Inline cartridge extraction for rapid brain tumor tissue identification by molecular profiling

Pekov, Stanislav I.; Eliferov, Vasiliy A.; Sorokin, Anatoly; Shurkhay, Vsevolod; Zhvansky, Evgeny; Vorobyev, A. S.; Потапов, А. А.; Nikolaev, Eugene; Popov, Igor

doi:10.1038/s41598-019-55597-7

Cited by 19 publications

(22 citation statements)

References 37 publications

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“…The experiments were performed on a Thermo LTQ Orbitrap XL (high and low resolution, laboratory conditions) and Thermo LTQ XL (only low resolution, clinical conditions) instruments. Mass spectrometric data were obtained using the inline cartridge extraction (ICE) 26 followed by electrospray ionization in both positive and negative ion modes. Spectra from Thermo LTQ Orbitrap XL were measured with two resolutions: 24 000 at m/z = 744 (high resolution using Orbitrap analyzer) and 2000 at m/z = 744 (low resolution using LTQ analyzer).…”

Section: Methodsmentioning

confidence: 99%

Assessment of variation of inline cartridge extraction mass spectra

et al. 2020

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Recently, mass-spectrometry methods show its utility in tumor boundary location.The effect of differences between research and clinical protocols such as low-and high-resolution measurements and sample storage have to be understood and taken into account to transfer methods from bench to bedside. In this study, we demonstrate a simple way to compare mass spectra obtained by different experimental protocols, assess its quality, and check for the presence of outliers and batch effect in the dataset. We compare the mass spectra of both fresh and frozen-thawed astrocytic brain tumor samples obtained with the inline cartridge extraction prior to electrospray ionization. Our results reveal the importance of both positive and negative ion mode mass spectrometry for getting reliable information about sample diversity. We show that positive mode highlights the difference between protocols of mass spectra measurement, such as fresh and frozen-thawed samples, whereas negative mode better characterizes the histological difference between samples. We also show how the use of similarity spectrum matrix helps to identify the proper choice of the measurement parameters, so data collection would be kept reliable, and analysis would be correct and meaningful. K E Y W O R D Sbrain tumor, data conversion, inline cartridge extraction, low-and high-resolution comparison, spectra stability and reproducibility | INTRODUCTIONFast tissue profiling methods for mass spectrometers allowed developing methods of rapid analysis of biological substances. [1][2][3][4][5][6][7] There are a lot of attempts to incorporate mass spectrometry into the clinical routine for surgery assistance purposes. [8][9][10][11][12] Mass spectra of complex mixtures of biological molecules, even those whose mass is up to 1000 Da, is still rather a difficult task, because of the enormous diversity of molecules contained in biological tissues. 13,14 Despite the common practice of LC-MS/MS to be used as an instrument for accurate identification of complex mixture components, it could not be used as a routine technique for rapid analyses. 15 Therefore, rapid analyses

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Section: Methodsmentioning

confidence: 99%

Assessment of variation of inline cartridge extraction mass spectra

et al. 2020

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“…Mass spectra were processed in a similar way to previously described [23][24][25][26][27][28][29][30] . So, mass spectra were converted to vectors with 1m/z binning width and were normalized to total ion current.…”

Section: Discussionmentioning

confidence: 99%

“…The study used a Thermo LTQ Orbitrap XL high-resolution mass spectrometer, which allows measurements in both highand low-resolution spectra. For mass spectrometric profiling of the samples, extraction using an integrated cartridge (ICE) 28 was used, followed by electrospray ionization. Mass spectra were measured according to a previously developed protocol 29 .…”

Section: Signal Acquisitionmentioning

confidence: 99%

Analysis of ion currents in mass spectrometric profiles using glioblastoma tissue

et al. 2021

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Background: The development of direct ambient ionization methods makes way for fast mass-spectrometry profiling of biological samples, which has great potential in medicine. Those methods, unlike traditional mass spectrometric analysis with chromatographic separation, are not able to take into account inter-ion interaction, ion suppression, and matrix effect due to the absence of chromatographic separation of the mixture components. So dynamics of ion current during direct ambient ionization mass-spectra is governed by the component micro-extraction and electrospray ionization influenced by the geometry of the sample, its position, and internal heterogeneity. Despite the progress in mass-spectrometry of biological samples, not much is known about the influence of sample type and structure on its molecular profile peculiarities. Methods: In this work, we propose to use analysis of the correlation between individual ion currents for a better understanding of ion current variability sources and grouping ions of high biological importance. Several fragments of glioblastoma tissue from a single patient are used for these purposes. Results: Ion currents have different dynamics considering different ions in different fragments. The correlation of two selected ion currents could be positive or negative for single fragment measurement. Correlations have persistent or alternating signs in different fragments for two selected ions. The spread of correlations of each pair of ion currents is calculated for evaluation of the signs’ stability. Conclusions: We were able to group ions according to the primary reason for their variabilities such as micro-extraction, mass-spectrometry measurement, or specimens' properties. Such grouping would allow the development of more reliable and reproducible methods of mass-spectrometry data analysis and improve the accuracy of results of its application in medicine.

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“…Spectra were measured in low resolution under clinical conditions with Thermo LTQ XL. Inline cartridge extraction 23 ) followed by electrospray ionization was used for mass spectrometric profiling of samples, which proceeds microextraction of substances from the sample in the solvent flow, while the sample is held on the glass microfiber filter. Spectra from Thermo LTQ XL were measured in both positive and negative ion modes with resolutions 2000 at m / z 744.…”

Section: Methodsmentioning

confidence: 99%

“…We have used astrocytoma and glioblastoma MS data obtained with inline cartridge extraction 23 ) as a dataset. Each sample of the tumor is characterized by a series of consecutively measured mass spectra (scans) during the extraction.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Dimensionality Reduction Methods in Mass Spectra of Astrocytoma and Glioblastoma Tissues

et al. 2021

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Recently developed methods of ambient ionization allow the collection of mass spectrometric datasets for biological and medical applications at an unprecedented pace. One of the areas that could employ such analysis is neurosurgery. The fast in situ identification of dissected tissues could assist the neurosurgery procedure. In this paper tumor tissues of astrocytoma and glioblastoma are compared. The vast majority of the data representation methods are hard to use, as the number of features is high and the amount of samples is limited. Furthermore, the ratio of features and samples number restricts the use of many machine learning methods. The number of features could be reduced through feature selection algorithms or dimensionality reduction methods. Different algorithms of dimensionality reduction are considered along with the traditional noise thresholding for the mass spectra. From our analysis, the Isomap algorithm appears to be the most effective dimensionality reduction algorithm for negative mode, whereas the positive mode could be processed with a simple noise reduction by a threshold. Also, negative and positive mode correspond to different sample properties: negative mode is responsible for the inner variability and the details of the sample, whereas positive mode describes measurement in general.

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Inline cartridge extraction for rapid brain tumor tissue identification by molecular profiling

Cited by 19 publications

References 37 publications

Assessment of variation of inline cartridge extraction mass spectra

Assessment of variation of inline cartridge extraction mass spectra

Analysis of ion currents in mass spectrometric profiles using glioblastoma tissue

Comparison of Dimensionality Reduction Methods in Mass Spectra of Astrocytoma and Glioblastoma Tissues

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