Advanced Methods for Natural Products Discovery: Bioactivity Screening, Dereplication, Metabolomics Profiling, Genomic Sequencing, Databases and Informatic Tools, and Structure Elucidation

Marine Drugs, Год журнала: 2023, Номер 21(5), С. 308 - 308

Опубликована: Май 19, 2023

Natural Products (NP) are essential for the discovery of novel drugs and products numerous biotechnological applications. The NP process is expensive time-consuming, having as major hurdles dereplication (early identification known compounds) structure elucidation, particularly determination absolute configuration metabolites with stereogenic centers. This review comprehensively focuses on recent technological instrumental advances, highlighting development methods that alleviate these obstacles, paving way accelerating towards Herein, we emphasize most innovative high-throughput tools advancing bioactivity screening, chemical analysis, dereplication, metabolite profiling, metabolomics, genome sequencing and/or genomics approaches, databases, bioinformatics, chemoinformatics, three-dimensional elucidation.

Язык: Английский

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Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Дек. 20, 2023

Abstract Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over past decade, majority acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect library, consisting 87,916 annotated derived from hundreds millions originating published experiments. Entries this or “suspects,” were that could be linked molecular network to an spectrum. Annotations propagated unknowns based on structural relationships reference molecules using MS/MS-based spectrum alignment. We demonstrate broad relevance library through representative examples propagation-based annotation acylcarnitines, bacterial and plant natural products, drug metabolism. Our results also highlight how can help better understand Alzheimer’s brain phenotype. The is openly available download data analysis GNPS platform investigators hypothesize candidate structures unknown data.

Язык: Английский

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Metabolomics and chemometrics: The next-generation analytical toolkit for the evaluation of food quality and authenticity

Trends in Food Science & Technology, Год журнала: 2024, Номер 147, С. 104481 - 104481

Опубликована: Апрель 7, 2024

The advances in NMR and mass spectrometry metabolomics allows a comprehensive profiling of foods, potentially covering geographical origin, authenticity, quality integrity issues. However, mining specific effects within the corresponding datasets is challenging due to presence set interacting factors that finally determine signatures. This review provides an overview different approaches used food then focusing on chemometric for data interpretation. In particular, interpretation hierarchically presented, starting from unsupervised (PCA, hierarchical clusters) supervised multivariate statistics like OPLS AMOPLS multiblock ANOVA discriminant approaches. Finally, machine learning Artificial Neural Networks are discussed as novel emerging tool support Tailored advisable, rather than unique solutions, with naively provide qualitative recognition patterns, modelling markers identification. Nonetheless, approach able interpretate complex

Язык: Английский

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Recent advances in mass spectrometry-based computational metabolomics

Current Opinion in Chemical Biology, Год журнала: 2023, Номер 74, С. 102288 - 102288

Опубликована: Март 24, 2023

The computational metabolomics field brings together computer scientists, bioinformaticians, chemists, clinicians, and biologists to maximize the impact of across a wide array scientific medical disciplines. continues expand as modern instrumentation produces datasets with increasing complexity, resolution, sensitivity. These must be processed, annotated, modeled, interpreted enable biological insight. Techniques for visualization, integration (within or between omics), interpretation data have evolved along innovation in databases knowledge resources required aid understanding. In this review, we highlight recent advances reflect on opportunities innovations response most pressing challenges. This review was compiled from discussions 2022 Dagstuhl seminar entitled "Computational Metabolomics: From Spectra Knowledge".

Язык: Английский

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Annotating metabolite mass spectra with domain-inspired chemical formula transformers

Nature Machine Intelligence, Год журнала: 2023, Номер 5(9), С. 965 - 979

Опубликована: Авг. 17, 2023

Язык: Английский

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Generating Molecular Fragmentation Graphs with Autoregressive Neural Networks

Analytical Chemistry, Год журнала: 2024, Номер 96(8), С. 3419 - 3428

Опубликована: Фев. 13, 2024

The accurate prediction of tandem mass spectra from molecular structures has the potential to unlock new metabolomic discoveries by augmenting community's libraries experimental reference standards. Cheminformatic spectrum strategies use a "bond-breaking" framework iteratively simulate fragmentations, but these methods are (a) slow due need exhaustively and combinatorially break molecules (b) inaccurate as they often rely upon heuristics predict intensity each resulting fragment; neural network alternatives mitigate computational cost black-box not inherently more accurate. We introduce physically grounded approach that learns breakage event score most relevant subset fragments quickly accurately. evaluate our model predicting both public private standard libraries, demonstrating hybrid offers state-of-the-art accuracy, improved metabolite identification database candidates, higher interpretability when compared previous networks. grounding in physical fragmentation events shows especially great promise for elucidating natural product with complex scaffolds.

Язык: Английский

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A spectroscopic test suggests that fragment ion structure annotations in MS/MS libraries are frequently incorrect

Communications Chemistry, Год журнала: 2024, Номер 7(1)

Опубликована: Фев. 14, 2024

Abstract Modern untargeted mass spectrometry (MS) analyses quickly detect and resolve thousands of molecular compounds. Although features are readily annotated with a formula in high-resolution small-molecule MS applications, the large majority them remains unidentified terms their full structure. Collision-induced dissociation tandem (CID-MS 2 ) provides diagnostic fingerprint to structure through library search. However, for de novo identifications, one must often rely on silico generated spectra as reference. The ability different algorithms correctly predict thus retrieve correct structures is topic lively debate, instance CASMI contest. Underlying predicted product ion structures, which normally not used identification, but can serve critically assess fragmentation algorithms. Here we evaluate n by comparison established experimentally infrared spectroscopy (IRIS). For set three dozen from five precursor molecules, find that virtually all fragment annotations major libraries (HMDB, METLIN, mzCloud) incorrect caution reader against use annotation MS/MS ions.

Язык: Английский

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Mass Spectral Library for DNA Adductomics

Chemical Research in Toxicology, Год журнала: 2024, Номер 37(2), С. 302 - 310

Опубликована: Янв. 17, 2024

Endogenous electrophiles, ionizing and non-ionizing radiation, hazardous chemicals present in the environment diet can damage DNA by forming covalent adducts. adducts form critical cancer driver genes and, if not repaired, may induce mutations during cell division, potentially leading to onset of cancer. The detection quantification specific are some first steps studying their role carcinogenesis, physiological conditions that lead production, risk assessment exposure genotoxic chemicals. Hundreds different have been reported literature, there is a need establish adduct mass spectral database facilitate previously observed characterize newly discovered We collected synthetic standards from research community, acquired MSn (n = 2, 3) fragmentation spectra using Orbitrap Quadrupole-Time-of-Flight (Q-TOF) MS instrumentation, processed data incorporated it into MassBank North America (MoNA) database, created portal Web site (https://sites.google.com/umn.edu/dnaadductportal) serve as central location for metadata, including downloadable formats. This library should prove be valuable resource adductomics accelerating improving our understanding disease.

Язык: Английский

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Soil metabolomics: Deciphering underground metabolic webs in terrestrial ecosystems

Eco-Environment & Health, Год журнала: 2024, Номер 3(2), С. 227 - 237

Опубликована: Март 21, 2024

Soil metabolomics is an emerging approach for profiling diverse small molecule metabolites, i.e., metabolomes, in the soil. including fatty acids, amino lipids, organic sugars, and volatile compounds, often contain essential nutrients such as nitrogen, phosphorus, sulfur are directly linked to soil biogeochemical cycles driven by microorganisms. This paper presents overview of methods analyzing metabolites state-of-the-art relation nutrient cycling. We describe important applications studying carbon cycling sequestration, response pools changing environmental conditions. includes using provide new insights into close relationships between microbiome metabolome, well responses metabolome plant stresses contamination. also highlight advantage study elements suggest that future research needs better understand factors driving function health.

Язык: Английский

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Reincarnation of libraries via metaverse: A pathway for a sustainable knowledge system in the digital age

Business Information Review, Год журнала: 2023, Номер 40(4), С. 191 - 197

Опубликована: Окт. 19, 2023

The evolution of metaverse libraries offers a transformative pathway for redefining knowledge systems in the digital age. This study delves into seamless integration enduring library principles with expansive capabilities metaverse, envisioning harmonious coexistence that preserves traditional values while propelling dissemination, inclusivity, and collaboration to new heights. Real-world case studies provide valuable insights successful implementations offer lessons future endeavors. By seamlessly merging attributes immersive experiences, can tailored learning journeys, foster global collaboration, ensure secure content distribution. However, landscape is not without challenges, such as privacy concerns, literacy gaps, imperative all which require thoughtful interdisciplinary collaboration. underscores significance preserving essence physical embracing potential metaverse. Through adept navigation these complexities, have capacity revolutionize education, nurture equitable access dynamic interconnected landscape.

Язык: Английский

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