Evidence map›Paper›PMID 27769169›Full record

ArticleBMC genomics2016

Unexpected effects of different genetic backgrounds on identification of genomic rearrangements via whole-genome next generation sequencing.

Zhangguo Chen, Katherine Gowan, Sonia M Leach, Sawanee S Viboolsittiseri, Ameet K Mishra, Tanya Kadoishi, Katrina Diener, Bifeng Gao, Kenneth Jones, Jing H Wang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 40% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
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

10 authors at 3 institutions in 1 country.

Zhangguo ChenDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, 12800 E, 19th Ave, Mail Stop 8333, Aurora, CO, 80045, USA.
Katherine GowanDepartment of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Sonia M LeachDepartment of Biomedical Research, National Jewish Health, Denver, CO, 80206, USA.
Sawanee S ViboolsittiseriDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, 12800 E, 19th Ave, Mail Stop 8333, Aurora, CO, 80045, USA.
Ameet K MishraDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, 12800 E, 19th Ave, Mail Stop 8333, Aurora, CO, 80045, USA.
Tanya KadoishiDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, 12800 E, 19th Ave, Mail Stop 8333, Aurora, CO, 80045, USA.
Katrina DienerGenomic and Microarray Core, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Bifeng GaoGenomic and Microarray Core, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Kenneth JonesDepartment of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Jing H WangDepartment of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, 12800 E, 19th Ave, Mail Stop 8333, Aurora, CO, 80045, USA. jing.wang@ucdenver.edu.
University of Colorado Anschutz Medical Campus · USNational Jewish Health · USUniversity of Colorado Denver · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
Training in Translational Research of Lung, Head and Neck CancerT32CA174648 · NCI · UNIVERSITY OF COLORADO DENVER · PI KARAM, SANA D · 2013 to 2022
$4.2M
Mechanisms promoting translocations and mature B cell lymphomasR01CA166325 · NCI · UNIVERSITY OF COLORADO DENVER · PI WANG, JING HONG · 2012 to 2016
$1.7M
Role of Target DNA sequences in mutation and DNA Break GenerationR21AI110777 · NIAID · UNIVERSITY OF COLORADO DENVER · PI WANG, JING HONG · 2015 to 2016
$427k
Genomic instability mediated via differential DNA repair mechanisms in B cellsR21CA184707 · NCI · UNIVERSITY OF COLORADO DENVER · PI WANG, JING HONG · 2015 to 2016
$372k
NCATS NIH HHS UL1 TR001082NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA166325NCI NIH HHS R21 CA184707NCI NIH HHS T32 CA174648NIAID NIH HHS R21 AI110777
6 · The paper itself

Abstract

backgroundWhole genome next generation sequencing (NGS) is increasingly employed to detect genomic rearrangements in cancer genomes, especially in lymphoid malignancies. We recently established a unique mouse model by specifically deleting a key non-homologous end-joining DNA repair gene, Xrcc4, and a cell cycle checkpoint gene, Trp53, in germinal center B cells. This mouse model spontaneously develops mature B cell lymphomas (termed G1XP lymphomas).

resultsHere, we attempt to employ whole genome NGS to identify novel structural rearrangements, in particular inter-chromosomal translocations (CTXs), in these G1XP lymphomas. We sequenced six lymphoma samples, aligned our NGS data with mouse reference genome (in C57BL/6J (B6) background) and identified CTXs using CREST algorithm. Surprisingly, we detected widespread CTXs in both lymphomas and wildtype control samples, majority of which were false positive and attributable to different genetic backgrounds. In addition, we validated our NGS pipeline by sequencing multiple control samples from distinct tissues of different genetic backgrounds of mouse (B6 vs non-B6). Lastly, our studies showed that widespread false positive CTXs can be generated by simply aligning sequences from different genetic backgrounds of mouse.

conclusionsWe conclude that mapping and alignment with reference genome might not be a preferred method for analyzing whole-genome NGS data obtained from a genetic background different from reference genome. Given the complex genetic background of different mouse strains or the heterogeneity of cancer genomes in human patients, in order to minimize such systematic artifacts and uncover novel CTXs, a preferred method might be de novo assembly of personalized normal control genome and cancer cell genome, instead of mapping and aligning NGS data to mouse or human reference genome. Thus, our studies have critical impact on the manner of data analysis for cancer genomics.

Indexed as

Gene RearrangementGenetic BackgroundGenomeGenomicsAnimalsB-LymphocytesComputational BiologyHigh-Throughput Nucleotide SequencingLymphomaMiceMice, TransgenicReproducibility of ResultsTranslocation, GeneticB cell lymphomade novo assemblyDifferent genetic backgroundGenomic instabilityWhole genome next generation sequencing

Identifiers

PMID27769169
PMCPMC5075209
OpenAlexW2535632395

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.