High-throughput interpretation of gene structure changes in human and nonhuman resequencing data, using ACE

Majoros, W. H., Campbell, M. S., Holt, C., DeNardo, E., Ware, D., Allen, A. S., Yandell, M., Reddy, T. E. (May 2017) High-throughput interpretation of gene structure changes in human and nonhuman resequencing data, using ACE. Bioinformatics, 33 (10). pp. 1437-1446. ISSN 1367-4811 (Electronic)1367-4803 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/28011790
DOI: 10.1093/bioinformatics/btw799


MOTIVATION: The accurate interpretation of genetic variants is critical for characterizing genotype-phenotype associations. Because the effects of genetic variants can depend strongly on their local genomic context, accurate genome annotations are essential. Furthermore, as some variants have the potential to disrupt or alter gene structure, variant interpretation efforts stand to gain from the use of individualized annotations that account for differences in gene structure between individuals or strains. RESULTS: We describe a suite of software tools for identifying possible functional changes in gene structure that may result from sequence variants. ACE ("Assessing Changes to Exons") converts phased genotype calls to a collection of explicit haplotype sequences, maps transcript annotations onto them, detects gene-structure changes and their possible repercussions, and identifies several classes of possible loss of function. Novel transcripts predicted by ACE are commonly supported by spliced RNA-seq reads, and can be used to improve read alignment and transcript quantification when an individual-specific genome sequence is available. Using publicly-available RNA-seq data, we show that ACE predictions confirm earlier results regarding the quantitative effects of nonsense-mediated decay, and we show that predicted loss-of-function events are highly concordant with patterns of intolerance to mutations across the human population. ACE can be readily applied to diverse species including animals and plants, making it a broadly useful tool for use in eukaryotic population-based resequencing projects, particularly for assessing the joint impact of all variants at a locus. AVAILABILITY: ACE is written in open-source C++ and Perl and is available from geneprediction.org/ACE CONTACT: bmajoros@duke.edu SUPPLEMENTARY INFORMATION: Supplementary information is available at Bioinformatics online.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics > computers > computer software
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
CSHL Authors:
Communities: CSHL labs > Ware lab
Depositing User: Matt Covey
Date: 15 May 2017
Date Deposited: 04 Jan 2017 15:57
Last Modified: 07 Jul 2021 13:40
PMCID: PMC5860548
Related URLs:
URI: https://repository.cshl.edu/id/eprint/33949

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving