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Record W3118238647 · doi:10.1101/gr.257246.119

Accurate and efficient detection of gene fusions from RNA sequencing data

2021· article· en· W3118238647 on OpenAlexfundno aff
Sebastian Uhrig, Julia Ellermann, Tatjana Walther, Pauline Burkhardt, Martina Fröhlich, Barbara Hutter, Umut H. Toprak, Olaf Neumann, Albrecht Stenzinger, Claudia Scholl, Stefan Fröhling, Benedikt Brors

Bibliographic record

VenueGenome Research · 2021
Typearticle
Languageen
FieldMedicine
TopicPancreatic and Hepatic Oncology Research
Canadian institutionsnot available
FundersHeidelberger Zentrum für Personalisierte Onkologie Deutsches Krebsforschungszentrum In Der Helmholtz-GemeinschaftNationales Centrum für Tumorerkrankungen HeidelbergOntario Institute for Cancer ResearchGovernment of OntarioDeutsches Krebsforschungszentrum
KeywordsKRASBiologyFusion geneROS1Computational biologyDruggabilityGeneCancerIdentification (biology)Cancer researchBioinformaticsMutationGeneticsAdenocarcinoma

Abstract

fetched live from OpenAlex

The identification of gene fusions from RNA sequencing data is a routine task in cancer research and precision oncology. However, despite the availability of many computational tools, fusion detection remains challenging. Existing methods suffer from poor prediction accuracy and are computationally demanding. We developed Arriba, a novel fusion detection algorithm with high sensitivity and short runtime. When applied to a large collection of published pancreatic cancer samples ( n = 803), Arriba identified a variety of driver fusions, many of which affected druggable proteins, including ALK, BRAF, FGFR2, NRG1, NTRK1, NTRK3, RET, and ROS1. The fusions were significantly associated with KRAS wild-type tumors and involved proteins stimulating the MAPK signaling pathway, suggesting that they substitute for activating mutations in KRAS . In addition, we confirmed the transforming potential of two novel fusions, RRBP1 - RAF1 and RASGRP1 - ATP1A1 , in cellular assays. These results show Arriba's utility in both basic cancer research and clinical translation.

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)0.003
metaresearch head score (Gemma)0.009
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.003
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.009
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.001
Science and technology studies0.0010.000
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0010.002

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.

Opus teacher head0.266
GPT teacher head0.450
Teacher spread0.183 · 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 designBench or experimental
Domainnot available
GenreMethods

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

Citations524
Published2021
Admission routes1
Has abstractyes

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