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== Getting Started ==
== Getting Started ==
Using minimac for genotype imputation involves two steps. First, you will have to estimate haplotypes for your entire sample -- this will be the more computationally demanding step. Once that is done, you will be ready to quickly impute missing genotypes using the reference panel of your choice.
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.
=== Estimating Haplotypes for Your Sample ===
For the haplotyping step, we current recommend using [[MaCH]] with the --phase command line option. As input [[MaCH]] will need [[Merlin]] format pedigree and data files. All markers should be ordered according to their physical position and alleles should be labeled on the forward strand.
==== Your Own Data ====
==== 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).
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).
We recommend that, if at all possible, you should phase your chromosomes according to NCBI build 37. Future releases of the 1000 Genomes Reference panel and other public sets of reference haplotypes are expected to use this genome build.
If figuring out position and strand for each marker seems like hard work, don't despair. For you, this should be the hardest bit of the entire process! For the computer, the fun is about to start.
==== Parameters ====
==== Running MaCH ====
A typical MaCH command line to estimate phased haplotypes might look like this:
mach1 -d sample.dat -p sample.ped --rounds 20 --states 200 --phase --interim 5 --compact
This will request that MaCH estimate haplotypes for your sample, using 20 iterations of its Markov sampler and conditioning each update on up to 200 haplotypes. A summary description of these parameters follows (but for a more complete description, you should go to the MaCH website):
{| class="wikitable" border="1" cellpadding="2"
{| class="wikitable" border="1" cellpadding="2"
| 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.
| 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.
|-
|-
| <code>--rounds 50</code>
| <code>--rounds 20</code>
| 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 <code>--states</code> parameter.
| 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 <code>--states</code> parameter.
|-
|-
| <code>--interim 5</code>
| <code>--interim 5</code>
| Request that intermediate results should be saved to disk periodically.
| Request that intermediate results should be saved to disk periodically. These will facilitate analyses in case a run doesn't complete.
|-
|-
| <code>--phase</code>
| <code>--phase</code>
|}
|}
=== Step 2: Imputation ===
=== Imputation into Phased Haplotypes ===
Imputing genotypes using '''minimac''' is an easy straightforward process: after selecting a set of reference haplotypes, plugging-in the target haplotypes from the previous step and setting the number of rounds to use for the model parameter estimation, imputation should proceed rapidly.
==== Reference Haplotypes ====
==== Running Minimac ====
A typical minimac command line might look like this:
minimac --refHaps ref.hap.gz --refSnps ref.snps.gz --haps target.hap.gz --snps target.snps.gz --rounds 5 --states 200 --prefix results
minimac --refHaps ref.hap.gz --refSnps ref.snps.gz --haps target.hap.gz --snps target.snps.gz
A detailed description of all minimac options is available [[Minimac|elsewhere]]. Here is a brief description of the above parameters:
{| class="wikitable" border="1" cellpadding="2"
{| class="wikitable" border="1" cellpadding="2"
| Optionally, a string that is used to help generate output file names.
| Optionally, a string that is used to help generate output file names.
|}
|}
==== Reference Haplotypes ====
Reference haplotypes generated by the 1000 Genomes project and formatted so that they are ready for analysis are available from the [http://www.sph.umich.edu/csg/abecasis/MACH/download/1000G-2010-06.html 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.
== Related Pages ==
== Related Pages ==
