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New methods to identify high peak density artifacts in Fourier transform mass spectra and to mitigate their effects on high-throughput metabolomic data analysis.

ABSTRACT: INTRODUCTION:Direct injection Fourier-transform mass spectrometry (FT-MS) allows for the high-throughput and high-resolution detection of thousands of metabolite-associated isotopologues. However, spectral artifacts can generate large numbers of spectral features (peaks) that do not correspond to known compounds. Misassignment of these artifactual features creates interpretive errors and limits our ability to discern the role of representative features within living systems. OBJECTIVES:Our goal is to develop rigorous methods that identify and handle spectral artifacts within the context of high-throughput FT-MS-based metabolomics studies. RESULTS:We observed three types of artifacts unique to FT-MS that we named high peak density (HPD) sites: fuzzy sites, ringing and partial ringing. While ringing artifacts are well-known, fuzzy sites and partial ringing have not been previously well-characterized in the literature. We developed new computational methods based on comparisons of peak density within a spectrum to identify regions of spectra with fuzzy sites. We used these methods to identify and eliminate fuzzy site artifacts in an example dataset of paired cancer and non-cancer lung tissue samples and evaluated the impact of these artifacts on classification accuracy and robustness. CONCLUSION:Our methods robustly identified consistent fuzzy site artifacts in our FT-MS metabolomics spectral data. Without artifact identification and removal, 91.4% classification accuracy was achieved on an example lung cancer dataset; however, these classifiers rely heavily on artifactual features present in fuzzy sites. Proper removal of fuzzy site artifacts produces a more robust classifier based on non-artifactual features, with slightly improved accuracy of 92.4% in our example analysis.

SUBMITTER: Mitchell JM

PROVIDER: S-EPMC6153687 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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New methods to identify high peak density artifacts in Fourier transform mass spectra and to mitigate their effects on high-throughput metabolomic data analysis.

Mitchell Joshua M JM Flight Robert M RM Wang Qing Jun QJ Higashi Richard M RM Fan Teresa W-M TW Lane Andrew N AN Moseley Hunter N B HNB

Metabolomics : Official journal of the Metabolomic Society 20180917 10

<h4>Introduction</h4>Direct injection Fourier-transform mass spectrometry (FT-MS) allows for the high-throughput and high-resolution detection of thousands of metabolite-associated isotopologues. However, spectral artifacts can generate large numbers of spectral features (peaks) that do not correspond to known compounds. Misassignment of these artifactual features creates interpretive errors and limits our ability to discern the role of representative features within living systems.<h4>Objective ...[more]

PMID: 30830442

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Project description:BACKGROUND:Infrared spectral analysis of milk is cheap, fast, and accurate. Infrared light interacts with chemical bonds present inside the milk, which means that Fourier transform infrared milk spectra are a reflection of the chemical composition of milk. Heritability of Fourier transform infrared milk spectra has been analysed previously. Further genetic analysis of Fourier transform infrared milk spectra could give us a better insight in the genes underlying milk composition. Breed influences milk composition, yet not much is known about the effect of breed on Fourier transform infrared milk spectra. Improved understanding of the effect of breed on Fourier transform infrared milk spectra could enhance efficient application of Fourier transform infrared milk spectra. The aim of this study is to perform a genome wide association study on a selection of wavenumbers for Danish Holstein and Danish Jersey. This will improve our understanding of the genetics underlying milk composition in these two dairy cattle breeds. RESULTS:For each breed separately, fifteen wavenumbers were analysed. Overall, more quantitative trait loci were observed for Danish Jersey compared to Danish Holstein. For both breeds, the majority of the wavenumbers was most strongly associated to a genomic region on BTA 14 harbouring DGAT1. Furthermore, for both breeds most quantitative trait loci were observed for wavenumbers that interact with the chemical bond C-O. For Danish Jersey, wavenumbers that interact with C-H were associated to genes that are involved in fatty acid synthesis, such as AGPAT3, AGPAT6, PPARGC1A, SREBF1, and FADS1. For wavenumbers which interact with -OH, associations were observed to genomic regions that have been linked to alpha-lactalbumin. CONCLUSIONS:The current study identified many quantitative trait loci that underlie Fourier transform infrared milk spectra, and thus milk composition. Differences were observed between groups of wavenumbers that interact with different chemical bonds. Both overlapping and different QTL were observed for Danish Holstein and Danish Jersey.

Project description:Janus kinase (JAK) deregulation of the JAK/signal transducers and activators of transcription pathway leads to myelofibrosis that can be treated by JAK inhibitors including Ruxolitinib and Tofacitinib. Even though both inhibitors are effective against myelofibrosis, each of them has a different mode of action in the cells. Ruxolitinib is an inhibitor for selective JAK1/2, and Tofacitinib is an inhibitor for JAK3. This study evaluated the chemical fingerprints of TF-1 cells after JAK inhibitor treatments by the synchrotron Fourier transform infrared microspectroscopy (S-FTIR) spectrum. Tofacitinib and Ruxolitinib treatments in TF-1 cells were applied with a chemical fingerprint approach in S-FTIR spectroscopy and in vitro cytotoxicity in a cell-based assay. Principal component analysis or PCA was utilized to classify three cell treatments with three biochemical alteration absorbances of lipid vibration by the C-H stretching, protein amide I that appeared from the C=O stretching, and a P=O phosphodiester bond from nucleic acids. The results showed that the inhibition effect of Ruxolitinib on the TF-1 cell lines was two-fold higher than Tofacitinib. PCA distinguishes untreated and drug-treated cells by detecting cellular biochemical alteration. The loading plots identify that proteins and nucleic acids were the different main components in disparate cell treatments. Tofacitinib was distinct from the others in lipid and nucleic acid. The second derivative spectra of the three molecular components had decreased lipid production and accumulation, changes in secondary structures in proteins, and a high level of RNA overexpression in cell treatment. The JAK inhibitors caused different spectroscopic biomarkers of the modifications of secondary protein conformation, stimulated cell lipid accumulation, and phosphorylation from untreated cells. The alteration of cellular biochemical components suggests that FTIR is a potential tool to analyze specific patterns of drug cellular responses at the molecular level.

Dataset Information

New methods to identify high peak density artifacts in Fourier transform mass spectra and to mitigate their effects on high-throughput metabolomic data analysis.

Publications

New methods to identify high peak density artifacts in Fourier transform mass spectra and to mitigate their effects on high-throughput metabolomic data analysis.

Similar Datasets

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