CEP-IP with CMRF in SEA-AD Microglia: A Mitochondrial Co-expression Module Linked to Cognition
Wong KK.. bioRxiv, 2026-10-27
Topic: Inflammation, microglia and astrocytes
Single-nucleus RNA-seq (snRNA-seq) studies of Alzheimer’s disease (AD) routinely filter nuclei by mitochondrial percentage (%MT) or remove mitochondrial genes, yet whether these reads carry information about cognition is rarely examined. In the SEA-AD microglia snRNA-seq dataset, a transcriptome-wide screen identified a module of MT-CO3 and eight co-expressed mitochondrial genes. Three microglial populations were analyzed: M4 (Mic.13-like), PVM_3, and PVM_1, with a housekeeping-gene control in M4 cells. The CEP-IP pipeline with a copula monotone recovery filter (CMRF) used per-cell Spearman and Kendall scores, an inflection point (IP), and a cross-validated copula space boundary to isolate MT-CO3 Module cells. The donor percentage of Module cells past the IP (Module post-IP%) was significantly associated with worse cognition (MMSE and CASI; FDR<0.05) in all three populations. In M4 and PVM_3, these associations remained significant after adjustment for tissue quality, plaque burden, tangle burden, and contamination, and after doublet removal. M4 and PVM_3 Module post-IP% repeated in each donor’s regions beyond chance, and no per-cell %MT cutoff reproduced the Module cells. However, at the donor level, Module post-IP% could not be separated from mean %MT, and the source of the mitochondrial transcripts (e.g., retained cytoplasm or a true change in mitochondrial content) remains unresolved. Routine %MT filtering in AD snRNA-seq may therefore remove cells that carry information about cognition. The full pipeline code, software container, processed data, and the R package cepip are publicly available, and reruns of the full pipeline in the container reproduced the original findings.
Key findings
- The donor percentage of Module cells past the IP (Module post-IP%) was significantly associated with worse cognition (MMSE and CASI; FDR<0.05) in all three populations.
- In M4 and PVM_3, these associations remained significant after adjustment for tissue quality, plaque burden, tangle burden, and contamination, and after doublet removal.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 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 13 of the 62 points we could judge it on, which is 21 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 | 1 / 5 | Rated “low” 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 | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Wong, K. K. (2026). CEP-IP with CMRF in SEA-AD Microglia: A Mitochondrial Co-expression Module Linked to Cognition. bioRxiv. https://doi.org/10.64898/2026.10.22.761284
Vancouver
Wong KK. CEP-IP with CMRF in SEA-AD Microglia: A Mitochondrial Co-expression Module Linked to Cognition. bioRxiv. 2026. doi:10.64898/2026.10.22.761284.
BibTeX
@article{wong2026-d98194dd,
author = {Wong, K. K.},
title = {{CEP-IP with CMRF in SEA-AD Microglia: A Mitochondrial Co-expression Module Linked to Cognition}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.22.761284},
url = {https://doi.org/10.64898/2026.10.22.761284}
}
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