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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 01, 2022 |
| Title |
A single-cell based precision medicine approach using glioblastoma patient specific models |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Glioblastoma (GBM) is a heterogeneous tumor made up of cell states that evolve over time. Here, we modeled tumor evolutionary trajectories during standard-of-care treatment using multi-omic single-cell analysis of a primary tumor sample, corresponding mouse xenografts subjected to standard of care therapy, and recurrent tumor at autopsy. We mined the multi-omic data with single cell SYstems Genetics Network AnaLysis (scSYGNAL) to identify a network of 52 regulators that mediate treatment-induced shifts in xenograft tumor-cell states that were also reflected in recurrence. By integrating scSYGNAL-derived regulatory network information with transcription factor accessibility deviations derived from single-cell ATAC-seq data, we developed consensus networks that modulate cell state transitions across subpopulations of primary and recurrent tumor cells. Finally, by matching targeted therapies to active regulatory networks underlying tumor evolutionary trajectories, we provide a framework for applying single-cell-based precision medicine approaches in a concurrent, adjuvant, or recurrent setting.
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| Overall design |
Single-cell RNA-sequencing of primary GBM tumor and recurrent GBM tumor (Samples 1 and 3). Additional single-cell RNA-sequencing was performed on PDX samples post 24hrs and 72hrs treated with fractionated radiotherapy and temozolomide and corresponding untreated control samples (Sample 2).
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| Contributor(s) |
Park J, Feroze AH, Emerson SN, Mihalas AB, Keene CD, Cimino PJ, Garcia de Lomana AL, Kannan K, Wu W, Turkarslan S, Baliga NS, Patel AP |
| Citation(s) |
35941215 |
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| Submission date |
Nov 26, 2021 |
| Last update date |
Aug 24, 2022 |
| Contact name |
James H. Park |
| E-mail(s) |
james.park@isbscience.org
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| Organization name |
Institute for Systems Biology
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| Street address |
1736 Belmont ave, Apt 105
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98122 |
| Country |
USA |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA783941 |
| SRA |
SRP348120 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE189650_RAW.tar |
1.4 Gb |
(http)(custom) |
TAR (of CSV, H5, MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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