Mining Mammalian Transcript Data for Functional Long Non-Coding RNAs
Bibliographic record
Abstract
BACKGROUND: The role of long non-coding RNAs (lncRNAs) in controlling gene expression has garnered increased interest in recent years. Sequencing projects, such as Fantom3 for mouse and H-InvDB for human, have generated abundant data on transcribed components of mammalian cells, the majority of which appear not to be protein-coding. However, much of the non-protein-coding transcriptome could merely be a consequence of 'transcription noise'. It is therefore essential to use bioinformatic approaches to identify the likely functional candidates in a high throughput manner. PRINCIPAL FINDINGS: We derived a scheme for classifying and annotating likely functional lncRNAs in mammals. Using the available experimental full-length cDNA data sets for human and mouse, we identified 78 lncRNAs that are either syntenically conserved between human and mouse, or that originate from the same protein-coding genes. Of these, 11 have significant sequence homology. We found that these lncRNAs exhibit: (i) patterns of codon substitution typical of non-coding transcripts; (ii) preservation of sequences in distant mammals such as dog and cow, (iii) significant sequence conservation relative to their corresponding flanking regions (in 50% cases, flanking regions do not have homology at all; and in the remaining, the degree of conservation is significantly less); (iv) existence mostly as single-exon forms (8/11); and, (v) presence of conserved and stable secondary structure motifs within them. We further identified orthologous protein-coding genes that are contributing to the pool of lncRNAs; of which, genes implicated in carcinogenesis are significantly over-represented. CONCLUSION: Our comparative mammalian genomics approach coupled with evolutionary analysis identified a small population of conserved long non-protein-coding RNAs (lncRNAs) that are potentially functional across Mammalia. Additionally, our analysis indicates that amongst the orthologous protein-coding genes that produce lncRNAs, those implicated in cancer pathogenesis are significantly over-represented, suggesting that these lncRNAs could play an important role in cancer pathomechanisms.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.005 | 0.006 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".