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Alternative Splicing in the Mammalian Nervous System

2009· article· en· W394841860 on OpenAlexaffabout
Benjamin J. Blencowe

Bibliographic record

VenueThe FASEB Journal · 2009
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsBiologyNervous systemAlternative splicingExonRNA splicingIntronComputational biologyGeneticsGeneRNANeuroscience

Abstract

fetched live from OpenAlex

Alternative splicing is widely considered to be a major mechanism underlying the evolution of increased cellular and functional complexity in vertebrate species and is especially prevalent in the mammalian nervous system. Microarray profiling and, more recently, high‐throughput sequencing has resulted in the identification of a myriad of nervous system‐regulated exons. Many of these are located in widely expressed genes that have critical nervous system‐specific functions. Our research is currently focusing on elucidating the cis ‐acting "code" and corresponding trans‐acting factors responsible for the regulation of these exons, and their specific roles in nervous system formation and function. In collaboration with the group of Brendan Frey (Dept. of Electrical and Computer Engineering, University of Toronto) we have developed a new machine learning algorithm that can predict nervous system and other tissue‐regulated alternative splicing patterns from sequence features alone. Using other genome‐wide strategies as well as focused experimental methods we are identifying and characterizing trans ‐acting factors that link to specific elements of the cis ‐regulatory code. A new trans ‐acting factor emerging from one of the screens is the neural‐specific SR‐related protein of 100 kDa (nSR100). This protein is vertebrate‐lineage‐specific and functions as a coactivator to regulate ~10‐12% of nervous‐system specific exons via C/U‐rich motifs concentrated in flanking intron sequences. Knockdown of this protein disrupts the regulation of a network of alternative exons associated with neuronal differentiation and nervous system development.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

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.

Opus teacher head0.015
GPT teacher head0.273
Teacher spread0.258 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2009
Admission routes2
Has abstractyes

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