Resolving Subclonal Variation in Pancreatic Ductal Adenocarcinoma with Single Cell Whole Genome Sequencing
Bibliographic record
Abstract
Pancreatic ductal adenocarcinoma (PDA) is a lethal disease that presents at an advanced stage, and the mutational processes that drive progression are poorly understood. Whole genome duplication (WGD) is a hallmark of many tumour types, increases in frequency in late-stage tumors and predicts poorer overall patient survival. The genome-wide instability that occurs during WGD can promote tumor progression, but little is known about these events at the subclonal level. We performed single cell whole genome sequencing (scWGS) on 10,286 cells from 8 primary PDA tumours and inferred ploidy and genomic copy numbers for each cell. WGD was identified in 5/8 tumours (63%), 2 of which were clonal and 3 and subclonal. Clustering of copy number profiles revealed 2-5 distinct subclones per tumour, though no trend of WGD+ tumours being more diverse was observed. Phylogenetic inference reveals WGD+ clones follow a punctuated pattern of evolution, where many copy number aberrations (CNAs) were acquired rapidly in bursts with few or no intermediate cells. These data show WGD is more common in primary PDA than previously understood and a major driver of rapid CNA accumulation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".