Efficient network-guided multi-locus association mapping with graph cuts

Chloé Agathe Azencott, Dominik Grimm, Mahito Sugiyama, Yoshinobu Kawahara, Karsten M. Borgwardt

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Motivation: As an increasing number of genome-wide association studies reveal the limitations of the attempt to explain phenotypic heritability by single genetic loci, there is a recent focus on associating complex phenotypes with sets of genetic loci. Although several methods for multi-locus mapping have been proposed, it is often unclear how to relate the detected loci to the growing knowledge about gene pathways and networks. The few methods that take biological pathways or networks into account are either restricted to investigating a limited number of predetermined sets of loci or do not scale to genome-wide settings.Results: We present SConES, a new efficient method to discover sets of genetic loci that are maximally associated with a phenotype while being connected in an underlying network. Our approach is based on a minimum cut reformulation of the problem of selecting features under sparsity and connectivity constraints, which can be solved exactly and rapidly.SConES outperforms state-of-the-art competitors in terms of runtime, scales to hundreds of thousands of genetic loci and exhibits higher power in detecting causal SNPs in simulation studies than other methods. On flowering time phenotypes and genotypes from Arabidopsis thaliana, SConES detects loci that enable accurate phenotype prediction and that are supported by the literature.

Original languageEnglish
Pages (from-to)i171-i179
JournalBioinformatics
Volume29
Issue number13
DOIs
Publication statusPublished - Jul 1 2013

Fingerprint

Graph Cuts
Genetic Loci
Locus
Genes
Phenotype
Gene Regulatory Networks
Genome-Wide Association Study
Arabidopsis
Single Nucleotide Polymorphism
Pathway
Genome
Genotype
Heritability
Minimum Cut
Arabidopsis Thaliana
Flowering
Reformulation
Sparsity
High Power
Connectivity

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

Cite this

Efficient network-guided multi-locus association mapping with graph cuts. / Azencott, Chloé Agathe; Grimm, Dominik; Sugiyama, Mahito; Kawahara, Yoshinobu; Borgwardt, Karsten M.

In: Bioinformatics, Vol. 29, No. 13, 01.07.2013, p. i171-i179.

Research output: Contribution to journalArticle

Azencott, CA, Grimm, D, Sugiyama, M, Kawahara, Y & Borgwardt, KM 2013, 'Efficient network-guided multi-locus association mapping with graph cuts', Bioinformatics, vol. 29, no. 13, pp. i171-i179. https://doi.org/10.1093/bioinformatics/btt238
Azencott, Chloé Agathe ; Grimm, Dominik ; Sugiyama, Mahito ; Kawahara, Yoshinobu ; Borgwardt, Karsten M. / Efficient network-guided multi-locus association mapping with graph cuts. In: Bioinformatics. 2013 ; Vol. 29, No. 13. pp. i171-i179.
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