:3), PI(36:4), PI(38:5), and PI(40:6) were located predominantly in the midzone (zone 2). Triacylglycerols and diacylglycerols were detected mainly in the pericentral region.
    Conclusions: The ability to accurately assess zone-specific hepatic lipid distribution in the liver could lead to a better understanding of lipid metabolism during the progression of liver disease.
    Impact and implications: Zone-specific hepatic lipid metabolism could play an important role in lipid homoeostasis during disease progression. Herein, we defined the zone-specific references of hepatic lipid species in the three liver zones using molecular imaging. The
    Language English
    Publishing date 2023-03-09
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2589-5559
    ISSN (online) 2589-5559
    DOI 10.1016/j.jhepr.2023.100725
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Comprehensive Lipoprotein Characterization Using Lipidomics Analysis of Human Plasma.

    Christinat, Nicolas / Masoodi, Mojgan

    Journal of proteome research

    2017  Volume 16, Issue 8, Page(s) 2947–2953

    Abstract: Lipoproteins are responsible for the transport of lipids and other nutrients in the circulation and therefore play an important role in lipid metabolism and dyslipidemia. They have also been linked to multiple metabolic disorders including cardiovascular ...

    Abstract Lipoproteins are responsible for the transport of lipids and other nutrients in the circulation and therefore play an important role in lipid metabolism and dyslipidemia. They have also been linked to multiple metabolic disorders including cardiovascular disease, and thus understanding their lipid composition is of crucial importance. Characterization of lipoproteins is a challenging task due to their heterogeneity. In particular, their fractionation is often laborious and time-consuming, making large sets of clinical samples difficult to analyze. We developed and validated lipidomics analysis of lipoproteins including chylomicrons, very low-density, low-density, and high-density lipoproteins. Lipoproteins were first fractionated by polyacrylamide tube gel electrophoresis, and, after liquid-liquid extraction, lipids were analyzed by direct-infusion mass spectrometry. About 100 unique lipid species were detected with good reproducibility and reliability. In addition to their lipid composition, valuable information on the fatty acid composition of lipoproteins and lipids was obtained. The presented method offers in-depth analysis of the lipid as well as fatty acid composition of lipoproteins while allowing a good sample throughput. It is thus especially suited for studying lipid associated diseases in clinical cohorts.
    MeSH term(s) Blood Protein Electrophoresis ; Humans ; Lipids/blood ; Lipoproteins/analysis ; Lipoproteins, HDL/blood ; Lipoproteins, LDL/blood ; Lipoproteins, VLDL/blood ; Liquid-Liquid Extraction ; Mass Spectrometry ; Methods
    Chemical Substances Lipids ; Lipoproteins ; Lipoproteins, HDL ; Lipoproteins, LDL ; Lipoproteins, VLDL
    Language English
    Publishing date 2017-07-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.7b00236
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: An integrative multi-omics approach reveals new central nervous system pathway alterations in Alzheimer's disease.

    Clark, Christopher / Dayon, Loïc / Masoodi, Mojgan / Bowman, Gene L / Popp, Julius

    Alzheimer's research & therapy

    2021  Volume 13, Issue 1, Page(s) 71

    Abstract: Background: Multiple pathophysiological processes have been described in Alzheimer's disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We ... ...

    Abstract Background: Multiple pathophysiological processes have been described in Alzheimer's disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We hypothesize that specific molecular patterns indicating both known and yet unidentified pathway alterations are associated with distinct aspects of AD pathology.
    Methods: We performed multi-level cerebrospinal fluid (CSF) omics in a well-characterized cohort of older adults with normal cognition, mild cognitive impairment, and mild dementia. Proteomics, metabolomics, lipidomics, one-carbon metabolism, and neuroinflammation related molecules were analyzed at single-omic level with correlation and regression approaches. Multi-omics factor analysis was used to integrate all biological levels. Identified analytes were used to construct best predictive models of the presence of AD pathology and of cognitive decline with multifactorial regression analysis. Pathway enrichment analysis identified pathway alterations in AD.
    Results: Multi-omics integration identified five major dimensions of heterogeneity explaining the variance within the cohort and differentially associated with AD. Further analysis exposed multiple interactions between single 'omics modalities and distinct multi-omics molecular signatures differentially related to amyloid pathology, neuronal injury, and tau hyperphosphorylation. Enrichment pathway analysis revealed overrepresentation of the hemostasis, immune response, and extracellular matrix signaling pathways in association with AD. Finally, combinations of four molecules improved prediction of both AD (protein 14-3-3 zeta/delta, clusterin, interleukin-15, and transgelin-2) and cognitive decline (protein 14-3-3 zeta/delta, clusterin, cholesteryl ester 27:1 16:0 and monocyte chemoattractant protein-1).
    Conclusions: Applying an integrative multi-omics approach we report novel molecular and pathways alterations associated with AD pathology. These findings are relevant for the development of personalized diagnosis and treatment approaches in AD.
    MeSH term(s) Aged ; Alzheimer Disease/genetics ; Amyloid beta-Peptides ; Biomarkers ; Central Nervous System ; Humans ; Peptide Fragments ; tau Proteins
    Chemical Substances Amyloid beta-Peptides ; Biomarkers ; Peptide Fragments ; tau Proteins
    Language English
    Publishing date 2021-04-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2506521-X
    ISSN 1758-9193 ; 1758-9193
    ISSN (online) 1758-9193
    ISSN 1758-9193
    DOI 10.1186/s13195-021-00814-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Current perspectives on mitochondrial dysfunction in migraine.

    Bohra, Shraman Kumar / Achar, Raghu Ram / Chidambaram, Saravana Babu / Pellegrino, Christophe / Laurin, Jerome / Masoodi, Mojgan / Srinivasan, Asha

    The European journal of neuroscience

    2022  Volume 56, Issue 1, Page(s) 3738–3754

    Abstract: Mitochondria are an autonomous organelle that plays a crucial role in the metabolic aspects of a cell. Cortical spreading depression (CSD) and fluctuations in the cerebral blood flow have for long been mechanisms underlying migraine. It is a ... ...

    Abstract Mitochondria are an autonomous organelle that plays a crucial role in the metabolic aspects of a cell. Cortical spreading depression (CSD) and fluctuations in the cerebral blood flow have for long been mechanisms underlying migraine. It is a neurovascular disorder with a unilateral manifestation of disturbing, throbbing and pulsating head pain. Migraine affects 2.6% and 21.7% of the general population and is the major cause of partial disability in the age group 15-49. Higher mutation rates, imbalance in concentration of physiologically relevant molecules and oxidative stress biomarkers have been the main themes of discussion in determining the role of mitochondrial disability in migraine. The correlation of migraine with other disorders like hemiplegic migraine; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS]; tension-type headache (TTH); cyclic vomiting syndrome (CVS), ischaemic stroke; and hypertension has helped in the assessment of the physiological and morphogenetic basis of migraine. Here, we have reviewed the different nuances of mitochondrial dysfunction and migraine. The different mtDNA polymorphisms that can affect the generation and transmission of nerve impulse has been highlighted and supported with research findings. In addition to this, the genetic basis of migraine pathogenesis as a consequence of mutations in nuclear DNA that can, in turn, affect the synthesis of defective mitochondrial proteins is discussed along with a brief overview of epigenetic profile. This review gives an overview of the pathophysiology of migraine and explores mitochondrial dysfunction as a potential underlying mechanism. Also, therapeutic supplements for managing migraine have been discussed at different junctures in this paper.
    MeSH term(s) Brain Ischemia ; Humans ; MELAS Syndrome/drug therapy ; MELAS Syndrome/genetics ; MELAS Syndrome/pathology ; Migraine Disorders/genetics ; Mitochondria/genetics ; Mutation ; Stroke/complications
    Language English
    Publishing date 2022-05-12
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.15676
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  9. Article: Exploring Valine Metabolism in Astrocytic and Liver Cells: Lesson from Clinical Observation in TBI Patients for Nutritional Intervention.

    Sonnay, Sarah / Christinat, Nicolas / Thevenet, Jonathan / Wiederkehr, Andreas / Chakrabarti, Anirikh / Masoodi, Mojgan

    Biomedicines

    2020  Volume 8, Issue 11

    Abstract: The utilization of alternative energy substrates to glucose could be beneficial in traumatic brain injury (TBI). Recent clinical data obtained in TBI patients reported valine, β-hydroxyisobutyrate (ibHB) and 2-ketoisovaleric acid (2-KIV) as three of the ... ...

    Abstract The utilization of alternative energy substrates to glucose could be beneficial in traumatic brain injury (TBI). Recent clinical data obtained in TBI patients reported valine, β-hydroxyisobutyrate (ibHB) and 2-ketoisovaleric acid (2-KIV) as three of the main predictors of TBI outcome. In particular, higher levels of ibHB, 2-KIV, and valine in cerebral microdialysis (CMD) were associated with better clinical outcome. In this study, we investigate the correlations between circulating and CMD levels of these metabolites. We hypothesized that the liver can metabolize valine and provide a significant amount of intermediate metabolites, which can be further metabolized in the brain. We aimed to assess the metabolism of valine in human-induced pluripotent stem cell (iPSC)-derived astrocytes and HepG2 cells using
    Language English
    Publishing date 2020-11-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines8110487
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  10. Article ; Online: High-Throughput Quantitative Lipidomics Analysis of Nonesterified Fatty Acids in Plasma by LC-MS.

    Christinat, Nicolas / Morin-Rivron, Delphine / Masoodi, Mojgan

    Methods in molecular biology (Clifton, N.J.)

    2017  Volume 1619, Page(s) 183–191

    Abstract: Nonesterified fatty acids are important biological molecules which have multiple functions such as energy storage, gene regulation, or cell signaling. Comprehensive profiling of nonesterified fatty acids in biofluids can facilitate studying and ... ...

    Abstract Nonesterified fatty acids are important biological molecules which have multiple functions such as energy storage, gene regulation, or cell signaling. Comprehensive profiling of nonesterified fatty acids in biofluids can facilitate studying and understanding their roles in biological systems. For these reasons, we have developed and validated a high-throughput, nontargeted lipidomics method coupling liquid chromatography to high-resolution mass spectrometry for quantitative analysis of nonesterified fatty acids. Sufficient chromatographic separation is achieved to separate positional isomers such as polyunsaturated and branched-chain species and quantify a wide range of nonesterified fatty acids in human plasma samples. However, this method is not limited only to these fatty acid species and offers the possibility to perform untargeted screening of additional nonesterified fatty acid species.
    MeSH term(s) Chromatography, Liquid ; Fatty Acids/blood ; Fatty Acids, Nonesterified/blood ; High-Throughput Screening Assays ; Humans ; Lipids/blood ; Metabolome ; Metabolomics/methods ; Software ; Statistics as Topic ; Tandem Mass Spectrometry
    Chemical Substances Fatty Acids ; Fatty Acids, Nonesterified ; Lipids
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-7057-5_14
    Database MEDical Literature Analysis and Retrieval System OnLINE

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