minimac is a low memory, computationally efficient implementation of the MaCH algorithm for genotype imputation. It is designed to work on phased genotypes and can handle very large reference panels with hundreds or thousands of haplotypes. The name has two parts. The first, "mini", refers to the modest amount of computational resources it requires. The second, "mac", is short hand for MaCH, our widely used algorithm for genotype imputation.
A good rule of thumb is that minimac should take about 1 hour to impute 1,000,000 markers in 1,000 individuals using a reference panel with 100 haplotypes. Performance should scale linearly with respect to all these factors. So, your approximate computing time in hours should be about:
These statistics refer to Intel X7460 CPU running at 2.66 GHz using 1 core and your mileage may vary; most modern CPUs should be no more than a few times faster (or slower) than that.
If you are estimating model parameters at the same time as imputing missing genotypes, you can account for the time needed for parameter estimation with the following formula:
In this updated formula, Nrounds represents the number of iterations used for parameter refinement and Nstates represents the maximum number of reference and target haplotypes considered for each update.
A public release of
minimac is expected here soon.
Beta-version available upon request (email@example.com or firstname.lastname@example.org)
Step 1: Pre-Phasing
For the pre-phasing step we recommend MaCH using the --phase command line option. As input MaCH needs a Merlin format pedigree and data file. All markers must be ordered according to their physical position.
Your Own Data
Within each file, markers should be stored by chromosome position. Alleles should be stored in the forward strand and can be encoded as 'A', 'C', 'G' or 'T' (there is no need to use numeric identifiers for each allele).
The 1000 Genome pilot project genotypes use NCBI Build 36.
mach1 -d sample.dat -p sample.ped --rounds 20 --states 200 --phase --interim 1 --sample 1 --compact
||Data file in Merlin format. Markers should be listed according to their order along the chromosome.|
||Pedigree file in Merlin format. Alleles should be labeled on the forward strand.|
||Number of haplotypes to consider during each update. Increasing this value will typically lead to better haplotypes, but can dramatically increase computing time and memory use. A value of 100 - 400 is typical.|
|| Iterations of the Markov sampler to use for haplotyping. Typically, using 20 - 100 rounds should give good results. To obtain better results, it is usually better to increase the |
||Request that intermediate results should be saved to disk periodically.|
||Tell MaCH to estimate phased haplotypes for each individual.|
||Reduce memory use at the cost of approximately doubling runtime. This option is recommended for most GWAS scale datasets and computing platforms.|
Step 2: Imputation
Imputing genotypes using minimac is an easy straightforward process: after selecting a set of reference haplotypes (see below how to get the latest 1000 Genomes reference panel ready to go with minimac ), plugging-in the target haplotypes from the pre-phasing step and setting the number of rounds to use for the model parameter estimation, samples get imputed once a second.
Reference haplotypes generated by the 1000 Genomes project and formatted so that they are ready for analysis are available from the MaCH download page. The most recent set of haplotypes were generated in June 2010 by combining genotype calls generated at the Broad, Sanger and the University of Michigan. In our hands, this June 2010 release is substantially better than previous 1000 Genome Project genotype call sets.
minimac --refHaps ref.hap.gz --refSnps ref.snps.gz --haps target.hap.gz --snps target.snps.gz
||List of SNPs in the reference panel|
||Reference haplotypes (e.g. from MaCH download page)|
||SNPs in phased haplotypes. These should largely be a subset of the SNPs in the reference panel.|
||Phased haplotypes where missing genotypes will be imputed.|
||Rounds of optimization for model parameters, which describe population recombination rates and per SNP error rates.|
||Maximum number of reference (or target) haplotypes to examined during parameter optimization.|
||Optionally, a string that is used to help generate output file names.|
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If you are looking for a low calorie version of the Big Mac sandwich, you'll be sad to know the Mini Mac has been discontinued. However, you are not the only one who likes the idea of a Mini Mac and you'll probably find some company on the web .