Identifying, understanding, and correcting technical artifacts on the sex chromosomes in next-generation sequencing data
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
BACKGROUND: Mammalian X and Y chromosomes share a common evolutionary origin and retain regions of high sequence similarity. Similar sequence content can confound the mapping of short next-generation sequencing reads to a reference genome. It is therefore possible that the presence of both sex chromosomes in a reference genome can cause technical artifacts in genomic data and affect downstream analyses and applications. Understanding this problem is critical for medical genomics and population genomic inference. RESULTS: Here, we characterize how sequence homology can affect analyses on the sex chromosomes and present XYalign, a new tool that (1) facilitates the inference of sex chromosome complement from next-generation sequencing data; (2) corrects erroneous read mapping on the sex chromosomes; and (3) tabulates and visualizes important metrics for quality control such as mapping quality, sequencing depth, and allele balance. We find that sequence homology affects read mapping on the sex chromosomes and this has downstream effects on variant calling. However, we show that XYalign can correct mismapping, resulting in more accurate variant calling. We also show how metrics output by XYalign can be used to identify XX and XY individuals across diverse sequencing experiments, including low- and high-coverage whole-genome sequencing, and exome sequencing. Finally, we discuss how the flexibility of the XYalign framework can be leveraged for other uses including the identification of aneuploidy on the autosomes. XYalign is available open source under the GNU General Public License (version 3). CONCLUSIONS: Sex chromsome sequence homology causes the mismapping of short reads, which in turn affects downstream analyses. XYalign provides a reproducible framework to correct mismapping and improve variant calling on the sex chromsomes.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| 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 | 0.000 | 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