Changes

From Genome Analysis Wiki
Jump to: navigation, search

Minimac

9,761 bytes added, 12:53, 9 March 2018
no edit summary
'''You may want to learn about new and improved [[Minimac4]].'''
 
'''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.
There are several minimac related pages on this wiki. The major ones are: * [[Minimac]] - This page, the main minimac page.* [[Minimac: Tutorial]] - A short minimac tutorial.* [[Minimac: 1000 Genomes Imputation Cookbook]] - Cookbook instructions for 1000 Genomes Imputation with Minimac* [[Minimac Command Reference]] - Summary of minimac options* [[Minimac Diagnostics]] - Summary of diagnostics for imputation performance generated by minimac *[https://imputationserver.sph.umich.edu Imputation server] - We are running imputation (and pre-phasing) for you!   =Download =A binary Linux (64 bit) version of minimac is available [http://csg.sph.umich.edu/cfuchsb/minimac-beta-2013.7.17.tgz from here] and source code [http://csg.sph.umich.edu/cfuchsb/minimac.src.tgz from here] The current version of minimac should be stamped 2013.7.17 - if your version shows a different version number or date stamp when it runs, it is not current.  If you use this beta version, please be sure to stop by the [http://www.sph.umich.edu/csg/abecasis/MaCH/download/ MaCH download page] and fill out the registration form, so that we can let you know when an official release is available and keep you updated with respect to any bug fixes.  == Multiprocessor Version == The current version of minimac comes in two flavours, <code>minimac</code> and <code>minimac-omp</code>. The latter version uses the [[OpenMP]] protocol to support multi-threading, resulting in faster throughput. BE AWARE: since this version of minimac runs in parallel the order of samples in the output files (*dose, *haps,...) will vary between runs. Therefore, e.g. chunks have to be merged by sample id. == Change log == 2013.7.17 - minor bug fixes -- all variants (SNPs, InDels, SVs) in the reference VCF will be imputed - independent from the FILTER column setting - improved performance (Thanks to David Hinds - see also [[minimac2]] for the full set of performance improvements) 2012.11.16 - minor bug fixes 2012.10.9 - added: improved support for [http://www.shapeit.fr ShapeIT] phased haplotypes 2012.10.3 - added: full support for reference panel based chunking 2012.9.22 - fixed: chunk chromosome bug 2012.8.6 (early adopter) - added: chromosome X support 2012.3.14 - fixed: problem with --startposition  2012.2.29 - added: VCF support - added: IDR (Insertion, Deletion, Reference) support == Questions and Comments == Please contact [mailto:goncalo@umich.edu Goncalo Abecasis] or [mailto:cfuchsb@umich.edu Christian Fuchsberger]. = Performance = == Pre-phasing ==For the pre-phasing step, cost increases quadratically with the number of states and linearly with the number of rounds. The following table provides a simple example. {| class="wikitable" border="1" cellpadding="2"|- bgcolor="lightgray"! States! Cost per round|- | 100 states| 3 min|- | 200 states| 12 min = (3 min * 2<sup>2</sup>)|- | 400 states| 48 min = (3 min * 4<sup>2</sup>)|- | 500 states| 75 min = (3 min * 5<sup>2</sup>)|} So, in this case running haplotyping with 500 states and 10 rounds would require 75 min * 10 = 750 min. Typically, haplotype quality improves rapidly with the number of states but only slowly with the number of rounds. We recommend running ~20 rounds of the MaCH haplotyper and selecting a number of states as high as your patience will allow (but ideally greater than 200). == 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:
</math>
These statistics refer to a single core in a modern Intel X7460 CPU running at 2.66 GHz using 1 core and , although your mileage may will 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, N<sub>rounds</sub> represents the number of iterations used for parameter refinement and N<sub>states</sub> represents the maximum number of reference and target haplotypes considered for each update.
== Release Date =Getting Started =
A public release of <code>Using minimac</code> is expected here soonfor genotype imputation involves two steps.BetaFirst, you will have to estimate haplotypes for your entire sample -version available upon request (cfuchsb@umich- this will be the more computationally demanding step.edu or goncalo@umichOnce that is done, you will be ready to quickly impute missing genotypes using the reference panel of your choice.edu)
== Getting Started Estimating Haplotypes for Your Sample ==
=== Step 1: PreFor the haplotyping step, we current recommend using [[MaCH]] with the -Phasing ===-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.
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.=== Preparing Your Data ===
==== Your Own Data ====To get started, you will need to store your data in [[Merlin]] format pedigree and data files, one per chromosome. For details, of the Merlin file format, see the [http://csg.sph.umich.edu/abecasis/Merlin/tour/input_files.html Merlin Tutorial].
To get startedWithin each file, you will need to store your data markers should be stored by chromosome position. Alleles should be stored in [[Merlin]] format pedigree the forward strand and data filescan be encoded as 'A', one per chromosome. For details'C', of the Merlin file format, see the [http://www.sph.umich.edu/csg/abecasis/Merlin/tour/input_files.html Merlin Tutorial]'G' or 'T' (there is no need to use numeric identifiers for each allele).
Within each fileWe recommend that, if at all possible, markers you should be stored by chromosome 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 positionand strand for each marker seems like hard work, don't despair. Alleles For you, this should be stored in the forward strand and can be encoded as 'A'hardest bit of the entire process! For the computer, 'C', 'G' or 'T' (there the fun is no need about to use numeric identifiers for start. ==== NCBI build 36 / NCBI build 37 ====The 1000G June reference panel is on build 36, future 1000G reference panels will be on build 37. This has also some impact on the pre-phasing:some SNPs will ordered differently in each allelegenome build (we expect order will be more accurate in more recent builds!). Purists will claim that imputation using NCBI build 36 and NCBI build 37 reference panels requires phasing using the exact same reference panel -- others will claim this makes little difference. === Running MaCH ===
The 1000 Genome pilot project genotypes use NCBI Build 36.A typical MaCH command line to estimate phased haplotypes might look like this:
==== Usage ==== mach1 -d sample.dat -p sample.ped --rounds 20 --states 200 --phase --interim 1 5 --sample 1 5 --compact
==== Parameters ====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"
! Description
|-
|style=white-space:nowrap| <code>-d sample.dat</code>| Data file in [http://wwwcsg.sph.umich.edu/csg/abecasis/Merlin/tour/input_files.html Merlin format]. Markers should be listed according to their order along the chromosome.
|-
| <code>-p sample.ped</code>
| Pedigree file in [http://wwwcsg.sph.umich.edu/csg/abecasis/Merlin/tour/input_files.html Merlin format]. Alleles should be labeled on the forward strand.
|-
| <code>--states 200</code>
| 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 100 200 - 400 is typical.
|-
| <code>--rounds 5020</code>| Iterations of the Markov sampler to use for haplotyping. Typically, using 20 - 100 30 rounds should give good results. To obtain better results, it is usually better to increase the <code>--states</code> parameter.
|-
| <code>--interim 5</code>
| Request that intermediate results should be saved to disk periodically. These will facilitate analyses in case a run doesn't complete.|-| <code>--sample 5</code>| Request that random (but plausible) sets of haplotypes for each individual should be drawn every 5 iterations. This parameter is optional, but for some rare variant analyses, these alternative haplotypes can be very useful.
|-
| <code>--phase</code>
|}
=== Step 2: Imputation into Phased Haplotypes === Imputing genotypes using '''minimac''' is an easy and 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 previous step and setting the number of rounds to use for the model parameter estimation, samples get imputed once imputation should proceed rapidly. === Creating SNP List File === '''Minimac''' requires a file listing markers in the haplotype file. This file can be easily generated by extracting the secondcolumn from the .dat file.In a standard Unix system, a command like this should do:  cut -f 2 -d " " sample.dat > target.snps === Running Minimac ===
A typical minimac command line might look like this:
==== Reference Haplotypes using a VCF reference panel ==== minimac --vcfReference --refHaps ref.vcf.gz --haps target.hap.gz --snps target.snps.gz --rounds 5 --states 200 --prefix results
Reference haplotypes generated by the 1000 Genomes project and formatted so that they are ready for analysis are available from the [http'''Note'''://www.sph.umich.edu/csg/abecasis/MACH/download/1000GGWAS SNPs (file -2010-06snps target.html MaCH download page]snps. The most recent set of haplotypes were generated gz) are by default expected to be in June 2010 by combining genotype calls generated at the Broadchr:pos format e.g. 1:1000 and on build37/hg19; otherwise, Sanger and please set the University of Michigan. In our hands, this June 2010 release is substantially better than previous 1000 Genome Project genotype call sets.--rs flag
==== Usage using a MaCH reference panel ==== minimac --refHaps ref.hap.gz --refSnps ref.snps.gz --haps target.hap.gz --snps target.snps.gz
==== Parameters ==== minimac --refHaps ref.hap.gz --refSnps ref.snps.gz --haps target.hap.gz --snps target.snps.gz --rounds 5 --states 200 --prefix results A detailed description of all minimac options is available [[Minimac Command Reference|elsewhere]]. Here is a brief description of the above parameters:
{| class="wikitable" border="1" cellpadding="2"
! Description
|-
| <code>--refSnps ref.snps.gz </code>
| List of SNPs in the reference panel
|-
| <code>--refHaps ref.hap.gz </code> | Reference haplotypes (e.g. from [http://wwwcsg.sph.umich.edu/csg/abecasis/MACH/download/1000G-2010-06.html MaCH download page])
|-
| <code>--vcfReference </code> | This option specifies that the provided --refHaps file is provided in VCF format , no --refSNPs file needed.|- | <code>--rs </code> | In combination with --vcfReference, allows to use rs GWAS SNP identifiers|- | <code>--snps target.snps.gz </code>
| SNPs in phased haplotypes. These should largely be a subset of the SNPs in the reference panel.
|-
| <code>--haps target.hap.gz </code>
| Phased haplotypes where missing genotypes will be imputed.
|-
| <code>--sample target.sample </code>
| Sample list in ShapeIT format.
|-
| <code>--shape_haps target.hap.gz </code>
| ShapeIT phased haplotypes where missing genotypes will be imputed.
|-
| <code>--chr 22</code>
| Chromosome for which we will carry out imputation (needed to run ShapeIT with chr:pos identifiers - default setting).
|-
| <code>--rounds 5</code>
|-
| <code>--states 200</code>
| Maximum number of reference (or target) haplotypes to be examined during parameter optimization.
|-
| <code>--prefix imputed</code>
|}
=== Reference Haplotypes === Reference haplotypes generated by the 1000 Genomes project and formatted so that they are ready for analysis are available from the [http://csg.sph.umich.edu/abecasis/MACH/download/ MaCH download page]. As of this writing, the most recent set of haplotypes are based on genotype calls were generated in May 2011 and are an interim analysis of Project's Phase I data. === Imputation quality evaluation ===To evaluate imputation quality, Minimac hides data for each genotyped SNP in turn and calculates 3 statistics:* looRSQ - this is the estimated rsq for that SNP (as if SNP weren't typed). * empR - this is the empirical correlation between true and imputed genotypes for the SNP. If this is negative, the SNP is probably flipped. * empRSQ - this is the actual R2 value, comparing imputed and true genotypes.  These statistics can be found in the .info file === Additional Sources of Information === If the combination of MaCH and Minimac still runs too slowly for you, and you have access to a multi-processor compute cluster, you can look at [[ChunkChromosome]] page to learn how to conveniently split each chromosome into multiple segments that can be analyzed in parallel. For information on how to put the resulting chunks back together, see [[Ligate Minimac|this page]]. If you are especially interested in 1000 Genomes Imputation, then you should look at the [[Minimac: 1000 Genomes Imputation Cookbook]]. == X Chromosome Imputation ==minimac supports the imputation of genotypes on the X chromosome (non-pseudo-autosomal part). # Split the X chromosome pedigree file by sex.## For females: follow the same protocol as for autosomes (phase with MaCH and impute with minimac).## For males### Remove the pseudo-autosomal part (for build hg18: chrX:1-2709520 and chrX:154584238-154913754 ; for build hg19 chrX:60001-2699520 and chrX:154931044-155260560)### Convert the pedigree file into a MaCH haplotype file (missing genotypes should be encoded as: "0" or "." or "N" ) and impute using minimac as described above.   :::: '''<Example of a male only pedigree file>''':::: FAM1003 ID1234 0 0 M A/A A/A C/C:::: FAM1004 ID5678 0 0 M 0/0 C/0 G/G:::: ...:::: '''<End of pedigree file>''' :::: ''Note that, consistent with the Merlin convention, hemizygous males are listed as if they were homozygous.'' :::: '''<Example of the corresponding haplotype file>''':::: FAM1003->ID1234 HAPLO1 AAC:::: FAM1003->ID1234 HAPLO2 AAC:::: FAM1004->ID5678 HAPLO1 0CG:::: FAM1004->ID5678 HAPLO2 0CG:::: ...:::: '''<End of the corresponding haplotype file>''' = Post-imputation Association Analysis === Quantitative Traits ==Please use [http://csg.sph.umich.edu/yli/mach/download/mach2qtl.source.V108.tgz mach2qtl]. == Binary Traits ==Please use [http://csg.sph.umich.edu/yli/mach/download/mach2dat.source.1.0.18.tgz mach2dat]. Versions 1.0.18 and above accommodate to minimac output. = Reference = If you use [[minimac]] or [[minimac2]] please cite:  Fuchsberger C, Abecasis GR, Hinds DA. minimac2: faster genotype imputation. Bioinformatics 2014 [http://bioinformatics.oxfordjournals.org/content/early/2014/10/22/bioinformatics.btu704.short] Howie B, Fuchsberger C, Stephens M, Marchini J, and Abecasis GR.Fast and accurate genotype imputation in genome-wide association studiesthrough pre-phasing. Nature Genetics 2012 [http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2354.html] = Questions and Comments = Please contact [mailto:goncalo@umich.edu Goncalo Abecasis] or [mailto:cfuchsb@umich.edu Christian Fuchsberger]. = Related Pages ==
If you are looking to learn about small computers made by Apple, Inc., you have come to the wrong page. Try looking at http://www.apple.com/macmini/, instead.
487
edits

Navigation menu