PubMed

Nat Commun. 2022 Nov 21;13(1):7024. doi: 10.1038/s41467-022-34422-2.ABSTRACTEnvironmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1301 mother-child pairs, we associate individual exposomes consisting of >100 chemical, outdoor, social and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, proteins and metabolites) in childhood. We identify 1170 associations, 249 in pregnancy and 921 in childhood, which reveal potential biological responses and sources of exposure. Pregnancy exposures, including maternal smoking, cadmium and molybdenum, are predominantly associated with child DNA methylation changes. In contrast, childhood exposures are associated with features across all omics layers, most frequently the serum metabolome, revealing signatures for diet, toxic chemical compounds, essential trace elements, and weather conditions, among others. Our comprehensive and unique resource of all associations ( https://helixomics.isglobal.org/ ) will serve to guide future investigation into the biological imprints of the early life exposome.PMID:36411288 | DOI:10.1038/s41467-022-34422-2

Trends Plant Sci. 2022 Nov 18:S1360-1385(22)00294-1. doi: 10.1016/j.tplants.2022.10.009. Online ahead of print.NO ABSTRACTPMID:36411181 | DOI:10.1016/j.tplants.2022.10.009

J Agric Food Chem. 2022 Nov 21. doi: 10.1021/acs.jafc.2c05940. Online ahead of print.ABSTRACTAn effective identification and discovery of fungal pigments is very important to illustrate the role of fungal pigments in the life process and conduce to the discovery of new bioactive and edible pigments. The phenotype combined with metabolomic and genomic (PMG) strategy led to the discovery and characterization of three new sorbicillinoid pigments, stasorbicillinoids A-C (1-3), and five known analogues (4-8) from the sponge-derived fungus Stagonospora sp. SYSU-MS7888. Their structures were elucidated by the application of spectroscopic methods (NMR, MS, UV, IR, and ECD) and modified Mosher's method. Compounds 1 and 2 featured novel naphthone nuclei linked by two alkyl side chains possibly undergoing inter- and intramolecular Michael reactions. Compounds 1-8 exhibited potent anti-inflammatory activity with IC50 values in the range of 3.56-22.8 μM. Furthermore, compound 2 inhibited the production of IL-1β, IL-6, and TNF-α in a dose-dependent manner. This study provides an effective strategy to accelerate the discovery of new fungal pigments and further exploration of their potential applications in different fields such as medicine and food industries.PMID:36410725 | DOI:10.1021/acs.jafc.2c05940

J Agric Food Chem. 2022 Nov 21. doi: 10.1021/acs.jafc.2c06802. Online ahead of print.ABSTRACTThe effect of nonacylated and acylated anthocyanins on urinary metabolites in diabetic rats was investigated. Nonacylated anthocyanins extract from bilberries (NAAB) or acylated anthocyanins extract from purple potatoes (AAPP) was given to Zucker diabetic fatty (ZDF) rats for 8 weeks at daily doses of 25 and 50 mg/kg body weight. 1H NMR metabolomics was applied to study alterations in urinary metabolites from three time points (weeks 1, 4, and 8). Both types of anthocyanins modulated the metabolites associated with the tricarboxylic acid cycle, gut microbiota metabolism, and renal function at weeks 1 and 4, such as 2-oxoglutarate, fumarate, alanine, trigonelline, and hippurate. In addition, only a high dose of AAPP decreased monosaccharides, formate, lactate, and glucose levels at week 4, suggesting improvement in energy production in mitochondria, glucose homeostasis, and oxidative stress. This study suggested different impacts of AAPP and NAAB on the metabolic profile of urine in diabetes.PMID:36410712 | DOI:10.1021/acs.jafc.2c06802

Osteoarthritis Cartilage. 2022 Nov 18:S1063-4584(22)00927-X. doi: 10.1016/j.joca.2022.11.004. Online ahead of print.ABSTRACTOBJECTIVES: Metabolic pathways are a series of chemical reactions by which cells take in nutrient substrates for energy and building blocks needed to maintain critical cellular processes. Details of chondrocyte metabolism and how it rewires during the progression of osteoarthritis (OA) are unknown. This research aims to identify what changes in the energy metabolic state occur in OA cartilage.METHODS: Patient matched OA and non-OA cartilage specimens were harvested from total knee replacement patients. Cartilage was first collected for metabolomics, proteomics, and transcriptomics analyses to study global alterations in OA metabolism. We then determined the metabolic routes by tracking [U-13C] isotope with liquid chromatography-mass spectrometry (LC-MS). We further evaluated cellular bioenergetic profiles by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) and investigated the effects of low-dose and short-term effects of 2-deoxyglucose (2DG) on chondrocytes.RESULTS: OA chondrocytes showed increased basal ECAR and more lactate production compared to non-OA chondrocytes. [U-13C] glucose labelling revealed that less glucose-derived carbon entered the TCA cycle. On the other hand, mitochondrial respiratory rates were markedly decreased in the OA chondrocytes compared to non-OA chondrocytes. These changes were accompanied by decreased cellular ATP production, mitochondrial membrane potential and disrupted mitochondrial morphology. We further demonstrated in vitro that short-term inhibition of glycolysis suppressed matrix degeneration gene expression in chondrocytes and bovine cartilage explants cultured under inflammatory conditions.CONCLUSION: This study represents the first comprehensive comparative analysis of metabolism in OA chondrocytes and lays the groundwork for therapeutic targeting of metabolism in OA.PMID:36410637 | DOI:10.1016/j.joca.2022.11.004

J Ethnopharmacol. 2022 Nov 18:115931. doi: 10.1016/j.jep.2022.115931. Online ahead of print.ABSTRACTETHNOPHARMACOLOGY RELEVANT: "Four Natures and five "Flavors" comes from the high generalization of medicine pharmacological rules from clinical practice by ancients. "Flavor" and "Natures"are both descriptions of the effect properties of traditional Chinese medicine. At present, researchers have realized that the "Flavors" (Pungent, Sour, Sweet, Bitter and Salty) are related to the different pharmacological effects of treatment. The "Natures" (Warm, Hot, Cold and Cool) are closely related to energy and substance metabolism and contribute to the effect of the "Flavors". Since "Four Natures and five Flavors" are the rules derived from clinical practice, how to describe and characterize "Natures" and "Flavors" scientifically is still a problem that needs to be solved.AIM OF THE STUDY: the aim is to objectively further understand the scientific connotations of properties ("Flavors"and "Natures") from the perspective of metabolomics and characterize them by metabolites.MATERIALS AND METHOD: "Pungent-Neutral", "Sweet-Neutral and "Bitter-Neutral" TCMs were selected to characterize the "Flavors" (Pungent, Sweet and Bitter). "Pungent-Warm" and "Bitter-Cold" were selected to characterize the "Natures" (Warm and Cold). The rat serum metabolomics was performed on UHPLC-Q-Exactive. Metabolites were identified through the metabolites databases and related literature.RESULTS: The "Flavors" and "Natures" metabolites were identified, respectively, including four "Pungent", four "Sweet" and thirteen "Bitter" characterized metabolites and thirteen "Cold" and sixteen "Warm"related metabolites.CONCLUSIONS: The "Natures" characterized metabolites show the "Natures" are closely related to lipid and energy metabolism. The "Warm" may promote lipid metabolism to produce ATP to generate energy through bile acid metabolism and purine metabolism. The "Cold" may inhibit lipid metabolism to generate ATP to decrease energy through the way of tryptophan metabolism and purine metabolism. The "Flavors" characteristic metabolites can provide a theoretical basis for the rules of the "Flavors". These metabolites can also be used to characterize TCM's "Natures" and "Flavors" in the development of traditional Chinese medicine resources and quality control.PMID:36410573 | DOI:10.1016/j.jep.2022.115931

Int J Cardiol. 2022 Nov 18:S0167-5273(22)01711-9. doi: 10.1016/j.ijcard.2022.11.024. Online ahead of print.ABSTRACTBACKGROUND: Type III hyperlipidaemia (T3HL) is characterised by equimolar increases in plasma triglycerides (TG) and cholesterol in <10% of APOE22 carriers conveying high cardiovascular disease (CVD) risk. We investigate the role of a weighted triglyceride-raising polygenic score (TG.PS) precipitating T3HL.METHODS: The TG.PS (restricted to genome-wide significance and weighted by published independent effect estimates) was applied to the Oxford Biobank (OBB, n = 6952) and the UK Biobank (UKB, n = 460,037), to analyse effects on plasma lipid phenotypes. Fasting plasma lipid, lipoprotein biochemistry and NMR lipoprotein profiles were analysed in OBB. CVD prevalence/incidence was examined in UKB.RESULTS: One TG.PS standard-deviation (SD) was associated with 13.0% (95% confidence-interval 12.0-14.0%) greater TG in OBB and 15.2% (15.0-15.4%) in UKB. APOE22 carriers had 19.0% (1.0-39.0%) greater TG in UKB. Males were more susceptible to TG.PS effects (4.0% (2.0-6.0%) greater TG with 1 TG.PS SD in OBB, 1.6% (1.3-1.9%) in UKB) than females. There was no interaction between APOE22 and TG.PS, BMI, sex or age on TG. APOE22 carriers had lower apolipoprotein B (apoB) (OBB; -0.35 (-0.29 to -0.40)g/L, UKB; -0.41 (-0.405 to -0.42)g/L). NMR lipoprotein lipid concentrations were discordant to conventional biochemistry in APOE22 carriers. In APOE22 compared with APOE33, CVD was no more prevalent in similarly hypertriglyceridaemic participants (OR 0.97 95%CI 0.76-1.25), but was less prevalent in normolipidaemia (OR 0.81, 95%CI 0.69-0.95); no differences were observed in CVD incidence.CONCLUSIONS: TG.PS confers an additive risk for developing T3HL, that is of comparable effect size to conventional risk factors. The protective effect of APOE22 for prevalent CVD is consistent with lower apoB in APOE22 carriers.PMID:36410544 | DOI:10.1016/j.ijcard.2022.11.024

Sci Total Environ. 2022 Nov 18:160372. doi: 10.1016/j.scitotenv.2022.160372. Online ahead of print.ABSTRACTAmmonia is a common pollutant in aquaculture system, and toxic to all aquatic animals. However, different aquatic animals exhibit diverse physiological responses to high-level ammonia exposure, potentially indicating their divergent resistance to ammonia stress. In this study, juveniles of three freshwater turtles (Mauremys reevesii, Pseudemys nelsoni and Trachemys scripta elegans) were exposed to different concentrations of ammonia (0, 0.3 and 3.0 mg/L) for 30 days, and their swimming, growth performance, gut microbiota, and hepatic metabolites were measured to evaluate the interspecific difference in physiological responses to ammonia stress. Despite no differences in swimming ability, growth rate, and gut microbial diversity, observable changes in microbial community composition and hepatic metabolite profiles were shown in ammonia-exposed turtles. A relatively higher abundance of potentially pathogenic bacteria was found in M. reevesii than in the other two species. Moreover, microbial compositions and metabolic responses differed significantly among the three species. M. reevesii was, out of the three tested species, the one in which exposure to ammonia had the greatest effect on changes in bacterial genera and hepatic metabolites. Conversely, only a few metabolites were significantly changed in T. scripta elegans. Integrating these findings, we speculated that native M. reevesii should be more vulnerable to ammonia stress compared to the invasive turtle species. Our results plausibly reflected divergent potential resistance to ammonia among these turtles, in view of differential physiological responses to ammonia exposure at environmentally relevant concentrations.PMID:36410481 | DOI:10.1016/j.scitotenv.2022.160372

J Autoimmun. 2022 Nov 18;133:102953. doi: 10.1016/j.jaut.2022.102953. Online ahead of print.ABSTRACTAntineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises a group of multisystem disorders involving severe, systemic, small-vessel vasculitis with short- and long term serious and life-threating complications. Despite the simplification of treatment, fundamental aspects concerning assessment of its efficacy and its adaptation to encountered complications or to the relapsing/remitting/subclinical disease course remain still unknown. The pathogenesis of AAV is complex and unique, and despite the progress achieved in the last years, much has not to be learnt. Foremost, there is still no accurate marker enabling us to monitoring disease and guide therapy. Therefore, the disease management relays often on clinical judgment and follows a" trial and error approach". In the recent years, an increasing number of new molecules s have been explored and used for this purpose including genomics, B- and T-cell subpopulations, complement system factors, cytokines, metabolomics, biospectroscopy and components of our microbiome. The aim of this review is to discuss both the role of known historical and clinically established biomarkers of AAV, as well as to highlight potential new ones, which could be used for timely diagnosis and monitoring of this devastating disease, with the goal to improve the effectiveness and ameliorate the complications of its demanding therapy.PMID:36410262 | DOI:10.1016/j.jaut.2022.102953

Int J Parasitol Drugs Drug Resist. 2022 Nov 11;20:135-144. doi: 10.1016/j.ijpddr.2022.11.001. Online ahead of print.ABSTRACTNew antimalarial compounds with novel mechanisms of action are urgently needed to combat the recent rise in antimalarial drug resistance. Phenotypic high-throughput screens have proven to be a successful method for identifying new compounds, however, do not provide mechanistic information about the molecular target(s) responsible for antimalarial action. Current and emerging target identification methods such as in vitro resistance generation, metabolomics screening, chemoproteomic approaches and biophysical assays measuring protein stability across the whole proteome have successfully identified novel drug targets. This review provides an overview of these techniques, comparing their strengths and weaknesses and how they can be utilised for antimalarial target identification.PMID:36410177 | DOI:10.1016/j.ijpddr.2022.11.001

Biomed Pharmacother. 2022 Nov 18;157:114002. doi: 10.1016/j.biopha.2022.114002. Online ahead of print.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) pathogenesis is affected by dysbiosis of the gut microbiome and the metabolites it generates. Therefore, restoring the equilibrium between the gut microbiome and the generated metabolites may have therapeutic potential for the syndrome. Zuogui Jiangtang Qinggan Fang (ZGJTQGF) is a Chinese herbal formulation used clinically to treat type 2 diabetic mellitus (T2DM) and fatty liver disease. However, its pharmacological mechanisms have not been well characterized. This work aimed to evaluate the hepatoprotective mechanism of ZGJTQGF in T2DM with NAFLD mice by incorporating gut microbiota, short-chain fatty acids（SCFAs）, and metabolomic analysis, and then to provide strong support for clinical treatment of T2DM with NAFLD. The sequencing of 16 S rRNA revealed that ZGJTQGF therapy modified the composition and abundance of the gut microbiome, raised the level of SCFAs, and restored the intestinal mucosal barrier. The non-targeted metabolomic analysis of liver tissues identified 212 compounds, of which108 were differentially expressed between the HFD and ZGJTQGF groups. Moreover, L-glutamic acid, L-Phenylalanine, Glycine, Taurine, Deoxycholic acid, and citric acid levels were also considerably altered by ZGJTQGF. Our findings suggest that ZGJTQGF ameliorates HFD-induced hepatic steatosis by modulating the gut microbiota composition and its metabolites and boosting the levels of SCFAs. More notably, ZGJTQGF may be a promising medication for preventing and treating NAFLD.PMID:36410120 | DOI:10.1016/j.biopha.2022.114002

Phytomedicine. 2022 Nov 11;108:154546. doi: 10.1016/j.phymed.2022.154546. Online ahead of print.ABSTRACTBACKGROUND: Chronic kidney disease (CKD) is challenging to reverse and its treatment options are limited. Yishen-Qingli-Huoxue Formula (YQHF) is an effective treatment Chinese formula for CKD, as verified by clinical randomized controlled trial. However, the correlative YQHF therapeutic mechanisms are still unknown.PURPOSE: The current study aimed to investigate the potential anti-renal fibrosis effects of YQHF as well as the underlying mechanism.METHODS: After affirming the curative effects of YQHF on adenine-induced CKD rats, Masson staining, immunohistochemistry, and ELISA were used to assess the effects of YQHF on renal fibrosis. Subsequently, metabolomics and transcriptomics analyses were conducted to clarify the potential mechanisms. Furthermore, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), molecular docking analysis and in vitro experiments were used to verify final mechanism of anti-fibrosis.RESULTS: Our results demonstrated that YQHF could improve renal morphology, decrease blood urea nitrogen (BUN), serum creatinine (Scr), and increase body weight gain of model rats. Masson staining, immunohistochemistry of collagen I, fibronectin (FN), α-smooth muscle actin (α-SMA), vimentin and E-cadherin showed that YQHF delayed CKD progression by alleviating renal fibrosis, and the expression of fibrotic factors smoc2 and cdh11 were obviously suppressed by YQHF. Metabolomic and transcriptomic measures discovered that indoxyl sulfate might be a crucial factor inducing renal fibrosis, and the antagonistic effect of YQHF on renal fibrosis may be exerted via AhR/snai1 signaling. Subsequently, western blot and immunohistochemical experiments revealed YQHF indeed inhibited AhR/snai1 signaling in adenine-induced renal fibrosis of CKD rat, which confirmed previous results. In addition, molecular docking and in vitro experiments further supported this conclusion, in which astilbin, the main compound identified YQHF, was certified to exert a significant effect on AhR.CONCLUSION: Our findings showed that YQHF can effectively treat CKD by antagonizing renal fibrosis, the potential mechanisms were relating with the regulation on AhR/snai1 signaling.PMID:36410103 | DOI:10.1016/j.phymed.2022.154546

Cancer Res. 2022 Nov 21:CAN-22-0677. doi: 10.1158/0008-5472.CAN-22-0677. Online ahead of print.ABSTRACTGlioblastoma (GBM) is a common and deadly form of brain tumor in adults. Dysregulated metabolism in GBM offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome, and the glycoproteome of human subgroup-specific GBM sphere-forming cells (GSCs). L-fucose abundance and core fucosylation activation were elevated in mesenchymal (MES) compared to proneural (PN) GSCs; this pattern was retained in subgroup-specific xenografts and in subgroup-affiliated human patient samples. Genetic and pharmacological inhibition of core fucosylation significantly reduced tumor growth in MES GBM preclinical models. Liquid chromatography-mass spectrometry (LC-MS)-based glycoproteomic screening indicated that most MES-restricted core fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion, and integrin-mediated signaling. Selective L-fucose accumulation in MES GBMs was observed using pre-clinical minimally-invasive positron emission tomography (PET), implicating this metabolite as a potential subgroup-restricted biomarker. Overall, these findings indicate that L-fucose pathway activation in MES GBM is a subgroup-specific dependency that could provide diagnostic markers and actionable therapeutic targets.PMID:36409826 | DOI:10.1158/0008-5472.CAN-22-0677

Cancer Res. 2022 Nov 21:CAN-22-0423. doi: 10.1158/0008-5472.CAN-22-0423. Online ahead of print.ABSTRACTInflammatory breast cancer (IBC) is a difficult-to-treat disease with poor clinical outcomes due to high risk of metastasis and resistance to treatment. In breast cancer, CD44+CD24- cells possess stem cell-like features and contribute to disease progression, and we previously described a CD44+CD24-pSTAT3+ breast cancer cell subpopulation that is dependent on JAK2/STAT3 signaling. Here we report that CD44+CD24- cells are the most frequent cell-type in IBC and are commonly pSTAT3+. Combination of JAK2/STAT3 inhibition with paclitaxel decreased IBC xenograft growth more than either agent alone. IBC cell lines resistant to paclitaxel and doxorubicin were developed and characterized to mimic therapeutic resistance in patients. Multi-omic profiling of parental and resistant cells revealed enrichment of genes associated with lineage identity and inflammation in chemotherapy resistant derivatives. Integrated pSTAT3 ChIP-seq and RNA-seq analyses showed pSTAT3 regulates genes related to inflammation and epithelial to mesenchymal transition (EMT) in resistant cells, as well as PDE4A, a cAMP-specific phosphodiesterase. Metabolomic characterization identified elevated cAMP signaling and CREB as a candidate therapeutic target in IBC. Investigation of cellular dynamics and heterogeneity at the single cell level during chemotherapy and acquired resistance by CyTOF and single cell RNA-seq identified mechanisms of resistance including a shift from luminal to basal/mesenchymal cell states through selection for rare pre-existing subpopulations or an acquired change. Lastly, combination treatment with paclitaxel and JAK2/STAT3 inhibition prevented the emergence of the mesenchymal chemo-resistant subpopulation. These results provide mechanistic rational for combination of chemotherapy with inhibition of JAK2/STAT3 signaling as a more effective therapeutic strategy in IBC.PMID:36409824 | DOI:10.1158/0008-5472.CAN-22-0423

Diabetes. 2022 Nov 21:db23er02a. doi: 10.2337/db23-er02a. Online ahead of print.ABSTRACTIn the article cited above, affiliation 6 was incorrectly listed as "Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China" due to a composition error. The correct affiliation 6 is "Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China." The editors apologize for the error. The online version of the article (https://doi.org/10.2337/db22-0260) has been updated to correct the affiliation.PMID:36409587 | DOI:10.2337/db23-er02a

J Clin Invest. 2022 Nov 21:e163472. doi: 10.1172/JCI163472. Online ahead of print.ABSTRACTBACKGROUND: The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanism underlying delirium, particularly in relation to the KP, remain elusive.METHODS: We undertook a multi-center observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and one-year mortality.RESULTS: In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA, OR 2.26 [1.78, 2.87], p<0.001) to be increased, as well as increases in several other KP metabolites in serum and CSF. In addition, CSF-QA was associated with the neuronal damage marker neurofilament light chain (NfL, β 0.43, p<0.001) and was a strong predictor of one-year mortality (HR 4.35 [2.93, 6.45] for CSF-QA ≥ 100 nmol/L, p<0.001). The associations between CSF-QA and delirium, neuronal damage, and mortality remained highly significant following adjustment for confounders and multiple comparisons.CONCLUSION: Our data identified how systemic inflammation, neurotoxicity, and delirium are strongly linked via the KP, and should inform future delirium prevention and treatment clinical trials that target enzymes of the KP.FUNDING: Norwegian Health Association and the South-Eastern Norway Regional Health Authorities.PMID:36409557 | DOI:10.1172/JCI163472

Rapid Commun Mass Spectrom. 2022 Nov 21:e9437. doi: 10.1002/rcm.9437. Online ahead of print.ABSTRACTRATIONALE: Databases of electron ionization mass spectra are often used in GC/MS-based untargeted metabolomics analysis. The results of the library search depend on several factors such as the size and quality of the database, the library search algorithm, and etc. We found out that the list of considered m/z values is another important parameter. Unfortunately, this information is not usually specified by software developers, and it is hidden from the end user.METHODS: We created synthetic data sets and figured out how several popular software products (AMDIS, ChromaTOF, MS Search, and Xcalibur) select the list of m/z values for the library search. Moreover, we considered data sets of real mass spectra (presented in both NIST and FiehnLib libraries) and compared the library search results obtained within different software products. All programs under consideration call the NIST MS Search binaries to perform the library search using the Identity algorithm.RESULTS: We found out that AMDIS and ChromaTOF can give biased library search results under particular conditions. In untargeted metabolomics, it can happen when NIST and FiehnLib libraries are used simultaneously, the scan range of the instrument is less than 85, and the correct answer is present only in the FiehnLib library.CONCLUSIONS: The main reason for biased results is that the information about the scan range is not stored in the metadata of library records. As a result, in the case of AMDIS and ChromaTOF software, some unrecorded peaks are considered as missing ones during the library search, the respective compound is penalized, and the correct answer falls outside the top 5 or even 10 hits. At the same time, the default algorithm for selecting the list of considered m/z values implemented in MS Search is free from such unexpected behavior.PMID:36409456 | DOI:10.1002/rcm.9437

Metabolomics. 2022 Nov 19;18(12):94. doi: 10.1007/s11306-022-01947-y.ABSTRACTBACKGROUND: Spectral library searching is currently the most common approach for compound annotation in untargeted metabolomics. Spectral libraries applicable to liquid chromatography mass spectrometry have grown in size over the past decade to include hundreds of thousands to millions of mass spectra and tens of thousands of compounds, forming an essential knowledge base for the interpretation of metabolomics experiments.AIM OF REVIEW: We describe existing spectral library resources, highlight different strategies for compiling spectral libraries, and discuss quality considerations that should be taken into account when interpreting spectral library searching results. Finally, we describe how spectral libraries are empowering the next generation of machine learning tools in computational metabolomics, and discuss several opportunities for using increasingly accessible large spectral libraries.KEY SCIENTIFIC CONCEPTS OF REVIEW: This review focuses on the current state of spectral libraries for untargeted LC-MS/MS based metabolomics. We show how the number of entries in publicly accessible spectral libraries has increased more than 60-fold in the past eight years to aid molecular interpretation and we discuss how the role of spectral libraries in untargeted metabolomics will evolve in the near future.PMID:36409434 | DOI:10.1007/s11306-022-01947-y

Metabolomics. 2022 Nov 19;18(12):95. doi: 10.1007/s11306-022-01958-9.ABSTRACTINTRODUCTION: Plant cell walls play an important role in providing physical strength and defence against abiotic stress. Rice brittle culm (bc) mutants are a strength-decreased mutant because of abnormal cell walls, and it has been reported that the causative genes of bc mutants affect cell wall composition. However, the metabolic alterations in each organ of bc mutants have remained unknown.OBJECTIVES: To evaluate the metabolic changes in rice bc mutants, comparative analysis of the primary metabolites was conducted.METHODS: The primary metabolites in leaves, internodes, and nodes of rice bc mutants and wild-type control were measured using CE- and LC-MS/MS. Multivariate analyses using metabolomic data was performed.RESULTS: We found that mutations in each bc mutant had different effects on metabolism. For example, higher oxalate content was observed in bc3 and bc1 bc3 mutants, suggesting that surplus carbon that was not used for cell wall components might be used for oxalate synthesis. In addition, common metabolic alterations such as a decrease of sugar nucleotides in nodes were found in bc1 and Bc6, in which the causative genes are involved in cellulose accumulation.CONCLUSION: These results suggest that metabolic analysis of the bc mutants could elucidate the functions of causative gene and improve the cell wall components for livestock feed or bioethanol production.PMID:36409428 | DOI:10.1007/s11306-022-01958-9

Handb Exp Pharmacol. 2022 Nov 22. doi: 10.1007/164_2022_617. Online ahead of print.ABSTRACTThe metabolome is composed of a vast array of molecules, including endogenous metabolites and lipids, diet- and microbiome-derived substances, pharmaceuticals and supplements, and exposome chemicals. Correct identification of compounds from this diversity of classes is essential to derive biologically relevant insights from metabolomics data. In this chapter, we aim to provide a practical overview of compound identification strategies for mass spectrometry-based metabolomics, with a particular eye toward pharmacologically-relevant studies. First, we describe routine compound identification strategies applicable to targeted metabolomics. Next, we discuss both experimental (data acquisition-focused) and computational (software-focused) strategies used to identify unknown compounds in untargeted metabolomics data. We then discuss the importance of, and methods for, assessing and reporting the level of confidence of compound identifications. Throughout the chapter, we discuss how these steps can be implemented using today's technology, but also highlight research underway to further improve accuracy and certainty of compound identification. For readers interested in interpreting metabolomics data already collected, this chapter will supply important context regarding the origin of the metabolite names assigned to features in the data and help them assess the certainty of the identifications. For those planning new data acquisition, the chapter supplies guidance for designing experiments and selecting analysis methods to enable accurate compound identification, and it will point the reader toward best-practice data analysis and reporting strategies to allow sound biological and pharmacological interpretation.PMID:36409330 | DOI:10.1007/164_2022_617