Topic: Genetics and APOE
Multi-subject spatial transcriptomics is increasingly used to identify molecular differences across individuals and conditions while resolving where in tissue those differences occur. Yet subject-level differential expression (DE) analyses commonly require spatial regions to be specified in advance, separating localization from testing. Here we present SpaceDX, a framework that uses gene-specific attention-based spatial weighting to jointly test differential expression and localize the spatial expression patterns contributing to these associations. In simulations, SpaceDX outperforms cluster-based DE methods when differential expression does not align with predefined spatial boundaries. Across two multi-subject mouse brain datasets, SpaceDX detected 45.8% more DE genes than regional DESeq2 pseudobulk in a chronic stress model, while in an Alzheimer's disease model combining SpaceDX with DESeq2 increased discovery by 19.1% relative to DESeq2 alone. Across both datasets, the learned maps provided spatial context for condition-associated expression signals in addition to gene-level significance. In the chronic stress model, for example, oligodendrocyte- and myelin-associated genes showed shared localization to corresponding brain structures. Together, these results show that the spatial context of differential expression can be inferred jointly with gene-level associations, recovering signals obscured by regional aggregation without requiring the relevant tissue context to be defined in advance.
Key findings
- Together, these results show that the spatial context of differential expression can be inferred jointly with gene-level associations, recovering signals obscured by regional aggregation without requiring the relevant tissue context to be defined in advance.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Effect size45.8%; 19.1%
- Evidence strengthLow
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Preprint — not yet peer-reviewed.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, 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 | 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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
Stotzem, N., Chang, S., Cai, N., & Casale, F. P. (2026). Joint localization and testing reveals spatial context of differential expression. bioRxiv. https://doi.org/10.64898/2026.10.28.758685
Vancouver
Stotzem N, Chang S, Cai N, Casale FP. Joint localization and testing reveals spatial context of differential expression. bioRxiv. 2026. doi:10.64898/2026.10.28.758685.
BibTeX
@article{stotzem2026-fb708898,
author = {Stotzem, N. and Chang, S. and Cai, N. and Casale, F. P.},
title = {{Joint localization and testing reveals spatial context of differential expression}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.28.758685},
url = {https://doi.org/10.64898/2026.10.28.758685}
}