title: Linkage disequilibrium based genotype calling from low-coverage shotgun sequencing reads.
abstract: BACKGROUND
  Recent technology advances have enabled sequencing of individual genomes, promising to revolutionize biomedical research. However, deep sequencing remains more expensive than microarrays for performing whole-genome SNP genotyping.
  
  
  RESULTS
  In this paper we introduce a new multi-locus statistical model and computationally efficient genotype calling algorithms that integrate shotgun sequencing data with linkage disequilibrium (LD) information extracted from reference population panels such as Hapmap or the 1000 genomes project. Experiments on publicly available 454, Illumina, and ABI SOLiD sequencing datasets suggest that integration of LD information results in genotype calling accuracy comparable to that of microarray platforms from sequencing data of low-coverage. A software package implementing our algorithm, released under the GNU General Public License, is available at http://dna.engr.uconn.edu/software/GeneSeq/.
  
  
  CONCLUSIONS
  Integration of LD information leads to significant improvements in genotype calling accuracy compared to prior LD-oblivious methods, rendering low-coverage sequencing as a viable alternative to microarrays for conducting large-scale genome-wide association studies.
authors.affiliation: Department of Computer Science & Engineering, University of Connecticut, 371 Fairfield Rd, Unit 2155, Storrs, CT 06269-2155, USA. jduitama@engr.uconn.edu
authors.forename: Jorge
authors.initials: J
authors.lastname: Duitama
authors.forename: Justin
authors.initials: J
authors.lastname: Kennedy
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Dinakar
authors.forename: Yözen
authors.initials: Y
authors.lastname: Hernández
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wu
authors.forename: Ion I
authors.initials: II
authors.lastname: Măndoiu
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D005838:Genotype; D015810:Linkage Disequilibrium; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software