Evidence map›Paper›PMID 25526783›Full record

ArticleBMC genomics2014

Sequencing methods and datasets to improve functional interpretation of sleeping beauty mutagenesis screens.

Jesse D Riordan, Luke J Drury, Ryan P Smith, Benjamin T Brett, Laura M Rogers, Todd E Scheetz, Adam J Dupuy

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.0field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 24 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Jesse D Riordan
Luke J Drury
Ryan P Smith
Benjamin T Brett
Laura M Rogers
Todd E Scheetz
Adam J DupuyDepartment of Anatomy and Cell Biology, University of Iowa, Iowa City IA 52242, USA. adam-dupuy@uiowa.edu.
University of Iowa · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Christopher K Laubenthal · 2000 to 2026
$70.0M
PROGRAM IN HEMOSTASIS AND THROMBOSIS FOR ACADEMICT32HL007344 · NHLBI · UNIVERSITY OF IOWA · PI Anil Kumar Chauhan, Steven R Lentz · 1985 to 2026
$6.5M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM008629 · NIGMS · UNIVERSITY OF IOWA · PI EBERL, DANIEL F · 1997 to 2021
$4.1M
A Genetic Screen for HCC GenesR01CA132962 · NCI · UNIVERSITY OF MINNESOTA · PI DUPUY, ADAM J., LARGAESPADA, DAVID ANDREW · 2010 to 2014
$1.5M
Genetic Determinants of Optic Nerve Head StructureR01EY023187 · NEI · UNIVERSITY OF IOWA · PI SCHEETZ, TODD E · 2013 to 2015
$1.1M
An adenoviral/piggyBac hybrid system to accelerate cancer gene validation(PQ #9)R21CA170195 · NCI · UNIVERSITY OF IOWA · PI DUPUY, ADAM J. · 2012 to 2013
$349k
NCI NIH HHS R01 CA132962NCI NIH HHS R01CA132962NCI NIH HHS R21 CA170195NCI NIH HHS R21CA170195NEI NIH HHS R01 EY023187NEI NIH HHS R01EY023187NHLBI NIH HHS HL007344NHLBI NIH HHS T32 HL007344NIGMS NIH HHS T32 GM008629
6 · The paper itself

Abstract

backgroundAnimal models of cancer are useful to generate complementary datasets for comparison to human tumor data. Insertional mutagenesis screens, such as those utilizing the Sleeping Beauty (SB) transposon system, provide a model that recapitulates the spontaneous development and progression of human disease. This approach has been widely used to model a variety of cancers in mice. Comprehensive mutation profiles are generated for individual tumors through amplification of transposon insertion sites followed by high-throughput sequencing. Subsequent statistical analyses identify common insertion sites (CISs), which are predicted to be functionally involved in tumorigenesis. Current methods utilized for SB insertion site analysis have some significant limitations. For one, they do not account for transposon footprints - a class of mutation generated following transposon remobilization. Existing methods also discard quantitative sequence data due to uncertainty regarding the extent to which it accurately reflects mutation abundance within a heterogeneous tumor. Additionally, computational analyses generally assume that all potential insertion sites have an equal probability of being detected under non-selective conditions, an assumption without sufficient relevant data. The goal of our study was to address these potential confounding factors in order to enhance functional interpretation of insertion site data from tumors.

resultsWe describe here a novel method to detect footprints generated by transposon remobilization, which revealed minimal evidence of positive selection in tumors. We also present extensive characterization data demonstrating an ability to reproducibly assign semi-quantitative information to individual insertion sites within a tumor sample. Finally, we identify apparent biases for detection of inserted transposons in several genomic regions that may lead to the identification of false positive CISs.

conclusionThe information we provide can be used to refine analyses of data from insertional mutagenesis screens, improving functional interpretation of results and facilitating the identification of genes important in cancer development and progression.

Indexed as

Mutagenesis, InsertionalAnimalsDNA Transposable ElementsFemaleHigh-Throughput Nucleotide SequencingHumansMaleMiceNeoplasmsDNA Transposable Elements

Identifiers

PMID25526783
PMCPMC4378557
OpenAlexW1879626818

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.