Reconsidering proteomic diversity with functional investigation of small ORFs and alternative ORFs
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
The discovery of functional yet non-annotated open reading frames (ORFs) throughout the genome of several species presents an unprecedented challenge in current genome annotation. These novel ORFs are shorter than annotated ones and many can be found on the same RNA, in opposition to current assumptions in annotation methodologies. Whilst the literature lacks consensus, these novel ORFs are commonly referred to as small ORFs (sORFs) or alternative ORFs (alt-ORFs). Unannotated ORFs represent an overlooked layer of complexity in the coding potential of genomes and are transforming our current vision of the nature of coding genes. In this review, we outline what constitutes a sORF or an alt-ORF and emphasize differences between both nomenclatures. We then describe complementary large-scale methods to accurately discover novel ORFs as well as yield functional insights on the novel proteins they encode. While serendipitous discoveries highlighted the functional importance of some novel ORFs, omics methods facilitate and improve their characterization to better understand physiological and pathological pathways. Functional annotation of sORFs, alt-ORFs and their corresponding microproteins will likely help fundamental and clinical research.
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 | 0.000 | 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 | 0.001 |
| 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