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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Deep Learning-Enabled MS/MS Spectrum Prediction Facilitates Automated Identification Of Novel Psychoactive Substances

The market for illicit drugs has been reshaped by the emergence of more than 1100 new psychoactive substances (NPS) over the past decade, posing a major challenge to the forensic and toxicological laboratories tasked with detecting and identifying them. Tandem mass spectrometry (MS/MS) is the primary method used to screen for NPS within seized materials or biological samples. The most contemporary workflows necessitate labor-intensive and expensive MS/MS reference standards, which may not be available for recently emerged NPS on the illicit market. Here, we present NPS-MS, a deep learning method capable of accurately predicting the MS/MS spectra of known and hypothesized NPS from their chemical structures alone. NPS-MS is trained by transfer learning from a generic MS/MS prediction model on a large data set of MS/MS spectra. We show that this approach enables a more accurate identification of NPS from experimentally acquired MS/MS spectra than any existing method. We demonstrate the application of NPS-MS to identify a novel derivative of phencyclidine (PCP) within an unknown powder seized in Denmark without the use of any reference standards. We anticipate that NPS-MS will allow forensic laboratories to identify more rapidly both known and newly emerging NPS. NPS-MS is available as a web server at https://nps-ms.ca/, which provides MS/MS spectra prediction capabilities for given NPS compounds. Additionally, it offers MS/MS spectra identification against a vast database comprising approximately 8.7 million predicted NPS compounds from DarkNPS and 24.5 million predicted ESI-QToF-MS/MS spectra for these compounds.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Boron isotopic analysis in bulk silicate materials using the Neoma MS/MS MC-ICP-MS

Boron (B) isotopes are a valuable tracer with applications ranging from geological, environmental, and nuclear studies because B isotopic fractionation is highly sensitive to chemical processes yielding distinct isotopic trends in natural and anthropogenic systems. Despite this wide applicability, there remain relatively few measurements on well-described reference materials and in some cases, poor agreement between various methods. We report a method for boron isotope ratio measurement in solution on the Neoma MS/MS MC-ICP-MS specifically targeting bulk silicates. We evaluate the performance of the method and instrument as it relates to the measurement of the absolute boron isotope ratio ( 10 B/ 11 B). The results indicate that the method produces data in agreement with literature values and that the sample–standard bracketing technique is appropriate for the Neoma MS/MS MC-ICP-MS which has been in use for decades on previous generation instruments. Careful tuning of the MS/MS lenses is required to obtain precision comparable to non MS/MS equipped MC-ICP-MS. With careful tuning, internal and external precisions of ∼0.3‰ were achieved. However, when the MS/MS is not properly tuned external precisions exceed 3‰. Nevertheless, our results for IAEA B-6, BCR-2, BHVO-2 and W-2a reference materials overlap the 1σ range of previously reported 10 B/ 11 B. Data are reported for total boron quantities down to a few tens of nanograms. Our procedure yielded blanks as low as 3 ng but up to 29 ng, making blank corrections important for small samples sizes in the few 10s of nanogram range. We report B isotope ratios for AGV-2G, SL-1G, GSC-2G, GSD-2G, GSE-2G, RLS-132, RLS-140, NKT-1G, and T1-G glass reference materials that have not been previously reported in the literature.

Scott, Sean R. [Pacific Northwest National Laborat↗
DOE OSTI2022

Augmentation of MS/MS Libraries with Spectral Interpolation for Improved Identification

Tandem mass spectrometry (MS/MS) is a primary tool for identification of small molecules and metabolites where resultant spectra are most commonly identified by matching them with spectra in MS/MS reference libraries. The high degree of variability in MS/MS spectrum acquisition techniques and parameters creates a significant challenge for building standardized reference libraries. Here we present a method to improve the usefulness of existing MS/MS libraries by augmenting available experimental spectra datasets with statistically interpolated spectra at unreported collision energies. We find that highly accurate spectral approximations can be interpolated from as few as three experimental spectra and that the interpolated spectra will be consistent with true spectra gathered from the same instrument as the experimental spectra. Supplementing existing spectral databases with interpolated spectra yields consistent improvements to identification accuracy on a range of instruments and precursor types. Applying this method yields significant improvements (~10% more spectra correctly identified) on large datasets (2,000 - 10,000 spectra), indicating this is a quick yet adept tool for improving spectral matching in situations where available reference libraries are not yet sufficient. We also find improvements of matching spectra across instrument types (between an Agilent Q-TOF and an Orbitrap Elite), at high collision energies (50 - 90 eV), and with smaller datasets available through MassBank.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Development of a Universal Second-Tier Newborn Screening LC–MS/MS Method for Amino Acids, Lysophosphatidylcholines, and Organic Acids

First-tier MS-based newborn screening by flow injection analysis can have high presumptive positive rates, often due to isomeric/isobaric compounds or poor biomarker specificity. These presumptive positive samples can be analyzed by second-tier screening assays employing separations such as liquid chromatography–mass spectrometry (LC–MS/MS), which increases test specificity and drastically reduces false positive referrals. The ability to screen for multiple disorders in a single multiplexed test simplifies workflows and maximizes public health laboratories’ resources. In this study, we developed and validated a highly multiplexed second-tier method for dried blood spots using a hydrophilic interaction liquid chromatography (HILIC) column coupled to an MS/MS system. The LC–MS/MS method was capable of simultaneously detecting second-tier biomarkers for maple syrup urine disease, homocystinuria, methylmalonic acidemia, propionic acidemia, glutaric acidemia type 1, glutaric acidemia type 2, guanidinoacetate methyltransferase deficiency, short-chain acyl-CoA dehydrogenase deficiency, adrenoleukodystrophy, and Pompe disease.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Advancing the Prediction of MS/MS Spectra Using Machine Learning

Tandem mass spectrometry (MS/MS) is an important tool for the identification of small molecules and metabolites where resultant spectra are most commonly identified by matching them with spectra in MS/MS reference libraries. While popular, this strategy is limited by the contents of existing reference libraries. In response to this limitation, various methods are being developed for the in silico generation of spectra to augment existing libraries. Recently, machine learning and deep learning techniques have been applied to predict spectra with greater speed and accuracy. Here, in this work, we investigate the challenges these algorithms face in achieving fast and accurate predictions on a wide range of small molecules. The challenges are often amplified by the use of generic machine learning benchmarking tactics, which lead to misleading accuracy scores. Curating data sets, only predicting spectra for sufficiently high collision energies, and working more closely with experimental mass spectrometrists are recommended strategies to improve overall prediction accuracy in this nuanced field.

47 OTHER INSTRUMENTATION↗
DOE OSTI2025

Lithium isotope analysis on the Neoma MS/MS MC-ICP-MS

Accurate and precise lithium isotopic composition measurements are achieved on the Neoma MS/MS after careful tuning of the prefilter lenses to allow both Li ion beams to pass through unimpeded.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2021

CFM-ID 4.0: More Accurate ESI MS/MS Spectral Prediction and Compound Identification

In the field of metabolomics, mass spectrometry (MS) is the method most commonly used for identifying and annotating metabolites. As this typically involves matching a given MS spectrum against an experimentally acquired reference spectral library, this approach is limited by the coverage and size of such libraries (which typically number in the thousands). These experimental libraries can be greatly extended by predicting the MS spectra of known chemical structures (which number in the millions) to create computational reference spectral libraries. To facilitate the generation of predicted spectral reference libraries we developed CFM-ID, a computer program that can accurately predict ESI-MS/MS spectrum for a given compound structure. CFM-ID is one of the best-performing methods for compound-to-mass-spectrum prediction, and also one of the top tools for in silico mass-spectrum-to-compound identification. This work improves CFM-ID’s ability to predict ESI-MS/MS spectra from compounds by: (1) learning parameters from features based on the molecular topology, (2) adding a new approach to ring cleavage that models such cleavage as a sequence of simple chemical bond dissociations and (3) expanding its hand-written rule-based predictor to cover more chemical classes, including acylcarnitines, acylcholines, flavonols, flavones, flavanones, and flavonoid glycosides. We demonstrate that this new version of CFM-ID (version 4.0) is significantly more accurate than previous CFM-ID versions, in terms of both EI-MS/MS spectral prediction and compound identification. CFM-ID 4.0 is available at http://cfmid4.wishartlab.com/ as a webservice and docker images can be downloaded at https://hub.docker.com/r/wishartlab/cfmid

Wang, Fei↗
NASA NTRS1973

Acoustic processing method for MS/MS experiments

Acoustical methods in which intense sound beams can be used to control the position of objects are considered. The position control arises from the radiation force experienced when a body is placed in a sound field. A description of the special properties of intense sound fields useful for position control is followed by a discussion of the more obvious methods of position, namely the use of multiple sound beams. A new type of acoustic position control device is reported that has advantages of simplicity and reliability and utilizes only a single sound beam. Finally a description is given of an experimental single beam levitator, and the results obtained in a number of key levitation experiments.

Whymark, R. R.↗
DOE OSTI2022

CFM-ID 4.0 – a web server for accurate MS-based metabolite identification

The CFM-ID 4.0 web server (https://cfmid.wishartlab.com) is an online tool for predicting, annotating and interpreting tandem mass (MS/MS) spectra of small molecules. It is specifically designed to assist researchers pursuing studies in metabolomics, exposomics and analytical chemistry. More specifically, CFM-ID 4.0 supports the: 1) prediction of electrospray ionization quadrupole time-of-flight tandem mass spectra (ESI-QTOF-MS/MS) for small molecules over multiple collision energies (10 eV, 20 eV, and 40 eV); 2) annotation of ESI-QTOF-MS/MS spectra given the structure of the compound; and 3) identification of a small molecule that generated a given ESI-QTOF-MS/MS spectrum at one or more collision energies. The CFM-ID 4.0 web server makes use of a substantially improved MS fragmentation algorithm, a much larger database of experimental and in silico predicted MS/MS spectra and improved scoring methods to offer more accurate MS/MS spectral prediction and MS/MS-based compound identification. Compared to earlier versions of CFM-ID, this new version has an MS/MS spectral prediction performance that is ~22% better and a compound identification accuracy that is ~35% better on a standard (CASMI 2016) testing dataset. CFM-ID 4.0 also features a neutral loss function that allows users to identify similar or substituent compounds where no match can be found using CFM-ID’s regular MS/MS-to-compound identification utility. Finally, the CFM-ID 4.0 web server now offers a much more refined user interface that is easier to use, supports molecular formula identification (from MS/MS data), provides more interactively viewable data (including proposed fragment ion structures) and displays MS mirror plots for comparing predicted with observed MS/MS spectra. These improvements should make CFM-ID 4.0 much more useful to the community and should make small molecule identification much easier, faster, and more accurate.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Annotation of DOM metabolomes with an ultrahigh resolution mass spectrometry molecular formula library

Current approaches to analyzing metabolomic data often rely on matching MS/MS fragmentation data to sparse libraries or databases. This approach results in limited identification of features, often with less than 10% of the dataset being annotated. A complementary approach is to assign molecular formula to features based on accurate mass measurements, but the platforms commonly used for metabolomics do not have the needed accuracy or resolving power to do this robustly, particularly for larger molecules. Using our newly modified analysis tool, CoreMS, we generated a library of molecular formula from pooled samples analyzed with LC-21T FT-ICR MS. This library successfully annotated approximately 53.2% of features identified from the exometabolome of marine diatom Phaeodactylum tricornutum – a nearly ten-fold increase over the 5.9% annotation rate achieved using a conventional MS/MS library matching approach. Using this FT-ICR MS library approach, we were able to differentiate differences in the exometabolome of P. tricornutum in iron replete and iron limited conditions, with 668 metabolites being differentially expressed (p < 0.05, 2 x intensity difference) under these conditions. The traditional MS/MS fragmentation-based annotation approach only annotated 61 of these metabolites, while our novel pipeline annotated 450 metabolites and revealed 12 metabolites that were significantly more abundant under low iron conditions. Our results demonstrate the utility of ultrahigh resolution mass spectrometry for generating more comprehensive and confident molecular annotations.

21T-FTICR-MS, CoreMS↗
DOE OSTI2023

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

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

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Comparability of Liquid Chromatography Tandem Mass Spectrometry Analysis of Dissolved Organic Matter across Laboratories

Non-targeted liquid chromatography tandem highresolution mass spectrometry (LC−MS/MS) is increasingly applied for the structure-resolved chemical analysis of dissolved organic matter (DOM). With new developments in MS instrumentation and analysis software, the approach has gained substantial momentum over the past decade. However, achieving high-quality analytical data that is reproducible and comparable across laboratories can be a bottleneck in non-targeted metabolomics and organic matter chemical analysis, especially for data reuse in repository-scale analyses. Understanding the capabilities as well as challenges of comparing LC−MS/MS data from different laboratories is necessary for inferring global trends from public data sets. To illuminate instrumentation factors that drive differences and variability, we used a standardized data analysis pipeline, including classical (CMN) and featurebased molecular networking (FBMN), to analyze data from a ring trial by 24 laboratories on identical sample sets of algal and DOM extracts that were mixed in predefined concentrations and spiked with standards. Our results showed that data sets from similar mass spectrometer types with unified instrument parameters were qualitatively comparable, resolving the same general trends and shared mass spectral features. Interlaboratory comparability was best for high-intensity features, while low-intensity features showed greater detection variability. Our analysis also highlights challenges when comparing data from instruments with different acquisition rates or operating with less standardized methods. Lastly, we provide recommendations for data integration, public data sharing, standardization, and best practices for standardized LC−MS/MS data acquisition, which will be critical for long-term time series and intercomparability of DOM chemical analyses.

DOM↗
DOE OSTI2021

Grazer-induced changes in molecular signatures of cyanobacteria

Algal biomass production is an emerging renewable source of fuels, nutrients, manufacturing materials, and pharmaceuticals. Industrial-scale production is predominantly performed in open raceway ponds that are inexpensive to build, operate, and maintain compared to closed bioreactors. However, these open pond systems suffer from increased opportunities for biological contamination from predators, pathogens, and competitors, which result in reduced biomass quality and yields and often the complete destruction of the crop over a short period of time. Early detection of contaminants is a necessary step of integrated pest management for triggering and informing interventions to prevent crop losses. To develop a sensitive method of detection utilizing mass spectrometry (MS), we used three methods – imaging mass spectrometry (imaging MS), liquid chromatography MS/MS (LC-MS/MS) combined with molecular networking, and gas chromatography MS/MS (GC–MS/MS) – to observe and identify molecular signatures from a model predator-prey system of the heterolobosean amoeba HGG1 preying on the filamentous cyanobacterium Anabaena sp. PCC 7120. Imaging MS enabled the association of molecules with the crop, the predator, or the activity of protozoan grazing, while LC-MS/MS-based molecular networking identified a subset of the grazing-specific signals as the chlorophyll breakdown products pyropheophytin, pheophorbide A, and pyropheophorbide. Application of MS techniques to other amoebacyanobacterial predator-prey pairs allowed categorization of grazing signatures as universal or specific to the species of prey, predator, or the prey-predator pairing, indicating that MS-based techniques can distinguish crops from competitors and potentially identify predators. Finally, GCMS/MS was shown to be capable of monitoring novel volatile organic compounds (VOCs), including those predicted to be released through chlorophyll breakdown, in the headspace over algal cultures under predation. Furthermore, these results demonstrate that the combination of multiple MS technologies creates a predictive framework to identify and catalog relevant molecular signatures for informing crop protection strategies.

09 BIOMASS FUELS↗
DOE OSTI2024

Identification of Unique Fragmentation Patterns of Fentanyl Analog Protomers Using Structures for Lossless Ion Manipulations Ion Mobility-Orbitrap Mass Spectrometry

The opioid crisis in the United States is being fueled by the rapid emergence of new fentanyl analogs and precursors that can elude traditional library-based screening methods, which require data from known reference compounds. Since reference compounds are unavailable for new fentanyl analogs, we examined if fentanyls (fentanyl + fentanyl analogs) could be identified in a reference-free manner using a combination of electrospray ionization (ESI), high-resolution ion mobility (IM) spectrometry, high-resolution mass spectrometry (MS), and higher-energy collision-induced dissociation (MS/MS). We analyzed a mixture containing nine fentanyls and W-15 (a structurally similar molecule) and found that the protonated forms of all fentanyls uniquely exhibited two baseline separated IM distributions that produced different MS/MS patterns. Upon fragmentation, both IM distributions of all fentanyls produced two high intensity fragments resulting from amine site cleavages. The higher mobility distributions of all fentanyls also produced several low intensity fragments, but surprisingly, these same fragments exhibited much greater intensities in the lower mobility distributions. This observation demonstrates that many fragments of fentanyls predominantly originate from one of two different gas-phase structures (suggestive of protomers). Furthermore, increasing the water concentration in the ESI solution increased the intensity of the lower mobility distribution relative to the higher mobility distribution, which further supports that fentanyls exist as two gas-phase protomers. In conclusion, our new observations on the IM and MS/MS properties of fentanyls can be exploited to positively identify them as fentanyls without requiring reference libraries and will hopefully assist first responders and law enforcement in combating new and emerging fentanyls.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Gas‐Phase Ion‐Molecule Interactions in a Collision Reaction Cell with ICP‐MS / MS : Investigations with CO 2 as the Reaction Gas

Carbon dioxide (CO 2 ) was used as a reaction gas to investigate the gas‐phase ion‐molecule interactions using the Agilent 8900 ICP‐MS/MS. A solution containing forty‐five elements representative of the periodic table was used to supply the ions to react with CO 2 in the collision/reaction cell (CRC). The only significant product ions formed were monoxides. The general reactivity was shown to be consistent with density functional theory (DFT)‐predicted reaction enthalpies, such that all predicted exothermic reactions produced product ions at levels of at least 1% of the unreacted ion. Most endothermic reactions observed had sufficient kinetic energy in excess of the reaction enthalpies. Our results suggest that reaction enthalpy is a reasonable predictor of reactivity with CO 2 on the timescales of the interactions in non‐thermal ICP‐MS/MS systems. The ease and rapidity of data collection with the ICP‐MS/MS and DFT calculations using the NWChem suite has value given the scarcity of thermochemical data of CO 2 reactions in the literature. These studies are especially useful for the identification of targeted reaction chemistries to be leveraged for analytical method development, such as for the inline separation of isobaric interferences from analytes of interest.

36 MATERIALS SCIENCE↗