Functional annotation of genomic variants in studies of late-onset Alzheimer's disease

Bioinformatics. 2018 Aug 15;34(16):2724-2731. doi: 10.1093/bioinformatics/bty177.

Abstract

Motivation: Annotation of genomic variants is an increasingly important and complex part of the analysis of sequence-based genomic analyses. Computational predictions of variant function are routinely incorporated into gene-based analyses of rare-variants, though to date most studies use limited information for assessing variant function that is often agnostic of the disease being studied.

Results: In this work, we outline an annotation process motivated by the Alzheimer's Disease Sequencing Project, illustrate the impact of including tissue-specific transcript sets and sources of gene regulatory information and assess the potential impact of changing genomic builds on the annotation process. While these factors only impact a small proportion of total variant annotations (∼5%), they influence the potential analysis of a large fraction of genes (∼25%).

Availability and implementation: Individual variant annotations are available via the NIAGADS GenomicsDB, at https://www.niagads.org/genomics/ tools-and-software/databases/genomics-database. Annotations are also available for bulk download at https://www.niagads.org/datasets. Annotation processing software is available at http://www.icompbio.net/resources/software-and-downloads/.

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / genetics*
  • Databases, Genetic
  • Genetic Predisposition to Disease*
  • Genome
  • Genomics
  • Humans
  • Molecular Sequence Annotation / methods*
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA / methods*
  • Software*