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

MS:

MS ID:MS004814
Analysis ID:AN005076
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:M.13 Polar metabolites (pHILIC Hybrid). MS analyses were carried out by coupling the LC system to a Thermo Q Exactive HFTM mass spectrometer operating in heated electrospray ionization mode (HESI). Method duration was 30 min with a polarity switching data-dependent Top 5 method for both positive and negative modes. Spray voltage for both positive and negative modes was 3.5kV and capillary temperature was set to 320oC with a sheath gas rate of 35, aux gas of 10, and max spray current of 100 μA. The full MS scan for both polarities utilized 120,000 resolution with an AGC target of 3e6 and a maximum IT of 100 ms, and the scan range was from 67-1000 m/z. Tandem MS spectra for both positive and negative mode used a resolution of 15,000, AGC target of 1e5, maximum IT of 50 ms, isolation window of 0.4 m/z, isolation offset of 0.1 m/z, fixed first mass of 50 m/z, and 3-way multiplexed normalized collision energies (nCE) of 10, 35, 80. The minimum AGC target was 1e4 with an intensity threshold of 2e5. All data were acquired in profile mode.
Ion Mode:UNSPECIFIED
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