Evidence map›Paper›PMID 25236449›Full record

ArticleGenetics2014

RNA-Seq alignment to individualized genomes improves transcript abundance estimates in multiparent populations.

Steven C Munger, Narayanan Raghupathy, Kwangbom Choi, Allen K Simons, Daniel M Gatti, Douglas A Hinerfeld, Karen L Svenson, Mark P Keller, Alan D Attie, Matthew A Hibbs and 3 more

Abstract read
In one paragraph

Article in Genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

67 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  9. Fifteen years of the Diversity Outbred mouse model: a review.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
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  11. TheBiomolecules · 2025
    Review
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7 more citing papers are in PubMed but not listed here.

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

13 authors.

Steven C MungerThe Jackson Laboratory, Bar Harbor, Maine 04609.ORCID http://orcid.org/0000-0002-8458-1871
Narayanan RaghupathyThe Jackson Laboratory, Bar Harbor, Maine 04609.
Kwangbom ChoiThe Jackson Laboratory, Bar Harbor, Maine 04609.
Allen K SimonsThe Jackson Laboratory, Bar Harbor, Maine 04609.
Daniel M GattiThe Jackson Laboratory, Bar Harbor, Maine 04609.
Douglas A HinerfeldThe Jackson Laboratory, Bar Harbor, Maine 04609.
Karen L SvensonThe Jackson Laboratory, Bar Harbor, Maine 04609.
Mark P KellerUniversity of Wisconsin, Madison, Wisconsin 53705.
Alan D AttieUniversity of Wisconsin, Madison, Wisconsin 53705.
Matthew A HibbsThe Jackson Laboratory, Bar Harbor, Maine 04609 Trinity University, San Antonio, Texas 78212.
Joel H GraberThe Jackson Laboratory, Bar Harbor, Maine 04609.
Elissa J CheslerThe Jackson Laboratory, Bar Harbor, Maine 04609.
Gary A ChurchillThe Jackson Laboratory, Bar Harbor, Maine 04609 gary.churchill@jax.org.

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI Anna Karolina Palucka · 1985 to 2026
$61.9M
UNC and PERLEGEN, IncP50GM076468 · NIGMS · JACKSON LABORATORY · PI PETKOV, PETKO M · 2006 to 2015
$31.0M
Genetic Mapping of Networks Associated with Beta-cell D*R01DK066369 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI ATTIE, ALAN D · 2004 to 2014
$6.3M
The Genetics of Obesity and DiabetesR01DK058037 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI ATTIE, ALAN D · 2001 to 2013
$5.7M
The Diversity Outbred Diabetes ProjectR01DK101573 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI Alan D Attie · 2014 to 2026
$5.3M
The Collaborative Cross Project on Obesity and DiabetesR24DK091207 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI ATTIE, ALAN D, BRUNENGRABER, HENRI · 2011 to 2011
$517k
Sensitized Screen in the Diversity Outcross Mouse PopulationF32HD074299 · NICHD · JACKSON LABORATORY · PI MUNGER, STEVEN CARMEN · 2012 to 2014
$148k
NCI NIH HHS P30 CA034196NICHD NIH HHS F32 HD074299NICHD NIH HHS F32HD074299NIDDK NIH HHS DK091207NIDDK NIH HHS DK58037NIDDK NIH HHS DK66369NIDDK NIH HHS R01 DK058037NIDDK NIH HHS R01 DK066369NIDDK NIH HHS R01 DK101573NIDDK NIH HHS R24 DK091207NIGMS NIH HHS P50 GM076468NIGMS NIH HHS P50GM076468
6 · The paper itself

Abstract

Massively parallel RNA sequencing (RNA-seq) has yielded a wealth of new insights into transcriptional regulation. A first step in the analysis of RNA-seq data is the alignment of short sequence reads to a common reference genome or transcriptome. Genetic variants that distinguish individual genomes from the reference sequence can cause reads to be misaligned, resulting in biased estimates of transcript abundance. Fine-tuning of read alignment algorithms does not correct this problem. We have developed Seqnature software to construct individualized diploid genomes and transcriptomes for multiparent populations and have implemented a complete analysis pipeline that incorporates other existing software tools. We demonstrate in simulated and real data sets that alignment to individualized transcriptomes increases read mapping accuracy, improves estimation of transcript abundance, and enables the direct estimation of allele-specific expression. Moreover, when applied to expression QTL mapping we find that our individualized alignment strategy corrects false-positive linkage signals and unmasks hidden associations. We recommend the use of individualized diploid genomes over reference sequence alignment for all applications of high-throughput sequencing technology in genetically diverse populations.

Indexed as

SoftwareTranscriptomeAnimalsFemaleGenomeMaleMiceQuantitative Trait LociSequence AlignmentSequence Analysis, RNADiversity Outbred (DO)Diversity Outbred miceexpression QTLhaplotype reconstructionhigh-density genotypingmixed modelsMPPMultiparent Advanced Generation Inter-Cross (MAGIC)Multiparental populationsQTL mappingRNA-seq

Identifiers

PMID25236449
PMCPMC4174954

What OpenQuestion holds

Textmetadata
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.