Summary of Study ST003065

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001911. The data can be accessed directly via it's Project DOI: 10.21228/M8Q148 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003065
Study TitleInvestigative needle core biopsies for multi-omics in Glioblastoma
Study SummaryGlioblastoma (GBM) is a primary brain cancer with an abysmal prognosis and few effective therapies. The ability to investigate the tumor microenvironment before and during treatment would greatly enhance both our understanding of disease response and progression, as well as the delivery and impact of therapeutics. Stereotactic biopsies are a routine surgical procedure performed primarily for diagnostic histopathologic purposes. The role of investigative biopsies – tissue sampling for the purpose of understanding tumor microenvironmental responses to treatment using integrated multi-modal molecular analyses (‘Multi-omics”) has yet to be defined. Here we adapt stereotactic needle core biopsy tissue for highly resolved multi-omics analysis methods including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics. Biopsy tissue was obtained from a single patient with recurrent GBM during one procedure. In a second patient, we analyzed multi-regional core biopsies to decipher spatial and genomic variance. Finally in a separate cohort of patients we investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft models. Dataset integration across modalities showed good correspondence between spatial modalities and highlighted immune cell associated metabolic pathways and poor correlation between RNA expression and the tumor MHC Class I immunopeptidome. In conclusion, stereotactic needle biopsy cores are of sufficient quality for the purposes of investigative biopsy and can generate multi-omics data, providing data rich insight into a patient’s disease process and tumor immune microenvironment and could be of potential value in evaluating treatment responses.
Institute
Brigham and Women's Hospital
DepartmentDepartment of Neurosurgery
LaboratoryNathalie Y.R. Agar
Last NameStopka
First NameSylwia
Address60 Fenwood Rd
Emailsstopka@bwh.harvard.edu
Phone617-525-9746
Submit Date2024-02-01
Raw Data AvailableYes
Raw Data File Type(s)imzML
Analysis Type DetailMALDI
Release Date2025-02-03
Release Version1
Sylwia Stopka Sylwia Stopka
https://dx.doi.org/10.21228/M8Q148
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR001911
Project DOI:doi: 10.21228/M8Q148
Project Title:Investigative needle core biopsies for multi-omics in Glioblastoma
Project Type:Single Cell Spatial Analysis Reveals the Topology of Immunomodulatory Purinergic Signaling in Glioblastoma
Project Summary:Glioblastoma (GBM) is a primary brain cancer with an abysmal prognosis and few effective therapies. The ability to investigate the tumor microenvironment before and during treatment would greatly enhance both our understanding of disease response and progression, as well as the delivery and impact of therapeutics. Stereotactic biopsies are a routine surgical procedure performed primarily for diagnostic histopathologic purposes. The role of investigative biopsies – tissue sampling for the purpose of understanding tumor microenvironmental responses to treatment using integrated multi-modal molecular analyses (‘Multi-omics”) has yet to be defined. Here we adapt stereotactic needle core biopsy tissue for highly resolved multi-omics analysis methods including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics. Biopsy tissue was obtained from a single patient with recurrent GBM during one procedure. In a second patient, we analyzed multi-regional core biopsies to decipher spatial and genomic variance. Finally in a separate cohort of patients we investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft models. Dataset integration across modalities showed good correspondence between spatial modalities and highlighted immune cell associated metabolic pathways and poor correlation between RNA expression and the tumor MHC Class I immunopeptidome. In conclusion, stereotactic needle biopsy cores are of sufficient quality for the purposes of investigative biopsy and can generate multi-omics data, providing data rich insight into a patient’s disease process and tumor immune microenvironment and could be of potential value in evaluating treatment responses.
Institute:Brigham and Women's Hospital
Department:Department of Neurosurgery
Laboratory:Nathalie Y.R. Agar
Last Name:Stopka
First Name:Sylwia
Address:60 Fenwood Rd,
Email:sstopka@bwh.harvard.edu
Phone:617-525-9746

Subject:

Subject ID:SU003180
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Mammals

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id sample_id
SA331991btc_pilot_tissue-total ion countbtc_pilot_tissue-total ion count
Showing results 1 to 1 of 1

Collection:

Collection ID:CO003173
Collection Summary:Biopsy Core Four underwent a preservation process, being rapidly frozen on dry ice. For MALDI MSI the core was then cryo-sectioned into 10 µm-thick slices.
Sample Type:Brain

Treatment:

Treatment ID:TR003189
Treatment Summary:N/A

Sample Preparation:

Sampleprep ID:SP003186
Sampleprep Summary:Biopsy Core Four underwent a preservation process, being rapidly frozen on dry ice. For MALDI MSI the core was then cryo-sectioned into 10 µm-thick slices. These slices were subsequently thaw-mounted onto an indium tin oxide (ITO) slide. Serial sections were prepared for microscopy staining. For the mass spectrometry analysis, we utilized a 1,5-diaminonaphthalene hydrochloride MALDI matrix, with 15N glutamate spiked in as an internal standard. The matrix was prepared at a concentration of 4.3 mg/mL in a mixture of 4.5 parts HPLC grade water, 5 parts ethanol, and 0.5 parts 1 M HCl (v/v/v). A TM-sprayer from HTX Imaging was used to spray the matrix, with the following parameters: a flow rate of 0.09 mL/min, spray nozzle velocity of 1200 mm/min, spray nozzle temperature of 75 °C, nitrogen gas pressure of 10 psi, track spacing of 2 mm, and a four-pass spray. The mass spectrometry analysis was carried out using a 15 Tesla SolariX XR FT-ICR MS (Bruker Daltonics, Billerica, MA). The instrument was set to negative ion mode, and the mass range scanned was from m/z 46.07 to 3000, with a sampling step size of 30 µm. Each sampling point consisted of 200 laser shots at a laser power of 21% (arbitrary scale), with a laser repetition rate of 1,000 Hz. We employed the Continuous Accumulation of Selected Ions (CASI) mode, setting Q1 to m/z 150 with an isolation window of 200. The mass range was calibrated using a tune mix solution from Agilent Technologies with the electrospray source. Additionally, the internal standard 15N glutamate was used for on-line calibration during the acquisition. For data analysis, SCiLS Lab software (version 2023c Pro, Bruker Daltonics, Billerica, MA) was used to view and process ion images and mass spectra. The dataset was normalized to the total ion current (TIC), and peaks were annotated using Metaboscape (2021b,Bruker Daltonics, Billerica, MA)). Metabolites were putatively annotated based on an accurate mass with a Δppm < 0.5 and MSMS measurements. MetaboanalystR (85) was used to perform pathway enrichment analysis at every pixel. The resulting enrichment ratios were displayed spatially with an in-house R script. Metabolite differential expression was tested with a t-test and FDR correction.

Combined analysis:

Analysis ID AN005021
Analysis type MS
Chromatography type None (Direct infusion)
Chromatography system none
Column none
MS Type MALDI
MS instrument type FT-ICR
MS instrument name Bruker Solarix FT-ICR-MS
Ion Mode NEGATIVE
Units Total Ion Count

Chromatography:

Chromatography ID:CH003793
Instrument Name:none
Column Name:none
Column Temperature:none
Flow Gradient:none
Flow Rate:none
Solvent A:none
Solvent B:none
Chromatography Type:None (Direct infusion)

MS:

MS ID:MS004760
Analysis ID:AN005021
Instrument Name:Bruker Solarix FT-ICR-MS
Instrument Type:FT-ICR
MS Type:MALDI
MS Comments:Bruker software
Ion Mode:NEGATIVE
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