Topic: Genetics and APOE
For a long time, the protein coding potential of our genome was underestimated. Only 2% of the genome was thought to be coding for the protein while the rest was called non-coding and junk. The two main sources of biasness which resulted in underestimation were prioritising conservation and length of the open reading frames (ORFs). But recent Ribo-seq studies and high throughput quantitative proteomics studies have shown that many ORFs previously annotated as non-coding are actually getting translated into proteins and these non-canonical proteins do have certain biological functions. These findings have added more parameter perspectives to look from about different diseases. This study aims to understand translation dynamics of these proteins encoded from non-canonical ORFs in neurological disorders affecting cognitive functions specifically targeting fusiform gyrus which is linked with face recognition and anime associations which are crucial symptoms in neurological disorders. This study uses transcriptomics and proteomics analysis to understand transcriptional and translational dynamics of ncORFs. A patient cohort from the Banner Sun Health Research Institute cohort is used, corresponding RNA-seq data and Quantitative MS/MS proteomics data published in different studies are used. A custom-made protein search database was created using transcriptomics tools like STAR, StringTie and Salmon to filter out expressed ncORFs within the non-coding region and not annotated as protein coding in either GENCODE or UniProt annotations. The custom ncORF-database was then later used in proteomics analysis as search space along with the canonical proteins. The entire comprehensive analysis has resulted in identification of 22,135 ncORF-encode proteins (ncPs) and out of which 67 are differentially expressed across different neurological conditions based on the | log2FC | >1 & p.adj < 0.05 criteria. The study highlights new molecular players which might be the missing links of known mechanisms.
Key findings
- But recent Ribo-seq studies and high throughput quantitative proteomics studies have shown that many ORFs previously annotated as non-coding are actually getting translated into proteins and these non-canonical proteins do have certain biological functions.
- These findings have added more parameter perspectives to look from about different diseases.
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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. |
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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
Panchal, K., & Majumdar, S. (2026). Non-canonical proteoforms of the human fusiform gyrus in Alzheimer’s disease. bioRxiv. https://doi.org/10.64898/2026.10.20.760462
Vancouver
Panchal K, Majumdar S. Non-canonical proteoforms of the human fusiform gyrus in Alzheimer’s disease. bioRxiv. 2026. doi:10.64898/2026.10.20.760462.
BibTeX
@article{panchal2026-4e5198c5,
author = {Panchal, K. and Majumdar, S.},
title = {{Non-canonical proteoforms of the human fusiform gyrus in Alzheimer’s disease}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.20.760462},
url = {https://doi.org/10.64898/2026.10.20.760462}
}
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