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A reproducibility-audit framework for generalizable versus dataset- specific molecular transition boundaries in Alzheimer’s disease
Kim Y, Heo W, Park SJ, Kim Y, Cho YE.. bioRxiv, 2026-09-01
Topic: Genetics and APOE
Validated on synthetic ground truth, the audit separates a generalizable anchor (PTGDS) from a dataset-specific signal and a global-expression artefact, providing a reusable control for trajectory-based molecular staging. Motivation Single-cell atlases increasingly place disease stages at molecular transition boundaries along pseudo-progression trajectories, and the marker that anchors such a boundary is often read as biologically meaningful. Yet a boundary identified in one atlas need not recur in another region, cohort or molecular modality, and a large single-dataset effect can reflect global transcriptional amplitude rather than a specific program. No standard procedure exists to decide whether a trajectory boundary generalizes before it is interpreted. We therefore built a transferable, permutation-controlled audit with measurable operating characteristics that makes this decision explicit, and asked what it implies for one widely used atlas.
Key findings
- Validated on synthetic ground truth, the audit separates a generalizable anchor (PTGDS) from a dataset-specific signal and a global-expression artefact, providing a reusable control for trajectory-based molecular staging.
- Motivation Single-cell atlases increasingly place disease stages at molecular transition boundaries along pseudo-progression trajectories, and the marker that anchors such a boundary is often read as biologically meaningful.
- Yet a boundary identified in one atlas need not recur in another region, cohort or molecular modality, and a large single-dataset effect can reflect global transcriptional amplitude rather than a specific program.
- No standard procedure exists to decide whether a trajectory boundary generalizes before it is interpreted.
- We therefore built a transferable, permutation-controlled audit with measurable operating characteristics that makes this decision explicit, and asked what it implies for one widely used atlas.
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Study details
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 24 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 15 of the 62 points we could judge it on, which is 24 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 15 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 15 of the 62 points we could judge it on is 24 out of 100. |
| Total | 24 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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APA 7th
Kim, Y., Heo, W., Park, S. J., & Cho, Y. E. (2026). A reproducibility-audit framework for generalizable versus dataset- specific molecular transition boundaries in Alzheimer’s disease. bioRxiv. https://doi.org/10.64898/2026.08.24.746808
Vancouver
Kim Y, Heo W, Park SJ, Cho YE. A reproducibility-audit framework for generalizable versus dataset- specific molecular transition boundaries in Alzheimer’s disease. bioRxiv. 2026. doi:10.64898/2026.08.24.746808.
BibTeX
@article{kim2026-9f5c4bb5,
author = {Kim, Y. and Heo, W. and Park, S. J. and Cho, Y. E.},
title = {{A reproducibility-audit framework for generalizable versus dataset- specific molecular transition boundaries in Alzheimer’s disease}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.08.24.746808},
url = {https://doi.org/10.64898/2026.08.24.746808}
}