| 1. |
- Balgoma, David, et al.
(author)
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Orthogonality in Principal Component Analysis Allows the Discovery of Lipids in the Jejunum That Are Independent of Ad Libitum Feeding
- 2022
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In: Metabolites. - : MDPI. - 2218-1989 .- 2218-1989. ; 12:9
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Journal article (peer-reviewed)abstract
- Ad libitum feeding of experimental animals is preferred because of medical relevance together with technical and practical considerations. In addition, ethical committees may require ad libitum feeding. However, feeding affects the metabolism so ad libitum feeding may mask the effects of drugs on tissues directly involved in the digestion process (e.g., jejunum and liver). Despite this effect, principal component analysis has the potential of identifying metabolic traits that are statistically independent (orthogonal) to ad libitum feeding. Consequently, we used principal component analysis to discover the metabolic effects of doxorubicin independent of ad libitum feeding. First, we analyzed the lipidome of the jejunum and the liver of rats treated with vehicle or doxorubicin. Subsequently, we performed principal component analysis. We could identify a principal component associated to the hydrolysis of lipids during digestion and a group of lipids that were orthogonal. These lipids in the jejunum increased with the treatment time and presented a polyunsaturated fatty acid as common structural trait. This characteristic suggests that doxorubicin increases polyunsaturated fatty acids. This behavior agrees with our previous in vitro results and suggests that doxorubicin sensitized the jejunum to ferroptosis, which may partially explain the toxicity of doxorubicin in the intestines.
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| 2. |
- Balgoma, David, et al.
(author)
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Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver
- 2020
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In: Metabolomics. - : SPRINGER. - 1573-3882 .- 1573-3890. ; 16:1
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Journal article (peer-reviewed)abstract
- Introduction: The abuse of anabolic androgenic steroids (AASs) is a source of public concern because of their adverse effects. Supratherapeutic doses of AASs are known to be hepatotoxic and regulate the lipoproteins in plasma by modifying the metabolism of lipids in the liver, which is associated with metabolic diseases. However, the effect of AASs on the profile of lipids in plasma is unknown.Objectives: To describe the changes in the plasma lipidome exerted by AASs and to discuss these changes in the light of previous research about AASs and de novo lipogenesis in the liver.Methods: We treated male Wistar rats with supratherapeutic doses of nandrolone decanoate and testosterone undecanoate. Subsequently, we isolated the blood plasma and performed lipidomics analysis by liquid chromatography-high resolution mass spectrometry.Results: Lipid profiling revealed a decrease of sphingolipids and glycerolipids with palmitic, palmitoleic, stearic, and oleic acids. In addition, lipid profiling revealed an increase in free fatty acids and glycerophospholipids with odd-numbered chain fatty acids and/or arachidonic acid.Conclusion: The lipid profile presented herein reports the imprint of AASs on the plasma lipidome, which mirrors the downregulation of de novo lipogenesis in the liver. In a broader perspective, this profile will help to understand the influence of androgens on the lipid metabolism in future studies of diseases with dysregulated lipogenesis (e.g. type 2 diabetes, fatty liver disease, and hepatocellular carcinoma).
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| 3. |
- Balgoma, David, et al.
(author)
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Anthracyclins Increase PUFAs : Potential Implications in ER Stress and Cell Death
- 2021
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In: Cells. - : MDPI. - 2073-4409. ; 10:5
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Journal article (peer-reviewed)abstract
- Metabolic and personalized interventions in cancer treatment require a better understanding of the relationship between the induction of cell death and metabolism. Consequently, we treated three primary liver cancer cell lines with two anthracyclins (doxorubicin and idarubin) and studied the changes in the lipidome. We found that both anthracyclins in the three cell lines increased the levels of polyunsaturated fatty acids (PUFAs) and alkylacylglycerophosphoethanolamines (etherPEs) with PUFAs. As PUFAs and alkylacylglycerophospholipids with PUFAs are fundamental in lipid peroxidation during ferroptotic cell death, our results suggest supplementation with PUFAs and/or etherPEs with PUFAs as a potential general adjuvant of anthracyclins. In contrast, neither the markers of de novo lipogenesis nor cholesterol lipids presented the same trend in all cell lines and treatments. In agreement with previous research, this suggests that modulation of the metabolism of cholesterol could be considered a specific adjuvant of anthracyclins depending on the type of tumor and the individual. Finally, in agreement with previous research, we found a relationship across the different cell types between: (i) the change in endoplasmic reticulum (ER) stress, and (ii) the imbalance between PUFAs and cholesterol and saturated lipids. In the light of previous research, this imbalance partially explains the sensitivity to anthracyclins of the different cells. In conclusion, our results suggest that the modulation of different lipid metabolic pathways may be considered for generalized and personalized metabochemotherapies.
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| 4. |
- Balgoma, David, et al.
(author)
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Common Fatty Markers in Diseases with Dysregulated Lipogenesis
- 2019
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In: Trends in endocrinology and metabolism. - : ELSEVIER SCIENCE LONDON. - 1043-2760 .- 1879-3061. ; 30:5, s. 283-285
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Journal article (peer-reviewed)abstract
- Recent studies have reported the upregulation of a subgroup of triacylglycerides as markers of different diseases with dysregulated lipogenesis, which means that these markers are not selective. This observation has a deep impact on their use as diagnostic tools in clinical practice (e.g., markers of risk of type 2 diabetes).
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| 5. |
- Balgoma, David, et al.
(author)
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Etherglycerophospholipids and ferroptosis : structure, regulation, and location
- 2021
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In: Trends in endocrinology and metabolism. - : Elsevier. - 1043-2760 .- 1879-3061. ; 32:12, s. 960-962
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Journal article (other academic/artistic)abstract
- Two pioneering studies by Zou et al. and Cui et al. have reported that the synthesis of etherglycerophospholipids (etherPLs) sensitizes cells to ferroptosis. The location and regulation of etherPLs suggest that: (i) lipid peroxidation in the inner leaflet of the plasma membrane might be of importance in ferroptosis, and (ii) different etherPLs may differently sensitize cells to ferroptosis.
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| 6. |
- Balgoma, David, et al.
(author)
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Lipidomics Issues on Human Positive ssRNA Virus Infection : An Update
- 2020
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In: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 10:9
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Research review (peer-reviewed)abstract
- The pathogenic mechanisms underlying the Biology and Biochemistry of viral infections are known to depend on the lipid metabolism of infected cells. From a lipidomics viewpoint, there are a variety of mechanisms involving virus infection that encompass virus entry, the disturbance of host cell lipid metabolism, and the role played by diverse lipids in regard to the infection effectiveness. All these aspects have currently been tackled separately as independent issues and focused on the function of proteins. Here, we review the role of cholesterol and other lipids in ssRNA+ infection.
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| 7. |
- Balgoma, David, et al.
(author)
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Modeling the fragmentation patterns of triacylglycerides in mass spectrometry allows the quantification of the regioisomers with a minimal number of standards
- 2019
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In: Analytica Chimica Acta. - : Elsevier BV. - 0003-2670 .- 1873-4324. ; 1057, s. 60-69
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Journal article (peer-reviewed)abstract
- Mass spectrometry allows the relative quantification of the regioisomers of triacylglycerides by the calibration of their fragmentation patterns. However, due to the plethora of regioisomers of triacylglycerides, calibration with every standard is not feasible. An analytical challenge in the field is the prediction of the fragmentation patterns of triacylglycerides to quantify their regioisomers. Thus, we aimed to model these fragmentation patterns to quantify the regioisomeric composition, even for those without commercially available standards. In a first step, we modeled the fragmentation patterns of the regioisomers of triacylglycerides obtained from different published datasets. We found the same qualitative trends of fragmentation beyond differences in the type of adduct in these datasets (both [M+NH4]+ and [M+H]+), and the type of instrument (orbitrap, Q-ToF, ion-trap, single quadrupole, and triple quadrupole). However, the quantitative trends of fragmentation were adduct and instrument specific. From these observations, we modeled quantitatively the common trends of fragmentation of triacylglycerides in every dataset. In a second step, we applied this methodology on a Synapt G2S Q-ToF to quantify the regioisomers of triacylglycerides in sunflower and olive oils. The results of our quantification were in good agreement with previous published quantifications of triacylglycerides, even for regioisomers that were not present in the training dataset. The species with more than two highly unsaturated fatty acids (arachidonic, eicosapentaenoic, and docosahexaenoic acids) showed a complex behavior and lower predictability of their fragmentation patterns. However, this framework presents the capacity to model this behavior when more data are available. It would be also applicable to standardize the quantification of the regioisomers of triacylglycerides in an inter-laboratory ring study.
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| 8. |
- Gil-de-Gomez, Luis, et al.
(author)
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Lipidomic-Based Advances in Diagnosis and Modulation of Immune Response to Cancer
- 2020
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In: Metabolites. - : MDPI. - 2218-1989 .- 2218-1989. ; 10:8
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Research review (peer-reviewed)abstract
- While immunotherapies for diverse types of cancer are effective in many cases, relapse is still a lingering problem. Like tumor cells, activated immune cells have an anabolic metabolic profile, relying on glycolysis and the increased uptake and synthesis of fatty acids. In contrast, immature antigen-presenting cells, as well as anergic and exhausted T-cells have a catabolic metabolic profile that uses oxidative phosphorylation to provide energy for cellular processes. One goal for enhancing current immunotherapies is to identify metabolic pathways supporting the immune response to tumor antigens. A robust cell expansion and an active modulation via immune checkpoints and cytokine release are required for effective immunity. Lipids, as one of the main components of the cell membrane, are the key regulators of cell signaling and proliferation. Therefore, lipid metabolism reprogramming may impact proliferation and generate dysfunctional immune cells promoting tumor growth. Based on lipid-driven signatures, the discrimination between responsiveness and tolerance to tumor cells will support the development of accurate biomarkers and the identification of potential therapeutic targets. These findings may improve existing immunotherapies and ultimately prevent immune escape in patients for whom existing treatments have failed.
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| 9. |
- Kolmert, Johan, et al.
(author)
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Urinary Leukotriene E-4 and Prostaglandin D-2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation A Clinical Observational Study
- 2021
-
In: American Journal of Respiratory and Critical Care Medicine. - NEW YORK, USA : AMER THORACIC SOC. - 1073-449X .- 1535-4970. ; 203:1, s. 37-53
-
Journal article (peer-reviewed)abstract
- Rationale: New approaches are needed to guide personalized treatment of asthma. Objectives: To test if urinary eicosanoid metabolites can direct asthma phenotyping. Methods: Urinary metabolites of prostaglandins (PGs), cysteinyl leukotrienes (CysLTs), and isoprostanes were quantified in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy control participants. Validation was performed internally in 302 participants with SA followed up after 12-18 months and externally in 95 adolescents with asthma. Measurement and Main Results: Metabolite concentrations in healthy control participants were unrelated to age, body mass index, and sex, except for the PGE(2) pathway. Eicosanoid concentrations were generally greater in participants with MMA relative to healthy control participants, with further elevations in participants with SA. However, PGE(2) metabolite concentrations were either the same or lower in male nonsmokers with asthma than in healthy control participants. Metabolite concentrations were unchanged in those with asthma who adhered to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas those with SA treated with omalizumab had lower concentrations of LTE4 and the PGD(2) metabolite 2,3-dinor-11 beta-PGF(2 alpha). High concentrations of LTE4 and PGD(2) metabolites were associated with lower lung function and increased amounts of exhaled nitric oxide and eosinophil markers in blood, sputum, and urine in U-BIOARED participants and in adolescents with asthma. These type 2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study and were found to be as sensitive to detect T2 inflammation as the established biomarkers. Conclusions: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new noninvasive approach for molecular phenotyping of adult and adolescent asthma.
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| 10. |
- Kopsida, Maria, et al.
(author)
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Inhibiting the endoplasmic reticulum stress response enhances the effect of doxorubicin by altering the lipid metabolism of liver cancer cells
- 2024
-
In: Molecular Metabolism. - : Elsevier. - 2212-8778. ; 79
-
Journal article (peer-reviewed)abstract
- Hepatocellular carcinoma (HCC) is characterized by a low and variable response to chemotherapeutic treatments. One contributing factor to the overall pharmacodynamics is the activation of endoplasmic reticulum (ER) stress pathways. This is a cellular stress mechanism that becomes activated when the cell's need for protein synthesis surpasses the ER's capacity to maintain accurate protein folding, and has been implicated in creating drug-resistance in several solid tumors. Objective: To identify the role of ER-stress and lipid metabolism in mediating drug response in HCC. Methods: By using a chemically-induced mouse model for HCC, we administered the ER-stress inhibitor 4m8C and/or doxorubicin (DOX) twice weekly for three weeks post-tumor initiation. Histological analyses were performed alongside comprehensive molecular biology and lipidomics assessments of isolated liver samples. In vitro models, including HCC cells, spheroids, and patient-derived liver organoids were subjected to 4m8C and/or DOX, enabling us to assess their synergistic effects on cellular viability, lipid metabolism, and oxygen consumption rate. Results: We reveal a pivotal synergy between ER-stress modulation and drug response in HCC. The inhibition of ER-stress using 4m8C not only enhances the cytotoxic effect of DOX, but also significantly reduces cellular lipid metabolism. This intricate interplay culminates in the deprivation of energy reserves essential for the sustenance of tumor cells. Conclusions: This study elucidates the interplay between lipid metabolism and ER-stress modulation in enhancing doxorubicin efficacy in HCC. This novel approach not only deepens our understanding of the disease, but also uncovers a promising avenue for therapeutic innovation. The long-term impact of our study could open the possibility of ER-stress inhibitors and/or lipase inhibitors as adjuvant treatments for HCC-patients. (c) 2023 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 11. |
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| 12. |
- Koutsouveli, Vasiliki, et al.
(author)
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Oogenesis and lipid metabolism in the deep-sea sponge Phakellia ventilabrum (Linnaeus, 1767)
- 2022
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 6317-
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Journal article (peer-reviewed)abstract
- Sponges contain an astounding diversity of lipids that serve in several biological functions, including yolk formation in their oocytes and embryos. The study of lipid metabolism during reproduction can provide information on food-web dynamics and energetic needs of the populations in their habitats, however, there are no studies focusing on the lipid metabolism of sponges during their seasonal reproduction. In this study, we used histology, lipidome profiling (UHPLC-MS), and transcriptomic analysis (RNA-seq) on the deep-sea sponge Phakellia ventilabrum (Demospongiae, Bubarida), a key species of North-Atlantic sponge grounds, with the goal to (i) assess the reproductive strategy and seasonality of this species, (ii) examine the relative changes in the lipidome signal and the gene expression patterns of the enzymes participating in lipid metabolism during oogenesis. Phakellia ventilabrum is an oviparous and most certainly gonochoristic species, reproducing in May and September in the different studied areas. Half of the specimens were reproducing, generating two to five oocytes per mm2. Oocytes accumulated lipid droplets and as oogenesis progressed, the signal of most of the unsaturated and monounsaturated triacylglycerides increased, as well as of a few other phospholipids. In parallel, we detected upregulation of genes in female tissues related to triacylglyceride biosynthesis and others related to fatty acid beta-oxidation. Triacylglycerides are likely the main type of lipid forming the yolk in P. ventilabrum since this lipid category has the most marked changes. In parallel, other lipid categories were engaged in fatty acid beta-oxidation to cover the energy requirements of female individuals during oogenesis. In this study, the reproductive activity of the sponge P. ventilabrum was studied for the first time uncovering their seasonality and revealing 759 lipids, including 155 triacylglycerides. Our study has ecological and evolutionary implications providing essential information for understanding the molecular basis of reproduction and the origins and formation of lipid yolk in early-branching metazoans.
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| 13. |
- Kullenberg, Fredrik, et al.
(author)
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In Vitro Cell Toxicity and Intracellular Uptake of Doxorubicin Exposed as a Solution or Liposomes : Implications for Treatment of Hepatocellular Carcinoma
- 2021
-
In: Cells. - : MDPI. - 2073-4409. ; 10:7
-
Journal article (peer-reviewed)abstract
- Cytostatic effects of doxorubicin in clinically applied doses are often inadequate and limited by systemic toxicity. The main objective of this in vitro study was to determine the anti-tumoral effect (IC50) and intracellular accumulation of free and liposomal doxorubicin (DOX) in four human cancer cell lines (HepG2, Huh7, SNU449 and MCF7). The results of this study showed a correlation between longer DOX exposure time and lower IC50 values, which can be attributed to an increased cellular uptake and intracellular exposure of DOX, ultimately leading to cell death. We found that the total intracellular concentrations of DOX were a median value of 230 times higher than the exposure concentrations after exposure to free DOX. The intracellular uptake of DOX from solution was at least 10 times higher than from liposomal formulation. A physiologically based pharmacokinetic model was developed to translate these novel quantitative findings to a clinical context and to simulate clinically relevant drug concentration-time curves. This showed that a liver tumor resembling the liver cancer cell line SNU449, the most resistant cell line in this study, would not reach therapeutic exposure at a standard clinical parenteral dose of doxorubicin (50 mg/m(2)), which is serious limitation for this drug. This study emphasizes the importance of in-vitro to in-vivo translations in the assessment of clinical consequence of experimental findings.
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| 14. |
- Montero, Olimpio, et al.
(author)
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Trials and tribulations of statistical significance in biochemistry and omics
- 2023
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In: TIBS -Trends in Biochemical Sciences. Regular ed.. - : Elsevier. - 0968-0004 .- 1362-4326. ; 48:6, s. 503-512
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Journal article (other academic/artistic)abstract
- Over recent years many statisticians and researchers have highlighted that statis-tical inference would benefit from a better use and understanding of hypothesis testing, p-values, and statistical significance. We highlight three recommendations in the context of biochemical sciences. First recommendation: to improve the bio-logical interpretation of biochemical data, do not use p-values (or similar test statis-tics) as thresholded values to select biomolecules. Second recommendation: to improve comparison among studies and to achieve robust knowledge, perform complete reporting of data. Third recommendation: statistical analyses should be reported completely with exact numbers (not as asterisks or inequalities). Owing to the high number of variables, a better use of statistics is of special importance in omic studies.
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| 15. |
- Nilsson, Jenny M., et al.
(author)
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Ammonium bicarbonate buffers combined with hybrid surface technology columns improve the peak shape of strongly tailing lipids
- 2024
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In: Analytica Chimica Acta. - : Elsevier. - 0003-2670 .- 1873-4324. ; 1316
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Journal article (peer-reviewed)abstract
- Background: Lipids such as phosphatidic acids (PAs) and cardiolipins (CLs) present strongly tailing peaks in reversed phase liquid chromatography, which entails low detectability. They are usually analyzed by hydrophilic interaction liquid chromatography (HILIC), which hampers high-throughput lipidomics. Thus, there is a great need for improved analytical methods in order to obtain a broader coverage of the lipidome in a single chromatographic method. We investigated the effect of ammonium bicarbonate (ABC) on peak asymmetry and detectability, in comparison with ammonium formate (AFO) on both a conventional BEH C18 column and an HST-CSH C18 column.Results: The combination of 2.5 mM ABC buffer pH 8 with an HST-CSH C18 column produced significantly improved results, reducing the asymmetry factor at 10 % peak height of PA 16:0/18:1 from 8.4 to 1.6. Furthermore, on average, there was up to a 54-fold enhancement in the peak height of its [M - H]- ion compared to AFO and the BEH C18 column. We confirmed this beneficial effect on other strongly tailing lipids, with accessible phosphate moieties e.g., cardiolipins, phosphatidylinositol phosphate, phosphatidylinositol bisphosphate, phosphorylated ceramide and phosphorylated sphingosine. Furthermore, we found an increased detectability of phospho- and sphingolipids up to 28 times in negative mode when using an HST-CSH C18 column. The method was successfully applied to mouse liver samples, where previously undetected endogenous phospholipids could be analyzed with improved chromatographic separation.Significance: In conclusion, the use of 2.5 mM ABC substantially improved the peak shape of PAs and enhanced the detectability of the lipidome in negative mode on an RPLC-ESI-Q-TOF-MS system on both BEH C18 and HSTCSH C18 columns. This method provides a wider coverage of the lipidome with one single injection for future lipidomic applications in negative mode.
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| 16. |
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| 17. |
- Palo Nieto, Carlos, et al.
(author)
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Developing reactive oxygen species-sensitive cellulose nanofibers for chronic wound care
- 2022
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Conference paper (peer-reviewed)abstract
- There is an increasing interest in developing bio-responsive materials using reactive oxygen species (ROS) as biological stimulus.1 These materials, with the potential to be used in several biomedical applications, i.e. wound healing,2 should have the capacity to specifically reduce the excess of ROS at sites of inflammation and promote tissue healing. Wood derived cellulose nanofibrils (CNFs) have emerged as an interesting nanomaterial with highly tunable properties that could be of value for wound care applications. In our group, we have demonstrated the ability of CNF-based hydrogels to aid in the healing of acute wounds,3 being an excellent platform for the development of bioactive wound healing dressings. In the present work, ROS-sensitive peptides were covalently incorporated into carboxymethylated CNFs (c-CNF) using two well-known chemical reactions; amine coupling through EDC/NHS activation and reductive amination. The obtained materials were characterized in terms of chemical structure (CP/MAS 13C-NMR spectroscopy), degree of substitution (elemental analysis of nitrogen content) and degree of crosslinking (ninhydrin test).The new synthetized biomaterials (figure 1) showed susceptibility to an oxidative environment and their ROS scavenging properties were confirmed by their cell-protective effect in the presence of high levels of ROS. These results serve as an excellent starting point for the development of CNF-based dressings capable of promoting the resolution of chronic wounds.
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| 18. |
- Palo-Nieto, Carlos, 1985-, et al.
(author)
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Functionalization of cellulose nanofibrils to develop novel ROS-sensitive biomaterials
- 2023
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In: Materials Advances. - : Royal Society of Chemistry. - 2633-5409. ; 4:6, s. 1555-1565
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Journal article (peer-reviewed)abstract
- Wood derived cellulose nanofibrils (CNFs) have emerged as an interesting material for biomedical applications. Functionalization of the nanofibrils with bioactive molecules is a potent tool to tailor CNF materials for specific applications in biomedicine. The present work proposes the functionalization of CNFs with a reactive oxygen species (ROS)-sensitive oligopeptide to develop a novel CNF-based material for the treatment of medical conditions associated with high levels of ROS such as chronic wounds. Oligoproline peptides of two different lengths (5 and 10 proline units) were covalently incorporated onto the CNF surface, several water-based chemical approaches were explored and the reaction conditions to maximize peptide substitution and the degree of fibre crosslinking were optimized. The chemical structure, degree of peptide substitution, degree of fibre crosslinking, surface morphology and ROS-sensitivity of the oligoproline–CNF materials were characterized. Double-crosslinked CNF hydrogels (Ca2+–oligoproline–CNF) were further prepared and the ability of the hydrogels to protect cells from an oxidative environment was investigated in vitro with human dermal fibroblasts, as a first evaluation of the potential of the novel CNF material to be used in chronic wound therapies. Optimization of the reaction conditions resulted in a degree of peptide substitution of 102 ± 10 μmol g−1 CNF irrespective of the oligoproline length and a degree of crosslinking of 55–80% depending on the number of proline units. The results showed that the oligoproline covalently attached to CNFs via carbodiimide chemistry maintained its ability to respond to ROS and that the responsiveness in terms of viscoelastic properties depended on the length of the oligopeptide, with the hydrogel being more responsive when functionalized with 10 proline units compared with 5 proline units. Furthermore, the double crosslinked Ca2+–oligoproline–CNF hydrogels promoted the survival of human dermal fibroblasts exposed to high levels of ROS. This study is the first one to provide an insight into the development of ROS-sensitive materials based on CNFs and opens up possibilities for further investigation on the use of these novel materials in chronic wound care.
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| 19. |
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| 20. |
- Pirttilä, Kristian, et al.
(author)
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Comprehensive Peak Characterization (CPC) in Untargeted LC–MS Analysis
- 2022
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In: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 12:2
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Journal article (peer-reviewed)abstract
- LC–MS-based untargeted metabolomics is heavily dependent on algorithms for automated peak detection and data preprocessing due to the complexity and size of the raw data generated. These algorithms are generally designed to be as inclusive as possible in order to minimize the number of missed peaks. This is known to result in an abundance of false positive peaks that further complicate downstream data processing and analysis. As a consequence, considerable effort is spent identifying features of interest that might represent peak detection artifacts. Here, we present the CPC algorithm, which allows automated characterization of detected peaks with subsequent filtering of low quality peaks using quality criteria familiar to analytical chemists. We provide a thorough description of the methods in addition to applying the algorithms to authentic metabolomics data. In the example presented, the algorithm removed about 35% of the peaks detected by XCMS, a majority of which exhibited a low signal-to-noise ratio. The algorithm is made available as an R-package and can be fully integrated into a standard XCMS workflow.
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| 21. |
- Velasco, Marta, et al.
(author)
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Ammonia Concentration in the Eluent Influences Fragmentation Pattern of Triacylglycerols in Mass Spectrometry Analysis
- 2022
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In: Metabolites. - : MDPI. - 2218-1989 .- 2218-1989. ; 12:5
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Journal article (peer-reviewed)abstract
- Correct assessment of the fatty acyl at the glycerol sn-2 position in triacylglycerol (TAG) analysis by liquid chromatography and mass spectrometry (LC-MS) is challenging. Ammonium hydroxide (NH4OH) is the preferred choice for the solvent additive for the formation of the ammonium adduct ([M + NH4](+)). In this study, the influence of different NH4OH concentrations in the eluents on TAG adduct formation and fragmentation under LC-MS analysis was assessed. Increasing NH4OH concentrations delayed the chromatographic elution time according to a power function. The [M + NH4](+) and [M + ACN + NH4](+) adducts (where ACN means acetonitrile) were formed at all ammonium concentrations assayed. [M + ACN + NH4](+) predominated above 18.26 mM [NH4OH], and the intensity of [M + NH4](+) dropped. TAG fragmentation for fatty acyl release in the MSE was reduced with increasing [M + ACN + NH4](+) adduct, which suggests that ACN stabilizes the adduct in a way that inhibits the rupture of the ester bonds in TAGs. A linear equation (Hsn-I = a x H[M+NH4]+, where sn-I refers to the sn position of the glycerol (I = 1, 2, or 3) and H is the peak height) was deduced to quantify the dehydroxydiacylglycerol fragment intensity in relation to [M + NH4](+) intensity in the full scan. This equation had a slope mean value of 0.369 +/- 0.058 for the sn-1 and sn-3 positions, and of 0.188 +/- 0.007 for the sn-2 position.
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