Abstract B6: Human genome contains a large number of very long intergenic transcribed regions, some of which are associated with cancer outcome
Notice bibliographique
Résumé
Abstract Introduction: Transcriptional output of human genome is far more complex than predicted by the current set of protein-coding annotations. However, the fraction of the genome that is utilized to produce cellular RNA whose function is hitherto not completely defined, the so called “dark matter RNA”, and its role in regulating cancer progression remains an open issue. Furthermore, our understanding of the repertoire of human RNAs is far from complete, and almost all RNA-Seq studies have missed this complexity due to the limited view obtained when only interrogating the polyA+ RNA fraction confounded by biases due to PCR amplifications. This study aimed to assess the complexity of RNAs produced by cancerous and normal human tissues in an unbiased fashion, and examine any potential roles of such transcripts in modulating cancer outcome using pediatric rhabdomyosarcoma as a model malignancy. Methods: Total RNA was profiled from a number of tissues using single-molecule sequencing (SMS) to examine the complexity of transcriptome in the human genome in an unbiased fashion. To minimize methodological biases, no PCR amplification, ligation, or size selection were used. In parallel, to examine the relevance of different RNAs in predicting cancer outcome, expression profiles on 79 intermediate-risk childhood rhabdomyosarcoma primary tumors were generated on Affymetrix Human Exon 1.0 ST microarrays and compared to prospectively-obtained outcome information. Results: SMS analysis revealed that “dark matter RNAs” comprised up to two-thirds of total non-ribosomal, non-mitochondrial RNA in human cells. PolyA+ RNA fraction had a significantly lower complexity then the total RNA, especially in non-exonic regions. Strikingly, several hundreds of very long (100′s of kbs) abundant intergenic transcribed regions (vlinc's) were identified in areas of the genome that were devoid of protein-coding annotations. Most (~80%) of the genomic sequences covered by vlincs did not overlap with previously documented long intergenic non-coding (linc) RNAs, suggesting large number of RNAs in intergenic space are yet to be uncovered. To address the question whether vlincs may be associated with prognosis in cancer, specifically childhood rhabdomyosarcoma, array-based whole-genome expression profiles were analyzed. Interestingly, probe sets that were the best predictors of cancer outcome were found to be outside boundaries of exons of protein-coding transcripts. Strikingly, most of the top-ranked probe sets were found to cluster together and defined a >230 kb vlinc region on chromosome 2, previously found by the SMS analysis. This vlinc region was singularly able to predict survival for the entire cohort (p=0.007). Conclusions: Our data suggest that many genomic regions currently defined as intergenic give rise to very long transcribed regions that can modulate ultimate cancer behavior. This indicates that a great number of the “dark matter” RNAs uncharacterized thus far may be involved in tumorigenesis, and can be used as diagnostic, prognostic and therapeutic-response indicators. In turn, this argues for functional importance of the genome's “dark matter”. Citation Format: Anirban P. Mitra, Timothy J. Triche, Sheetal A. Mitra, Jonathan D. Buckley, Poul H. B. Sorensen, C Patrick Reynolds, Robert J. Arceci, Patrice Milos, Georges St. Laurent, Philipp Kapranov. Human genome contains a large number of very long intergenic transcribed regions, some of which are associated with cancer outcome [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr B6.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,003 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».