Highly scalable genotype phasing by entropy minimization

IEEE/ACM Trans Comput Biol Bioinform. 2008 Apr-Jun;5(2):252-61. doi: 10.1109/TCBB.2007.70223.


A Single Nucleotide Polymorphism (SNP) is a position in the genome at which two or more of the possible four nucleotides occur in a large percentage of the population. SNPs account for most of the genetic variability between individuals,and mapping SNPs in the human population has become the next high-priority in genomics after the completion of the Human Genome project. In diploid organisms such as humans, there are two non-identical copies of each autosomal chromosome. A description of the SNPs in a chromosome is called a haplotype. At present, it is prohibitively expensive to directly determine the haplotypes of an individual, but it is possible to obtain rather easily the conflated SNP information in the so called genotype. Computational methods for genotype phasing, i.e., inferring haplotypes from genotype data, have received much attention in recent years as haplotype information leads to increased statistical power of disease association tests. However, many of the existing algorithms have impractical running time for phasing large genotype data sets such as those generated by the international HapMap project. In this paper we propose a highly scalable algorithm based on entropy minimization. Our algorithm is capable of phasing both unrelated and related genotypes coming from complex pedigrees. Experimental results on both real and simulated datasets show that our algorithm achieves a phasing accuracy worse but close to that of best existing methods while being several orders of magnitude faster. The open source code implementation of the algorithm and a web interface are publicly available at http://dna.engr.uconn.edu/~software/ent/.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms*
  • Alleles
  • Computational Biology
  • Databases, Nucleic Acid
  • Female
  • Genetic Techniques
  • Genotype*
  • Humans
  • Male
  • Models, Genetic
  • Models, Statistical
  • Pedigree
  • Polymorphism, Single Nucleotide*