Library Size in Spatial ATAC-seq: Technical Confounder or Biology?
Bibliographic record
Abstract
Summary Spatially resolved assay for transposase-accessible chromatin with sequencing (spATAC-seq) is an emerging technology for studying spatial variation in gene regulatory landscapes within tissues. Current analysis pipelines commonly apply library size normalization, assuming that variation in sequencing library size across cells represents a technical confounder rather than biological signal. While recent studies have shown that library size can confound biological interpretation in spatial transcriptomics, its impact in spATAC-seq remains poorly understood. Here, we show that library size in spATAC-seq data is biologically informative and that standard normalization methods can obscure important biological signals and hinder downstream analyses. These findings underscore the need for caution and for the development of improved approaches to address library size in spATAC-seq analysis.
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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 | 0.040 | 0.083 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.005 |
| Scholarly communication | 0.005 | 0.003 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.002 | 0.005 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".