Summary of Study ST003102

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 PR001925. The data can be accessed directly via it's Project DOI: 10.21228/M8WM7T This work is supported by NIH grant, U2C- DK119886.

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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 IDST003102
Study TitleCellular adaptation to cancer therapy occurs by progressive state transitions along a resistance continuum
Study SummaryRecent research has shed light on the role of non-genetic plasticity in transient drug tolerance and the acquisition of stable resistance. However, the dynamics of cell state transitions occurring in the adaptation to cancer therapies remain elusive and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell state transitions accompanied by a progressive increase in cell fitness, which we denote the ‘resistance continuum’. This cellular adaptation involves a step-wise assembly of gene expression programs and epigenetically reinforced cell states underpinned by phenotypic plasticity stress adaptation and metabolic reprogramming. Through systematic genetic perturbations, we identify an acquisition of progressive metabolic dependencies, exposing a spectrum of vulnerabilities that can be potentially exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell state transitions.
Institute
NYU Langone Health
Last NameStarvaggi Franca
First NameGustavo
Address430 East 29th Street, NY NY 10016
EmailGustavo.StarvaggiFranca@nyulangone.org
Phone6465015151
Submit Date2024-02-13
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2024-04-02
Release Version1
Gustavo Starvaggi Franca Gustavo Starvaggi Franca
https://dx.doi.org/10.21228/M8WM7T
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN005076
Analysis type MS
Chromatography type HILIC
Chromatography system Ulitmate 3000
Column SeQuant ZIC-pHILIC (150 x 4.6mm,5um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode UNSPECIFIED
Units Arbitrary units

Chromatography:

Chromatography ID:CH003833
Methods Filename:L12
Chromatography Comments:The LC column was a MilliporeTM ZIC-pHILIC (2.1 x150 mm, 5 μm) coupled to a Dionex Ultimate 3000TM system and the column oven temperature was set to 25oC for the gradient elution. A flow rate of 100 μL/min was used with the following buffers; A) 10 mM ammonium carbonate in water, pH 9.0, and B) neat acetonitrile. The gradient profile was as follows; 80-20%B (0-30 min), 20-80%B (30-31 min), 80-80%B (31-42 min). Injection volume was set to 2 μL for all analyses (42 min total run time per injection).
Instrument Name:Ulitmate 3000
Column Name:SeQuant ZIC-pHILIC (150 x 4.6mm,5um)
Column Pressure:1800
Column Temperature:25
Flow Gradient:80-20%B (0-30 min), 20-80%B (30-31 min), 80-80%B (31-42 min)
Flow Rate:0.1mL/min
Injection Temperature:4
Internal Standard:ISTD (500nM amino acid cocktail)
Sample Injection:2uL
Solvent A:100% water; 10 mM ammonium carbonate, pH 9.0
Solvent B:100% acetonitrile
Analytical Time:30m
Oven Temperature:28
Chromatography Type:HILIC
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