Online system for faster multipoint linkage analysis via parallel execution on thousands of personal computers - PubMed (original) (raw)

Online system for faster multipoint linkage analysis via parallel execution on thousands of personal computers

M Silberstein et al. Am J Hum Genet. 2006 Jun.

Abstract

Computation of LOD scores is a valuable tool for mapping disease-susceptibility genes in the study of Mendelian and complex diseases. However, computation of exact multipoint likelihoods of large inbred pedigrees with extensive missing data is often beyond the capabilities of a single computer. We present a distributed system called "SUPERLINK-ONLINE," for the computation of multipoint LOD scores of large inbred pedigrees. It achieves high performance via the efficient parallelization of the algorithms in SUPERLINK, a state-of-the-art serial program for these tasks, and through the use of the idle cycles of thousands of personal computers. The main algorithmic challenge has been to efficiently split a large task for distributed execution in a highly dynamic, nondedicated running environment. Notably, the system is available online, which allows computationally intensive analyses to be performed with no need for either the installation of software or the maintenance of a complicated distributed environment. As the system was being developed, it was extensively tested by collaborating medical centers worldwide on a variety of real data sets, some of which are presented in this article.

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Figures

Figure 1

A Bayesian network for three-point analysis

Figure 2

Pedigree reprinted from Knappskog et al.

Figure 3

Pedigree reprinted from Seboun et al.

Figure 4

Pedigree with 266 individuals (produced by OPediT)

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References

Web Resources

1. 1. OPediT, http://www.circusoft.com/content/product/5 (for drawings of the pedigree in experiment D)
2. 1. SUPERLINK-ONLINE, http://bioinfo.cs.technion.ac.il/superlink-online (for download, http://bioinfo.cs.technion.ac.il/superlink-online/download)

References

1. 1. Elston R, Stewart J (1971) A general model for the analysis of pedigree data. Hum Hered 21:523–542 - PubMed
2. 1. Lander E, Green P (1987) Construction of multilocus genetic maps in humans. Proc Natl Acad Sci 84:2363–2367 - PMC - PubMed
3. 1. Fishelson M, Geiger D (2004) Optimizing exact genetic linkage computations. J Comput Biol 11:263–27510.1089/1066527041410409 - DOI - PubMed
4. 1. Cottingham RW, Idury RM, Schäffer AA (1993) Faster sequential genetic linkage computations. Am J Hum Genet 53:252–263 - PMC - PubMed
5. 1. O’Connell J, Weeks D (1995) The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set-recoding and fuzzy inheritance. Nat Genet 11:402–40810.1038/ng1295-402 - DOI - PubMed

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