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.
Study ID | ST003065 |
Study Title | Investigative needle core biopsies for multi-omics in Glioblastoma |
Study 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 |
sstopka@bwh.harvard.edu | |
Phone | 617-525-9746 |
Submit Date | 2024-02-01 |
Raw Data Available | Yes |
Raw Data File Type(s) | imzML |
Analysis Type Detail | MALDI |
Release Date | 2025-02-03 |
Release Version | 1 |
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 |
---|---|---|
SA331991 | btc_pilot_tissue-total ion count | btc_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 |