Evidence map›Paper›PMID 29925311›Full record

ArticleBMC genomics2018

Whole exome sequencing in the rat.

Julie F Foley, Dhiral P Phadke, Owen Hardy, Sara Hardy, Victor Miller, Anup Madan, Kellie Howard, Kimberly Kruse, Cara Lord, Sreenivasa Ramaiahgari and 6 more

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 37% 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

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Rat and Mouse Brain Tumor Models for Experimental Neuro-Oncology Research.Journal of neuropathology and experimental neurology · 2022
    Review
  5. Article
  6. 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

16 authors at 5 institutions in 1 country.

Julie F FoleyBiomolecular Screening Branch, National Institute of Environmental Health Sciences, 111 T.W. Alexander Dr. Research Triangle Park, Durham, NC, USA. foley1@niehs.nih.gov.ORCID http://orcid.org/0000-0001-9726-2821
Dhiral P PhadkeSciome, LLC, Research Triangle Park, Durham, NC, USA.
Owen HardyAgilent Technologies, Santa Clara, CA, USA.
Sara HardyAgilent Technologies, Santa Clara, CA, USA.
Victor MillerAgilent Technologies, Santa Clara, CA, USA.
Anup MadanCovance Genomics Laboratory, Redmond, WA, USA.
Kellie HowardAdaptive Biotechnologies, Seattle, WA, USA.
Kimberly KruseAdaptive Biotechnologies, Seattle, WA, USA.
Cara LordCovance Genomics Laboratory, Redmond, WA, USA.
Sreenivasa RamaiahgariBiomolecular Screening Branch, National Institute of Environmental Health Sciences, 111 T.W. Alexander Dr. Research Triangle Park, Durham, NC, USA.
Gregory G SolomonEpigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA.
Ruchir R ShahSciome, LLC, Research Triangle Park, Durham, NC, USA.
Arun R PandiriCellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA.
Ronald A HerbertCellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA.
Robert C SillsCellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA.
B Alex MerrickBiomolecular Screening Branch, National Institute of Environmental Health Sciences, 111 T.W. Alexander Dr. Research Triangle Park, Durham, NC, USA.
National Institute of Environmental Health Sciences · USAgilent Technologies (United States) · USTriangle · USAdaptive Biotechnologies (United States) · USCovance (United States) · US

Funding

CMPB Pathology Support GroupZICES102505 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI HERBERT, RONALD · 2014 to 2021
$67.7M
6 · The paper itself

Abstract

backgroundThe rat genome was sequenced in 2004 with the aim to improve human health altered by disease and environmental influences through gene discovery and animal model validation. Here, we report development and testing of a probe set for whole exome sequencing (WES) to detect sequence variants in exons and UTRs of the rat genome. Using an in-silico approach, we designed probes targeting the rat exome and compared captured mutations in cancer-related genes from four chemically induced rat tumor cell lines (C6, FAT7, DSL-6A/C1, NBTII) to validated cancer genes in the human database, Catalogue of Somatic Mutations in Cancer (COSMIC) as well as normal rat DNA. Paired, fresh frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) liver tissue from naive rats were sequenced to confirm known dbSNP variants and identify any additional variants.

resultsInformatics analysis of available gene annotation from rat RGSC6.0/rn6 RefSeq and Ensembl transcripts provided 223,636 unique exons representing a total of 26,365 unique genes and untranslated regions. Using this annotation and the Rn6 reference genome, an in-silico probe design generated 826,878 probe sequences of which 94.2% were uniquely aligned to the rat genome without mismatches. Further informatics analysis revealed 25,249 genes (95.8%) covered by at least one probe and 23,603 genes (93.5%) had every exon covered by one or more probes. We report high performance metrics from exome sequencing of our probe set and Sanger validation of annotated, highly relevant, cancer gene mutations as cataloged in the human COSMIC database, in addition to several exonic variants in cancer-related genes.

conclusionsAn in-silico probe set was designed to enrich the rat exome from isolated DNA. The platform was tested on rat tumor cell lines and normal FF and FFPE liver tissue. The method effectively captured target exome regions in the test DNA samples with exceptional sensitivity and specificity to obtain reliable sequencing data representing variants that are likely chemically induced somatic mutations. Genomic discovery conducted by means of high throughput WES queries should benefit investigators in discovering rat genomic variants in disease etiology and in furthering human translational research.

Indexed as

AnimalsCyclin-Dependent Kinase Inhibitor p16ExomeExome SequencingHigh-Throughput Nucleotide SequencingHumansMiceRatsSequence Analysis, DNATissue FixationCyclin-Dependent Kinase Inhibitor p16C6COSMICDSL-6A/C1FAT7NBTIINext generation sequencingSangerWhole exome sequencing

Identifiers

PMID29925311
PMCPMC6011395
OpenAlexW2808994919

What Socratic 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 Socratic graph.