SINGLE CELL DERIVED CLONAL ANALYSIS OF HUMAN GLIOBLASTOMA LINKS FUNCTIONAL AND GENOMIC HETEROGENEITY
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: Glioblastoma (GBM) is a cancer comprised of morphologically, genetically and phenotypically diverse cells. However, an understanding of the functional significance of intratumoral heterogeneity is lacking. METHODS: We devised a method to isolate and functionally profile tumorigenic clones from patient glioblastoma samples. RESULTS: Individual clones demonstrated unique proliferation and differentiation abilities. Importantly, naïve patient tumors included clones that were temozolomide (TMZ) resistant, indicating that resistance to conventional GBM therapy preexists in untreated tumors at a clonal level. Further, candidate therapies for resistant clones were identified with clone-specific drug screening. Genomic analyses identified genes and pathways that associate with specific functional behavior of single clones. In particular, increased expression and signaling of the autocrine/paracrine γ-aminobutyric acid (GABA) receptor GABRA3 correlates with TMZ sensitivity and patient outcome. CONCLUSIONS: Our results suggest that functional clonal profiling used to identify tumorigenic and drug resistant tumor clones will lead to the discovery of new GBM clone-specific treatment strategies. SECONDARY CATEGORY: n/a.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it