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.
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 | ST003102 |
Study Title | Cellular adaptation to cancer therapy occurs by progressive state transitions along a resistance continuum |
Study Summary | Recent 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 Name | Starvaggi Franca |
First Name | Gustavo |
Address | 430 East 29th Street, NY NY 10016 |
Gustavo.StarvaggiFranca@nyulangone.org | |
Phone | 6465015151 |
Submit Date | 2024-02-13 |
Raw Data Available | Yes |
Raw Data File Type(s) | mzXML |
Analysis Type Detail | LC-MS |
Release Date | 2024-04-02 |
Release Version | 1 |
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Combined analysis:
Analysis ID | AN005076 |
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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 |