Unknown,Transcriptomics,Genomics,Proteomics

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RNA-seq alignment to individualized genomes


ABSTRACT: The source of most errors in RNA sequencing (RNA-seq) read alignment is in the repetitive structure of the genome and not with the alignment algorithm. Genetic variation away from the reference sequence exacerbates this problem causing reads to be assigned to the wrong location. We developed a method, implemented as the software package Seqnature, to construct the imputed genomes of individuals (individualized genomes) of experimental model organisms including inbred mouse strains and genetically unique outbred animals. Alignment to individualized genomes increases read mapping accuracy and improves transcript abundance estimates. In an application to expression QTL mapping, this approach corrected erroneous linkages and unmasked thousands of hidden associations. Individualized genomes accounting for genetic variation will be useful for human short-read sequencing and other sequencing applications including ChIP-seq. Illumina 100bp single-end liver RNA-seq from 277 male and female Diversity Outbred 26-week old mice raised on standard chow or high fat diet. In addition, Illumina 100bp single-end liver RNA-seq from 128 male 26-week old male mice (20 weeks for NZO strain) from each of the DO founder strains raised on standard chow or high fat diet (8 males per strain by diet group). Each sample was sequenced in 2-4x technical replicates across multiple flowcells. Samples were randomly assigned lanes and multiplexed at 12-24x.

ORGANISM(S): Mus musculus

SUBMITTER: Steven Munger 

PROVIDER: E-GEOD-45684 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications


RNA editing refers to post-transcriptional processes that alter the base sequence of RNA. Recently, hundreds of new RNA editing targets have been reported. However, the mechanisms that determine the specificity and degree of editing are not well understood. We examined quantitative variation of site-specific editing in a genetically diverse multiparent population, Diversity Outbred mice, and mapped polymorphic loci that alter editing ratios globally for C-to-U editing and at specific sites for A  ...[more]

Publication: 1/2

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