Rapid canalization of chromosome conformation-transcription fingerprints during embryogenesis revealed by fully-automated cell identity decoding with CeSCALE
Bibliographic record
Abstract
Abstract Genome organization into higher-order active and inactive compartments exhibits cell-type specific patterns, which are widely implicated in the regulation of transcriptional activity. During embryogenesis, epigenetic regulation controls cell type specification along cellular lineages with similar transcriptional identities through the coordinated action of chromatin states. However, prevalent single-molecule variability in higher-order chromosome conformation and a lack of precise cell lineage information have previously limited our understanding of the relationship between conformation and transcriptional activity in vivo . Specifically, how the conformation-transcription relationship is inherited along cellular lineages through cell divisions is poorly understood. Here, we developed a novel algorithm for cell lineage identification ( C. elegans Sinkhorn-based Cell ALignmEnt, CeSCALE) combined with single cell genomics to reveal that local conformation-transcription ‘fingerprints’ are associated with, and inherited along the stereotyped cellular lineages of C. elegans embryos. Inspired by Optimal Transport theory, CeSCALE provides a fully automated framework for quantifying lineage-resolved individual cell phenotypes in situ , across a wide developmental window. Combining CeSCALE with single-molecule chromosome tracing uncovered higher-order interchromosomal block associations, which surprisingly coalesce transcriptionally diverse domains and are independent of lineage identity. Instead, by integrating lineage-resolved chromosome conformations with single-cell transcriptomics, we find that local conformation-transcription spatial relationships (‘fingerprints’), containing both hubs and islands of transcriptional activity, are robustly inherited along lineages. Finally, we find that the canalization of these ‘fingerprints’ represent the rewiring of chromatin states at key developmental stages. Our results suggest that local chromatin environments, but not large-scale compartments, coordinate the dramatically changing transcriptome during embryogenesis.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| 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".