Genome Analysis Wiki - User contributions [en]

Minimac4

2019-07-20T03:29:04Z

Yukt:

= Introduction =

'''Minimac4 ''' is a latest version in the series of genotype imputation software - preceded by [[Minimac3|Minimac3]] (2015), [[Minimac2|Minimac2]] (2014), [[Minimac|minimac]] (2012) and [[MaCH|MaCH]] (2010). '''Minimac4''' is a lower memory and more computationally efficient implementation of the original algorithms with comparable imputation quality.

The Minimac3 mailing list has been renamed as the Minimac4 mailing list. If you were already a member, no need to re-join. If not, please join our [https://groups.google.com/forum/embed/?place=forum/minimac4-help&umich.edu| mailing list] to get updates about future releases or report possible bugs or email them to [mailto:yukt@umich.edu Ketian Yu] or [mailto:sayantan@umich.edu Sayantan Das].'''

= Installation =

'''Minimac4 (version 1.0.0, released 2.14.2018)''' is currently available on [https://github.com/Santy-8128/Minimac4 Minimac4 Github].

The easiest way to install Minimac4 and its dependencies is to use the install.sh file provided.
git clone <nowiki>https://github.com/statgen/Minimac4.git</nowiki>
cd Minimac4
bash install.sh

Please see [https://github.com/Santy-8128/Minimac4 Minimac4 Github] for the full instructions for installation.

Commonly used reference panels in M3VCF format are available for download in [[#Reference Panels for Download | Reference Panels]].

= What's New =

The input file format, output file formats and typical command lines are the same in Minimac4 (as they were in minimac3). Some of the main new features are summarized below:

* '''Improved Speed - ''' Minimac4 is approximately '''6 times''' faster for 1000 Genomes Phase 1 and Phase 3 and '''2 times''' faster for the HRC reference panels at comparable accuracy (details of accuracy for imputing into 10 European samples are given here). The speed can be further improved by tuning the approximation parameters (see below), but we recommend using the default values.

* '''Automated Chunking - ''' Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back. This caps the memory usage across different chromosomes (memory requirement is based on chunk size, not chromosome size). The length of the chunk and the overlap can be controlled by the <code>--chunkLengthMb</code> and <code>--chunkLengthOverlapMb</code> options, although we recommend using the default values of 20 and 3, respectively.

* '''Approximations - ''' Minimac4 uses some simple approximations to speed up the imputation analyses. The levels of approximation can be controlled by the parameters <code>--probThreshold</code>, <code>--diffThreshold</code>, and <code>--topThreshold</code> (details given in Minimac4 Usage). Higher levels of approximation will reduce the compute time but marginally reduce the imputation accuracy. We recommend using the default values (0.01).

* '''Improved Chromosome X/Y Support - ''' Minimac4 can handle different ploidys in the same VCF file for imputation of sex chromosomes. For example, for the non-PAR region on chromosome X, males and females can be imputed together, irrespective of whether males are coded as haploids or diploids. However, each sample must have a fixed ploidy. Thus, PAR and non-PAR regions still need to be imputed separately. Please see Chromosome X Imputation for more details.

* '''Other Helpful Features'''
** We introduced a new feature called <code>--memUsage</code> that will estimate and report the memory required by Minimac4. This feature should be useful for users running their jobs on a compute cluster that requires memory specification.
** We introduced some other FORMAT options for the output dosage data, allowing users to retrieve haplotype dosages, genotype probabilities, genotype dosages or any other measure of summary that they want.
** We have fixed the bug related to FILTER=GENOTYPED and FILTER=GENOTYPED_ONLY which was causing a crash in bcftools.

* '''Obsolete Features'''
** In Minimac4, we removed the <code>--doseOutput</code> and <code>--hapOutput</code> options. Please use [[DosageConvertor]] to convert your files to MaCH or PLINK dosage format.
** Currently Minimac4 can ONLY handle M3VCF format files. If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4. The same holds for the option <code>--processReference</code> as well. Although the handle is made available, we will implement it in a later version.
** Parameters such as <code>--rounds</code>, <code>--states</code>, <code>--rec</code>, <code>--err</code> have been deactivated for now until we implement parameter estimation in minimac4.

= Usage =
A typical Minimac4 command line for imputation is as follows

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun

Here refPanel.m3vcf is the reference panel used in M3VCF format (e.g. 1000 Genomes), targetStudy.vcf is the phased GWAS data in VCF format, and testRun is the prefix for the output files.

=== Full List of Options ===
Please see '''[[Minimac4 Documentation]]''' for detailed explanation of all available options.

Also, users can always type the following for the full list of available options:
minimac4 --help

=== Convert VCF to M3VCF ===
If the reference panel is in VCF format, please use [[Minimac3]] to convert it into M3VCF format first.
../bin/Minimac3 --refHaps refPanel.vcf \
--processReference \
--prefix refPanel

=== Multi-Threading ===
The following example shows the same analysis as above, but using 5 threads:

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun \
--cpus 5

= Reference Panels for Download =

Some commonly used reference panels are available for download here:

{| class="wikitable" style="text-align:center" border="1" cellpadding="2"
|- bgcolor="lightgray"
! width="150px" |Reference Panel
! width="100px" |Number of Samples
! width="100px" |File Format
! width="100px" |Parameter Estimates Available
! width="120px" |Chromosomes
! width="80px" |Link
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 3''' 
(version 5)
| rowspan=4 style="text-align:center" | '''2,504'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_VCF_Files.tar.gz Download] 
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download] 
|-
|NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_NO_ESTIMATES.tar.gz Download] 
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 1''' 
(version 3)
| rowspan=4 | '''1,092'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_VCF_Files.tar.gz Download]
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download]
|-
| NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_NO_ESTIMATES.tar.gz Download]
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|}

= Useful Wiki Pages =

There are a few pages in this Wiki that may be useful to for '''Minimac4''' users. Here are links to a few:

* [[Minimac4| Minimac4 Overview Page]]

* [[Minimac4 Documentation]]

* [[M3VCF Files| M3VCF Files]]

Minimac4

2019-07-20T03:22:21Z

Yukt: /* Full List of Options */

= Introduction =

'''Minimac4 ''' is a latest version in the series of genotype imputation software - preceded by [[Minimac3|Minimac3]] (2015), [[Minimac2|Minimac2]] (2014), [[Minimac|minimac]] (2012) and [[MaCH|MaCH]] (2010). '''Minimac4''' is a lower memory and more computationally efficient implementation of the original algorithms with comparable imputation quality.

The Minimac3 mailing list has been renamed as the Minimac4 mailing list. If you were already a member, no need to re-join. If not, please join our [https://groups.google.com/forum/embed/?place=forum/minimac4-help&umich.edu| mailing list] to get updates about future releases or report possible bugs or email them to [mailto:yukt@umich.edu Ketian Yu] or [mailto:sayantan@umich.edu Sayantan Das].'''

= Download =

'''Minimac4 (version 1.0.0, released 2.14.2018)''' is currently available on [https://github.com/Santy-8128/Minimac4 Minimac4 Github]. Please follow the instructions in the GitHub repository for installation.

Commonly used reference panels in M3VCF format are available for download in [[#Reference Panels for Download | Reference Panels]].

= What's New =

The input file format, output file formats and typical command lines are the same in Minimac4 (as they were in minimac3). Some of the main new features are summarized below:

* '''Improved Speed - ''' Minimac4 is approximately '''6 times''' faster for 1000 Genomes Phase 1 and Phase 3 and '''2 times''' faster for the HRC reference panels at comparable accuracy (details of accuracy for imputing into 10 European samples are given here). The speed can be further improved by tuning the approximation parameters (see below), but we recommend using the default values.

* '''Automated Chunking - ''' Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back. This caps the memory usage across different chromosomes (memory requirement is based on chunk size, not chromosome size). The length of the chunk and the overlap can be controlled by the <code>--chunkLengthMb</code> and <code>--chunkLengthOverlapMb</code> options, although we recommend using the default values of 20 and 3, respectively.

* '''Approximations - ''' Minimac4 uses some simple approximations to speed up the imputation analyses. The levels of approximation can be controlled by the parameters <code>--probThreshold</code>, <code>--diffThreshold</code>, and <code>--topThreshold</code> (details given in Minimac4 Usage). Higher levels of approximation will reduce the compute time but marginally reduce the imputation accuracy. We recommend using the default values (0.01).

* '''Improved Chromosome X/Y Support - ''' Minimac4 can handle different ploidys in the same VCF file for imputation of sex chromosomes. For example, for the non-PAR region on chromosome X, males and females can be imputed together, irrespective of whether males are coded as haploids or diploids. However, each sample must have a fixed ploidy. Thus, PAR and non-PAR regions still need to be imputed separately. Please see Chromosome X Imputation for more details.

* '''Other Helpful Features'''
** We introduced a new feature called <code>--memUsage</code> that will estimate and report the memory required by Minimac4. This feature should be useful for users running their jobs on a compute cluster that requires memory specification.
** We introduced some other FORMAT options for the output dosage data, allowing users to retrieve haplotype dosages, genotype probabilities, genotype dosages or any other measure of summary that they want.
** We have fixed the bug related to FILTER=GENOTYPED and FILTER=GENOTYPED_ONLY which was causing a crash in bcftools.

* '''Obsolete Features'''
** In Minimac4, we removed the <code>--doseOutput</code> and <code>--hapOutput</code> options. Please use [[DosageConvertor]] to convert your files to MaCH or PLINK dosage format.
** Currently Minimac4 can ONLY handle M3VCF format files. If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4. The same holds for the option <code>--processReference</code> as well. Although the handle is made available, we will implement it in a later version.
** Parameters such as <code>--rounds</code>, <code>--states</code>, <code>--rec</code>, <code>--err</code> have been deactivated for now until we implement parameter estimation in minimac4.

= Usage =
The easiest way to install Minimac4 and its dependencies is to use the install.sh file provided.
git clone <nowiki>https://github.com/statgen/Minimac4.git</nowiki>
cd Minimac4
bash install.sh

A typical Minimac4 command line for imputation is as follows

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun

Here refPanel.m3vcf is the reference panel used in M3VCF format (e.g. 1000 Genomes), targetStudy.vcf is the phased GWAS data in VCF format, and testRun is the prefix for the output files.

=== Full List of Options ===
Please see '''[[Minimac4 Documentation]]''' for detailed explanation of all available options.

Also, users can always type the following for the full list of available options:
minimac4 --help

=== Convert VCF to M3VCF ===
If the reference panel is in VCF format, please use [[Minimac3]] to convert it into M3VCF format first.
../bin/Minimac3 --refHaps refPanel.vcf \
--processReference \
--prefix refPanel

=== Multi-Threading ===
The following example shows the same analysis as above, but using 5 threads:

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun \
--cpus 5

= Reference Panels for Download =

Some commonly used reference panels are available for download here:

{| class="wikitable" style="text-align:center" border="1" cellpadding="2"
|- bgcolor="lightgray"
! width="150px" |Reference Panel
! width="100px" |Number of Samples
! width="100px" |File Format
! width="100px" |Parameter Estimates Available
! width="120px" |Chromosomes
! width="80px" |Link
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 3''' 
(version 5)
| rowspan=4 style="text-align:center" | '''2,504'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_VCF_Files.tar.gz Download] 
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download] 
|-
|NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_NO_ESTIMATES.tar.gz Download] 
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 1''' 
(version 3)
| rowspan=4 | '''1,092'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_VCF_Files.tar.gz Download]
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download]
|-
| NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_NO_ESTIMATES.tar.gz Download]
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|}

= Useful Wiki Pages =

There are a few pages in this Wiki that may be useful to for '''Minimac4''' users. Here are links to a few:

* [[Minimac4| Minimac4 Overview Page]]

* [[Minimac4 Documentation]]

* [[M3VCF Files| M3VCF Files]]

Minimac4 Documentation

2019-07-20T03:17:05Z

Yukt:

A typical Minimac4 command line would have the following parameter options:

Reference Haplotypes : --refHaps [], --passOnly, --rsid,
--referenceEstimates [ON],
--mapFile [docs/geneticMapFile.b38.map.txt.gz]
Target Haplotypes : --haps []
Output Parameters : --prefix [Minimac4.Output], --estimate,
--nobgzip, --vcfBuffer [200], --format [GT,DS],
--allTypedSites, --meta, --memUsage
Chunking Parameters : --ChunkLengthMb [20.00], --ChunkOverlapMb [3.00]
Subset Parameters : --chr [], --start, --end, --window
Approximation Parameters : --minimac3, --probThreshold [0.01],
--diffThreshold [0.01], --topThreshold [0.01]
Other Parameters : --log, --help, --cpus [1], --params
PhoneHome : --noPhoneHome, --phoneHomeThinning [50]

Among all, '''--refHaps''' and '''--haps''' are required.

== Reference Haplotypes ==
;--refHaps <input_m3vcf_filename>
: This option defines the reference panel in M3VCF format to impute against.
: If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4.

; --passOnly
: DEACTIVATED for now. OFF by default. If ON, only variants will FILTER=PASS will be recorded from reference VCF file (does NOT work on M3VCF files yet).

;--rsid
: OFF by default. If ON, Minimac4 will only import RS ID of variants from ID column of reference file (if available).

;--referenceEstimates
: ON by default. If ON, Minimac4 expects the input M3VCF file comes with parameter estimate; otherwise, a genetic map file for option <code>--mapFile</code> is required.

;--mapFile <input_genetic_map_file>
: This option is automatically ignored except when <code>--referenceEstimates</code> is OFF.
: It defines the genetic map file used for recombination rate estimation during imputation.
: The input genetic map file should be tab-separated, with the first row as its header, and the columns representing chromosome id, base pair position, cumulative recombination rate in cM/Mb, and genetic map coordinates in cM, respectively.

== Target Haplotypes ==
;--haps <input_vcf_filename>
: This option defines the pre-phased target genotype data in VCF format to impute.

== Output Parameters ==
; --prefix <output_prefix>
: This option defines the output filename prefix for all files generated by Minimac4.
: If this option is omitted, all output files will have the prefix "Minimac4.Output" in the current working directory.

; --estimate
: DEACTIVATED for now. This option is equivalent to the option <code>--processReference</code> in [[Minimac3 Usage|Minimac3]].

; --nobgzip
: OFF by default. If ON, output files will be NOT bgzipped.

; --vcfBuffer
: This option defines the maximum number of samples in the target genotype data to be imputed at a time. By default, it is set as 200, or the total number of samples, whichever is smaller.
: Note that the larger the value is, the more memory Minimac4 will consume.

; --format
: This option specifies which fields to output for the FORMAT field in output imputed VCF file. Available handles are <code>GT</code>,<code>DS</code>,<code>HDS</code>,<code>GP</code>,<code>SD</code>. Default setting is <code>GT,DS</code>.
:* '''GT''' - Estimated most likely genotype.
:* '''DS''' - Estimated alternate allele dosage [P(0/1)+2*P(1/1)].
:* '''HDS''' - Estimated phased haploid alternate allele dosage.
:* '''GP''' - Estimated Posterior Genotype Probabilities P(0/0), P(0/1) and P(1/1).
:* '''SD''' - Estimated Variance of Posterior Genotype Probabilities.

;--allTypedSites
: OFF by default. If ON, Minimac4 will also include variants that were genotyped but NOT in the reference panel in the output files (and imputes any missing data in such variants to the major allele frequency).

;--meta
: OFF by default. If ON, Minimac4 will generate a separate file that can be used by [[MetaMinimac2|MetaMinimac2]] for meta-imputation.

;--memUsage
: OFF by default. If ON, Minimac4 will not perform imputation. Instead, it will estimate memory that imputation would consume based on a single chunk.

== Chunking Parameters ==
Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back.

;--ChunkLengthMb <float_number>
: This option defines the average length of chunks in units of million base pairs (Mb). The input value should be within (0.001, 300]. The default setting is 20.

;--ChunkOverlapMb <float_number>
: This option defines the length of overlap between chunks in units of Mb, 3Mb by default. The valid input value should be within (0.001, 300].
: The overlap length should be at most 1/3 of the chunk length, if larger, Minimac4 will automatically reduce it to 1/3 of the chunk length.

== Subset Parameters ==
The subset parameters are required if the user wishes to impute into a particular region of the chromosome rather than the whole chromosome (typically used when running imputation in chunks). If using the subset parameters, a default window of additional 500 Kbp is applied on either side as the buffer region, unless otherwise specified by the user. Variants from the buffer region are only used for imputation and not reported in the final output.
For example, to analyze chromosome 6 from position 1000000 to position 2000000 with 300000 base positions on either side as a buffer, one must use <code>--chr 6 --from 1000000 --to 2000000 --window 300000</code>.

; --chr <chromosome>
: This option specifies the chromosome number for which we will carry out imputation.
: Note that it is required to specify non-zero values for <code>--start</code> and <code>--end</code> when <code>--chr</code> option is used.

; --start <integer>
: This option specifies the start position of the region to be analyzed. Would not work without <code>--chr</code> option.

; --end <integer>
: This option specifies the end position of the region to be analyzed. Would not work without <code>--chr</code> option.

; --window <integer>
: This option specifies the length of buffer region in units of base pairs on either side of the region to be analyzed. Would not work without <code>--chr</code> option; otherwise, it is set as 500000 by default.

== Approximation Parameters ==
;--minimac3
: OFF by default. If ON, Minimac3 algorithm will be used for imputation.

;--probThreshold <float_number>

;--diffThreshold <float_number>

;--topThreshold <float_number>

== Other Parameters ==
; --log
: OFF by default. If ON, information including warnings and errors will be saved into <output_prefix>.logfile, instead printed on the screen.

; --help
: If ON, it will show the list of all available options.

;--cpus <integer>
: This option defines the number of cpus for parallel computing, 1 by default.

== PhoneHome ==
This option (by default) sends a message to a University of Michigan database about the success/failure of the analysis run (and as to what kind of failure had occurred, if so). No information about the data, file or file-name is sent back. User should use the handle <code>--noPhoneHome</code> to opt out from this option or should use <code>--phoneHomeThinning 50</code> to send back a message with 50% chance (typically used when running lots of command lines).

;--noPhoneHome
: OFF by default. If ON, code will NOT send a SUCCESS/FAILURE status of the execution to home server.

;--phoneHomeThinning <integer>
: Percentage probability of sending SUCCESS/FAILURE status of the execution to home server, 50 by default.

[[Minimac4| Back to Minimac4 Overview Page]]

Minimac4

2019-07-20T03:14:56Z

Yukt: /* Usage */

= Introduction =

'''Minimac4 ''' is a latest version in the series of genotype imputation software - preceded by [[Minimac3|Minimac3]] (2015), [[Minimac2|Minimac2]] (2014), [[Minimac|minimac]] (2012) and [[MaCH|MaCH]] (2010). '''Minimac4''' is a lower memory and more computationally efficient implementation of the original algorithms with comparable imputation quality.

The Minimac3 mailing list has been renamed as the Minimac4 mailing list. If you were already a member, no need to re-join. If not, please join our [https://groups.google.com/forum/embed/?place=forum/minimac4-help&umich.edu| mailing list] to get updates about future releases or report possible bugs or email them to [mailto:yukt@umich.edu Ketian Yu] or [mailto:sayantan@umich.edu Sayantan Das].'''

= Download =

'''Minimac4 (version 1.0.0, released 2.14.2018)''' is currently available on [https://github.com/Santy-8128/Minimac4 Minimac4 Github]. Please follow the instructions in the GitHub repository for installation.

Commonly used reference panels in M3VCF format are available for download in [[#Reference Panels for Download | Reference Panels]].

= What's New =

The input file format, output file formats and typical command lines are the same in Minimac4 (as they were in minimac3). Some of the main new features are summarized below:

* '''Improved Speed - ''' Minimac4 is approximately '''6 times''' faster for 1000 Genomes Phase 1 and Phase 3 and '''2 times''' faster for the HRC reference panels at comparable accuracy (details of accuracy for imputing into 10 European samples are given here). The speed can be further improved by tuning the approximation parameters (see below), but we recommend using the default values.

* '''Automated Chunking - ''' Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back. This caps the memory usage across different chromosomes (memory requirement is based on chunk size, not chromosome size). The length of the chunk and the overlap can be controlled by the <code>--chunkLengthMb</code> and <code>--chunkLengthOverlapMb</code> options, although we recommend using the default values of 20 and 3, respectively.

* '''Approximations - ''' Minimac4 uses some simple approximations to speed up the imputation analyses. The levels of approximation can be controlled by the parameters <code>--probThreshold</code>, <code>--diffThreshold</code>, and <code>--topThreshold</code> (details given in Minimac4 Usage). Higher levels of approximation will reduce the compute time but marginally reduce the imputation accuracy. We recommend using the default values (0.01).

* '''Improved Chromosome X/Y Support - ''' Minimac4 can handle different ploidys in the same VCF file for imputation of sex chromosomes. For example, for the non-PAR region on chromosome X, males and females can be imputed together, irrespective of whether males are coded as haploids or diploids. However, each sample must have a fixed ploidy. Thus, PAR and non-PAR regions still need to be imputed separately. Please see Chromosome X Imputation for more details.

* '''Other Helpful Features'''
** We introduced a new feature called <code>--memUsage</code> that will estimate and report the memory required by Minimac4. This feature should be useful for users running their jobs on a compute cluster that requires memory specification.
** We introduced some other FORMAT options for the output dosage data, allowing users to retrieve haplotype dosages, genotype probabilities, genotype dosages or any other measure of summary that they want.
** We have fixed the bug related to FILTER=GENOTYPED and FILTER=GENOTYPED_ONLY which was causing a crash in bcftools.

* '''Obsolete Features'''
** In Minimac4, we removed the <code>--doseOutput</code> and <code>--hapOutput</code> options. Please use [[DosageConvertor]] to convert your files to MaCH or PLINK dosage format.
** Currently Minimac4 can ONLY handle M3VCF format files. If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4. The same holds for the option <code>--processReference</code> as well. Although the handle is made available, we will implement it in a later version.
** Parameters such as <code>--rounds</code>, <code>--states</code>, <code>--rec</code>, <code>--err</code> have been deactivated for now until we implement parameter estimation in minimac4.

= Usage =
The easiest way to install Minimac4 and its dependencies is to use the install.sh file provided.
git clone <nowiki>https://github.com/statgen/Minimac4.git</nowiki>
cd Minimac4
bash install.sh

A typical Minimac4 command line for imputation is as follows

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun

Here refPanel.m3vcf is the reference panel used in M3VCF format (e.g. 1000 Genomes), targetStudy.vcf is the phased GWAS data in VCF format, and testRun is the prefix for the output files.

=== Full List of Options ===
Users can always type the following for further support:
minimac4 --help

'''Please see [[Minimac4 Documentation | Minimac4 Documentation]] for detailed explanation of all available options.'''

=== Convert VCF to M3VCF ===
If the reference panel is in VCF format, please use [[Minimac3]] to convert it into M3VCF format first.
../bin/Minimac3 --refHaps refPanel.vcf \
--processReference \
--prefix refPanel

=== Multi-Threading ===
The following example shows the same analysis as above, but using 5 threads:

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun \
--cpus 5

= Reference Panels for Download =

Some commonly used reference panels are available for download here:

{| class="wikitable" style="text-align:center" border="1" cellpadding="2"
|- bgcolor="lightgray"
! width="150px" |Reference Panel
! width="100px" |Number of Samples
! width="100px" |File Format
! width="100px" |Parameter Estimates Available
! width="120px" |Chromosomes
! width="80px" |Link
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 3''' 
(version 5)
| rowspan=4 style="text-align:center" | '''2,504'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_VCF_Files.tar.gz Download] 
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download] 
|-
|NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_NO_ESTIMATES.tar.gz Download] 
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 1''' 
(version 3)
| rowspan=4 | '''1,092'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_VCF_Files.tar.gz Download]
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download]
|-
| NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_NO_ESTIMATES.tar.gz Download]
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|}

= Useful Wiki Pages =

There are a few pages in this Wiki that may be useful to for '''Minimac4''' users. Here are links to a few:

* [[Minimac4| Minimac4 Overview Page]]

* [[Minimac4 Documentation]]

* [[M3VCF Files| M3VCF Files]]

Minimac4

2019-07-20T03:13:58Z

Yukt:

= Introduction =

'''Minimac4 ''' is a latest version in the series of genotype imputation software - preceded by [[Minimac3|Minimac3]] (2015), [[Minimac2|Minimac2]] (2014), [[Minimac|minimac]] (2012) and [[MaCH|MaCH]] (2010). '''Minimac4''' is a lower memory and more computationally efficient implementation of the original algorithms with comparable imputation quality.

The Minimac3 mailing list has been renamed as the Minimac4 mailing list. If you were already a member, no need to re-join. If not, please join our [https://groups.google.com/forum/embed/?place=forum/minimac4-help&umich.edu| mailing list] to get updates about future releases or report possible bugs or email them to [mailto:yukt@umich.edu Ketian Yu] or [mailto:sayantan@umich.edu Sayantan Das].'''

= Download =

'''Minimac4 (version 1.0.0, released 2.14.2018)''' is currently available on [https://github.com/Santy-8128/Minimac4 Minimac4 Github]. Please follow the instructions in the GitHub repository for installation.

Commonly used reference panels in M3VCF format are available for download in [[#Reference Panels for Download | Reference Panels]].

= What's New =

The input file format, output file formats and typical command lines are the same in Minimac4 (as they were in minimac3). Some of the main new features are summarized below:

* '''Improved Speed - ''' Minimac4 is approximately '''6 times''' faster for 1000 Genomes Phase 1 and Phase 3 and '''2 times''' faster for the HRC reference panels at comparable accuracy (details of accuracy for imputing into 10 European samples are given here). The speed can be further improved by tuning the approximation parameters (see below), but we recommend using the default values.

* '''Automated Chunking - ''' Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back. This caps the memory usage across different chromosomes (memory requirement is based on chunk size, not chromosome size). The length of the chunk and the overlap can be controlled by the <code>--chunkLengthMb</code> and <code>--chunkLengthOverlapMb</code> options, although we recommend using the default values of 20 and 3, respectively.

* '''Approximations - ''' Minimac4 uses some simple approximations to speed up the imputation analyses. The levels of approximation can be controlled by the parameters <code>--probThreshold</code>, <code>--diffThreshold</code>, and <code>--topThreshold</code> (details given in Minimac4 Usage). Higher levels of approximation will reduce the compute time but marginally reduce the imputation accuracy. We recommend using the default values (0.01).

* '''Improved Chromosome X/Y Support - ''' Minimac4 can handle different ploidys in the same VCF file for imputation of sex chromosomes. For example, for the non-PAR region on chromosome X, males and females can be imputed together, irrespective of whether males are coded as haploids or diploids. However, each sample must have a fixed ploidy. Thus, PAR and non-PAR regions still need to be imputed separately. Please see Chromosome X Imputation for more details.

* '''Other Helpful Features'''
** We introduced a new feature called <code>--memUsage</code> that will estimate and report the memory required by Minimac4. This feature should be useful for users running their jobs on a compute cluster that requires memory specification.
** We introduced some other FORMAT options for the output dosage data, allowing users to retrieve haplotype dosages, genotype probabilities, genotype dosages or any other measure of summary that they want.
** We have fixed the bug related to FILTER=GENOTYPED and FILTER=GENOTYPED_ONLY which was causing a crash in bcftools.

* '''Obsolete Features'''
** In Minimac4, we removed the <code>--doseOutput</code> and <code>--hapOutput</code> options. Please use [[DosageConvertor]] to convert your files to MaCH or PLINK dosage format.
** Currently Minimac4 can ONLY handle M3VCF format files. If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4. The same holds for the option <code>--processReference</code> as well. Although the handle is made available, we will implement it in a later version.
** Parameters such as <code>--rounds</code>, <code>--states</code>, <code>--rec</code>, <code>--err</code> have been deactivated for now until we implement parameter estimation in minimac4.

= Usage =
The easiest way to install Minimac4 and its dependencies is to use the install.sh file provided.
git clone <nowiki>https://github.com/statgen/Minimac4.git</nowiki>
cd Minimac4
bash install.sh

A typical Minimac4 command line for imputation is as follows

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun

Here refPanel.m3vcf is the reference panel used in M3VCF format (e.g. 1000 Genomes), targetStudy.vcf is the phased GWAS data in VCF format, and testRun is the prefix for the output files.

=== Convert VCF to M3VCF ===
If the reference panel is in VCF format, please use [[Minimac3]] to convert it into M3VCF format first.
../bin/Minimac3 --refHaps refPanel.vcf \
--processReference \
--prefix refPanel

=== Multi-Threading ===
The following example shows the same analysis as above, but using 5 threads:

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun \
--cpus 5

=== Full List of Options ===
Users can always type the following for further support:
minimac4 --help

'''Please see [[Minimac4 Documentation | Minimac4 Documentation]] for detailed explanation of all available options.'''

= Reference Panels for Download =

Some commonly used reference panels are available for download here:

{| class="wikitable" style="text-align:center" border="1" cellpadding="2"
|- bgcolor="lightgray"
! width="150px" |Reference Panel
! width="100px" |Number of Samples
! width="100px" |File Format
! width="100px" |Parameter Estimates Available
! width="120px" |Chromosomes
! width="80px" |Link
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 3''' 
(version 5)
| rowspan=4 style="text-align:center" | '''2,504'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_VCF_Files.tar.gz Download] 
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download] 
|-
|NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_NO_ESTIMATES.tar.gz Download] 
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 1''' 
(version 3)
| rowspan=4 | '''1,092'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_VCF_Files.tar.gz Download]
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download]
|-
| NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_NO_ESTIMATES.tar.gz Download]
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|}

= Useful Wiki Pages =

There are a few pages in this Wiki that may be useful to for '''Minimac4''' users. Here are links to a few:

* [[Minimac4| Minimac4 Overview Page]]

* [[Minimac4 Documentation]]

* [[M3VCF Files| M3VCF Files]]

Minimac4

2019-07-20T03:10:48Z

Yukt: /* Usage */

= Introduction =

'''Minimac4 ''' is a latest version in the series of genotype imputation software - preceded by [[Minimac3|Minimac3]] (2015), [[Minimac2|Minimac2]] (2014), [[Minimac|minimac]] (2012) and [[MaCH|MaCH]] (2010). '''Minimac4''' is a lower memory and more computationally efficient implementation of the original algorithms with comparable imputation quality.

The Minimac3 mailing list has been renamed as the Minimac4 mailing list. If you were already a member, no need to re-join. If not, please join our [https://groups.google.com/forum/embed/?place=forum/minimac4-help&umich.edu| mailing list] to get updates about future releases or report possible bugs or email them to [mailto:yukt@umich.edu Ketian Yu] or [mailto:sayantan@umich.edu Sayantan Das].'''

= Download =

'''Minimac4 (version 1.0.0, released 2.14.2018)''' is currently available on [https://github.com/Santy-8128/Minimac4 Minimac4 Github]. Please follow the instructions in the GitHub repository for installation.

Commonly used reference panels in M3VCF format are available for download in [[#Reference Panels for Download | Reference Panels]].

= What's New =

The input file format, output file formats and typical command lines are the same in Minimac4 (as they were in minimac3). Some of the main new features are summarized below:

* '''Improved Speed - ''' Minimac4 is approximately '''6 times''' faster for 1000 Genomes Phase 1 and Phase 3 and '''2 times''' faster for the HRC reference panels at comparable accuracy (details of accuracy for imputing into 10 European samples are given here). The speed can be further improved by tuning the approximation parameters (see below), but we recommend using the default values.

* '''Automated Chunking - ''' Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back. This caps the memory usage across different chromosomes (memory requirement is based on chunk size, not chromosome size). The length of the chunk and the overlap can be controlled by the <code>--chunkLengthMb</code> and <code>--chunkLengthOverlapMb</code> options, although we recommend using the default values of 20 and 3, respectively.

* '''Approximations - ''' Minimac4 uses some simple approximations to speed up the imputation analyses. The levels of approximation can be controlled by the parameters <code>--probThreshold</code>, <code>--diffThreshold</code>, and <code>--topThreshold</code> (details given in Minimac4 Usage). Higher levels of approximation will reduce the compute time but marginally reduce the imputation accuracy. We recommend using the default values (0.01).

* '''Improved Chromosome X/Y Support - ''' Minimac4 can handle different ploidys in the same VCF file for imputation of sex chromosomes. For example, for the non-PAR region on chromosome X, males and females can be imputed together, irrespective of whether males are coded as haploids or diploids. However, each sample must have a fixed ploidy. Thus, PAR and non-PAR regions still need to be imputed separately. Please see Chromosome X Imputation for more details.

* '''Other Helpful Features'''
** We introduced a new feature called <code>--memUsage</code> that will estimate and report the memory required by Minimac4. This feature should be useful for users running their jobs on a compute cluster that requires memory specification.
** We introduced some other FORMAT options for the output dosage data, allowing users to retrieve haplotype dosages, genotype probabilities, genotype dosages or any other measure of summary that they want.
** We have fixed the bug related to FILTER=GENOTYPED and FILTER=GENOTYPED_ONLY which was causing a crash in bcftools.

* '''Obsolete Features'''
** In Minimac4, we removed the <code>--doseOutput</code> and <code>--hapOutput</code> options. Please use [[DosageConvertor]] to convert your files to MaCH or PLINK dosage format.
** Currently Minimac4 can ONLY handle M3VCF format files. If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4. The same holds for the option <code>--processReference</code> as well. Although the handle is made available, we will implement it in a later version.
** Parameters such as <code>--rounds</code>, <code>--states</code>, <code>--rec</code>, <code>--err</code> have been deactivated for now until we implement parameter estimation in minimac4.

= Usage =
The easiest way to install Minimac4 and its dependencies is to use the install.sh file provided.
git clone <nowiki>https://github.com/statgen/Minimac4.git</nowiki>
cd Minimac4
bash install.sh

A typical Minimac4 command line for imputation is as follows

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun

Here refPanel.m3vcf is the reference panel used in M3VCF format (e.g. 1000 Genomes), targetStudy.vcf is the phased GWAS data in VCF format, and testRun is the prefix for the output files.

=== Convert VCF to M3VCF ===
If the reference panel is in VCF format, please use [[Minimac3]] to convert it into M3VCF format first.
../bin/Minimac3 --refHaps refPanel.vcf \
--processReference \
--prefix refPanel

=== Multi-Threading ===
The following example shows the same analysis as above, but using 5 threads:

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun \
--cpus 5

=== Full List of Options ===
Users can always type the following for further support:
minimac4 --help

'''Please see [[Minimac4 Documentation | Minimac4 Documentation]] for detailed explanation of all available options.'''

= Reference Panels for Download =

Some commonly used reference panels are available for download here:

{| class="wikitable" style="text-align:center" border="1" cellpadding="2"
|- bgcolor="lightgray"
! width="150px" |Reference Panel
! width="100px" |Number of Samples
! width="100px" |File Format
! width="100px" |Parameter Estimates Available
! width="120px" |Chromosomes
! width="80px" |Link
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 3''' 
(version 5)
| rowspan=4 style="text-align:center" | '''2,504'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_VCF_Files.tar.gz Download] 
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download] 
|-
|NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_NO_ESTIMATES.tar.gz Download] 
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 1''' 
(version 3)
| rowspan=4 | '''1,092'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_VCF_Files.tar.gz Download]
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download]
|-
| NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_NO_ESTIMATES.tar.gz Download]
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|}

Minimac4

2019-07-20T03:09:33Z

Yukt: /* Usage */

= Introduction =

'''Minimac4 ''' is a latest version in the series of genotype imputation software - preceded by [[Minimac3|Minimac3]] (2015), [[Minimac2|Minimac2]] (2014), [[Minimac|minimac]] (2012) and [[MaCH|MaCH]] (2010). '''Minimac4''' is a lower memory and more computationally efficient implementation of the original algorithms with comparable imputation quality.

The Minimac3 mailing list has been renamed as the Minimac4 mailing list. If you were already a member, no need to re-join. If not, please join our [https://groups.google.com/forum/embed/?place=forum/minimac4-help&umich.edu| mailing list] to get updates about future releases or report possible bugs or email them to [mailto:yukt@umich.edu Ketian Yu] or [mailto:sayantan@umich.edu Sayantan Das].'''

= Download =

'''Minimac4 (version 1.0.0, released 2.14.2018)''' is currently available on [https://github.com/Santy-8128/Minimac4 Minimac4 Github]. Please follow the instructions in the GitHub repository for installation.

Commonly used reference panels in M3VCF format are available for download in [[#Reference Panels for Download | Reference Panels]].

= What's New =

The input file format, output file formats and typical command lines are the same in Minimac4 (as they were in minimac3). Some of the main new features are summarized below:

* '''Improved Speed - ''' Minimac4 is approximately '''6 times''' faster for 1000 Genomes Phase 1 and Phase 3 and '''2 times''' faster for the HRC reference panels at comparable accuracy (details of accuracy for imputing into 10 European samples are given here). The speed can be further improved by tuning the approximation parameters (see below), but we recommend using the default values.

* '''Automated Chunking - ''' Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back. This caps the memory usage across different chromosomes (memory requirement is based on chunk size, not chromosome size). The length of the chunk and the overlap can be controlled by the <code>--chunkLengthMb</code> and <code>--chunkLengthOverlapMb</code> options, although we recommend using the default values of 20 and 3, respectively.

* '''Approximations - ''' Minimac4 uses some simple approximations to speed up the imputation analyses. The levels of approximation can be controlled by the parameters <code>--probThreshold</code>, <code>--diffThreshold</code>, and <code>--topThreshold</code> (details given in Minimac4 Usage). Higher levels of approximation will reduce the compute time but marginally reduce the imputation accuracy. We recommend using the default values (0.01).

* '''Improved Chromosome X/Y Support - ''' Minimac4 can handle different ploidys in the same VCF file for imputation of sex chromosomes. For example, for the non-PAR region on chromosome X, males and females can be imputed together, irrespective of whether males are coded as haploids or diploids. However, each sample must have a fixed ploidy. Thus, PAR and non-PAR regions still need to be imputed separately. Please see Chromosome X Imputation for more details.

* '''Other Helpful Features'''
** We introduced a new feature called <code>--memUsage</code> that will estimate and report the memory required by Minimac4. This feature should be useful for users running their jobs on a compute cluster that requires memory specification.
** We introduced some other FORMAT options for the output dosage data, allowing users to retrieve haplotype dosages, genotype probabilities, genotype dosages or any other measure of summary that they want.
** We have fixed the bug related to FILTER=GENOTYPED and FILTER=GENOTYPED_ONLY which was causing a crash in bcftools.

* '''Obsolete Features'''
** In Minimac4, we removed the <code>--doseOutput</code> and <code>--hapOutput</code> options. Please use [[DosageConvertor]] to convert your files to MaCH or PLINK dosage format.
** Currently Minimac4 can ONLY handle M3VCF format files. If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4. The same holds for the option <code>--processReference</code> as well. Although the handle is made available, we will implement it in a later version.
** Parameters such as <code>--rounds</code>, <code>--states</code>, <code>--rec</code>, <code>--err</code> have been deactivated for now until we implement parameter estimation in minimac4.

= Usage =
The easiest way to install Minimac4 and its dependencies is to use the install.sh file provided.
git clone <nowiki>https://github.com/statgen/Minimac4.git</nowiki>
cd Minimac4
bash install.sh

A typical Minimac4 command line for imputation is as follows

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun

Here refPanel.m3vcf is the reference panel used in M3VCF format (e.g. 1000 Genomes), targetStudy.vcf is the phased GWAS data in VCF format, and testRun is the prefix for the output files.

If the reference panel is in VCF format, please use Minimac3 to convert it into M3VCF format first.
../bin/Minimac3 --refHaps refPanel.vcf \
--processReference \
--prefix refPanel

=== Multi-Threading ===
The following example shows the same analysis as above, but using 5 threads:

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun \
--cpus 5

=== Full List of Options ===
Users can always type the following for further support:
minimac4 --help

'''Please see [[Minimac4 Documentation | Minimac4 Documentation]] for detailed explanation of all available options.'''

= Reference Panels for Download =

Some commonly used reference panels are available for download here:

{| class="wikitable" style="text-align:center" border="1" cellpadding="2"
|- bgcolor="lightgray"
! width="150px" |Reference Panel
! width="100px" |Number of Samples
! width="100px" |File Format
! width="100px" |Parameter Estimates Available
! width="120px" |Chromosomes
! width="80px" |Link
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 3''' 
(version 5)
| rowspan=4 style="text-align:center" | '''2,504'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_VCF_Files.tar.gz Download] 
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download] 
|-
|NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_NO_ESTIMATES.tar.gz Download] 
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 1''' 
(version 3)
| rowspan=4 | '''1,092'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_VCF_Files.tar.gz Download]
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download]
|-
| NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_NO_ESTIMATES.tar.gz Download]
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|}

Minimac4

2019-07-20T03:02:57Z

Yukt: /* Usage */

= Introduction =

'''Minimac4 ''' is a latest version in the series of genotype imputation software - preceded by [[Minimac3|Minimac3]] (2015), [[Minimac2|Minimac2]] (2014), [[Minimac|minimac]] (2012) and [[MaCH|MaCH]] (2010). '''Minimac4''' is a lower memory and more computationally efficient implementation of the original algorithms with comparable imputation quality.

The Minimac3 mailing list has been renamed as the Minimac4 mailing list. If you were already a member, no need to re-join. If not, please join our [https://groups.google.com/forum/embed/?place=forum/minimac4-help&umich.edu| mailing list] to get updates about future releases or report possible bugs or email them to [mailto:yukt@umich.edu Ketian Yu] or [mailto:sayantan@umich.edu Sayantan Das].'''

= Download =

'''Minimac4 (version 1.0.0, released 2.14.2018)''' is currently available on [https://github.com/Santy-8128/Minimac4 Minimac4 Github]. Please follow the instructions in the GitHub repository for installation.

Commonly used reference panels in M3VCF format are available for download in [[#Reference Panels for Download | Reference Panels]].

= What's New =

The input file format, output file formats and typical command lines are the same in Minimac4 (as they were in minimac3). Some of the main new features are summarized below:

* '''Improved Speed - ''' Minimac4 is approximately '''6 times''' faster for 1000 Genomes Phase 1 and Phase 3 and '''2 times''' faster for the HRC reference panels at comparable accuracy (details of accuracy for imputing into 10 European samples are given here). The speed can be further improved by tuning the approximation parameters (see below), but we recommend using the default values.

* '''Automated Chunking - ''' Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back. This caps the memory usage across different chromosomes (memory requirement is based on chunk size, not chromosome size). The length of the chunk and the overlap can be controlled by the <code>--chunkLengthMb</code> and <code>--chunkLengthOverlapMb</code> options, although we recommend using the default values of 20 and 3, respectively.

* '''Approximations - ''' Minimac4 uses some simple approximations to speed up the imputation analyses. The levels of approximation can be controlled by the parameters <code>--probThreshold</code>, <code>--diffThreshold</code>, and <code>--topThreshold</code> (details given in Minimac4 Usage). Higher levels of approximation will reduce the compute time but marginally reduce the imputation accuracy. We recommend using the default values (0.01).

* '''Improved Chromosome X/Y Support - ''' Minimac4 can handle different ploidys in the same VCF file for imputation of sex chromosomes. For example, for the non-PAR region on chromosome X, males and females can be imputed together, irrespective of whether males are coded as haploids or diploids. However, each sample must have a fixed ploidy. Thus, PAR and non-PAR regions still need to be imputed separately. Please see Chromosome X Imputation for more details.

* '''Other Helpful Features'''
** We introduced a new feature called <code>--memUsage</code> that will estimate and report the memory required by Minimac4. This feature should be useful for users running their jobs on a compute cluster that requires memory specification.
** We introduced some other FORMAT options for the output dosage data, allowing users to retrieve haplotype dosages, genotype probabilities, genotype dosages or any other measure of summary that they want.
** We have fixed the bug related to FILTER=GENOTYPED and FILTER=GENOTYPED_ONLY which was causing a crash in bcftools.

* '''Obsolete Features'''
** In Minimac4, we removed the <code>--doseOutput</code> and <code>--hapOutput</code> options. Please use [[DosageConvertor]] to convert your files to MaCH or PLINK dosage format.
** Currently Minimac4 can ONLY handle M3VCF format files. If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4. The same holds for the option <code>--processReference</code> as well. Although the handle is made available, we will implement it in a later version.
** Parameters such as <code>--rounds</code>, <code>--states</code>, <code>--rec</code>, <code>--err</code> have been deactivated for now until we implement parameter estimation in minimac4.

= Usage =
The easiest way to install Minimac4 and its dependencies is to use the install.sh file provided.
git clone <nowiki>https://github.com/statgen/Minimac4.git</nowiki>
cd Minimac4
bash install.sh

A typical Minimac4 command line for imputation is as follows

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun

Here refPanel.m3vcf is the reference panel used in M3VCF format (e.g. 1000 Genomes), targetStudy.vcf is the phased GWAS data in VCF format, and testRun is the prefix for the output files.

=== Multi-Threading ===
The following example shows the same analysis as above, but using 5 threads:

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun \
--cpus 5

=== Full List of Options ===
Users can always type the following for further support:
minimac4 --help

'''Please see [[Minimac4 Documentation | Minimac4 Documentation]] for detailed explanation of all available options.'''

= Reference Panels for Download =

Some commonly used reference panels are available for download here:

{| class="wikitable" style="text-align:center" border="1" cellpadding="2"
|- bgcolor="lightgray"
! width="150px" |Reference Panel
! width="100px" |Number of Samples
! width="100px" |File Format
! width="100px" |Parameter Estimates Available
! width="120px" |Chromosomes
! width="80px" |Link
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 3''' 
(version 5)
| rowspan=4 style="text-align:center" | '''2,504'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_VCF_Files.tar.gz Download] 
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download] 
|-
|NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_NO_ESTIMATES.tar.gz Download] 
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 1''' 
(version 3)
| rowspan=4 | '''1,092'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_VCF_Files.tar.gz Download]
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download]
|-
| NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_NO_ESTIMATES.tar.gz Download]
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|}

Minimac4 Documentation

2019-07-20T02:30:39Z

Yukt: /* Subset Parameters */

Minimac4 Documentation

2019-07-20T02:27:47Z

Yukt: /* PhoneHome */

Minimac4 Documentation

2019-07-20T02:25:42Z

Yukt: /* Subset Parameters */

A typical Minimac4 command line would have the following parameter options:

Reference Haplotypes : --refHaps [], --passOnly, --rsid,
--referenceEstimates [ON],
--mapFile [docs/geneticMapFile.b38.map.txt.gz]
Target Haplotypes : --haps []
Output Parameters : --prefix [Minimac4.Output], --estimate,
--nobgzip, --vcfBuffer [200], --format [GT,DS],
--allTypedSites, --meta, --memUsage
Chunking Parameters : --ChunkLengthMb [20.00], --ChunkOverlapMb [3.00]
Subset Parameters : --chr [], --start, --end, --window
Approximation Parameters : --minimac3, --probThreshold [0.01],
--diffThreshold [0.01], --topThreshold [0.01]
Other Parameters : --log, --help, --cpus [1], --params
PhoneHome : --noPhoneHome, --phoneHomeThinning [50]

Among all, '''--refHaps''' and '''--haps''' are required.

== Reference Haplotypes ==
;--refHaps <input_m3vcf_filename>
: This option defines the reference panel in M3VCF format to impute against.
: If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4.

; --passOnly
: DEACTIVATED for now. OFF by default. If ON, only variants will FILTER=PASS will be recorded from reference VCF file (does NOT work on M3VCF files yet).

;--rsid
: OFF by default. If ON, Minimac4 will only import RS ID of variants from ID column of reference file (if available).

;--referenceEstimates
: ON by default. If ON, Minimac4 expects the input M3VCF file comes with parameter estimate; otherwise, a genetic map file for option <code>--mapFile</code> is required.

;--mapFile <input_genetic_map_file>
: This option is automatically ignored except when <code>--referenceEstimates</code> is OFF.
: It defines the genetic map file used for recombination rate estimation during imputation.
: The input genetic map file should be tab-separated, with the first row as its header, and the columns representing chromosome id, base pair position, cumulative recombination rate in cM/Mb, and genetic map coordinates in cM, respectively.

== Target Haplotypes ==
;--haps <input_vcf_filename>
: This option defines the pre-phased target genotype data in VCF format to impute.

== Output Parameters ==
; --prefix <output_prefix>
: This option defines the output filename prefix for all files generated by Minimac4.
: If this option is omitted, all output files will have the prefix "Minimac4.Output" in the current working directory.

; --estimate
: DEACTIVATED for now. This option is equivalent to the option <code>--processReference</code> in [[Minimac3 Usage|Minimac3]].

; --nobgzip
: OFF by default. If ON, output files will be NOT bgzipped.

; --vcfBuffer
: This option defines the maximum number of samples in the target genotype data to be imputed at a time. By default, it is set as 200, or the total number of samples, whichever is smaller.
: Note that the larger the value is, the more memory Minimac4 will consume.

; --format
: This option specifies which fields to output for the FORMAT field in output imputed VCF file. Available handles are <code>GT</code>,<code>DS</code>,<code>HDS</code>,<code>GP</code>,<code>SD</code>. Default setting is <code>GT,DS</code>.
:* '''GT''' - Estimated most likely genotype.
:* '''DS''' - Estimated alternate allele dosage [P(0/1)+2*P(1/1)].
:* '''HDS''' - Estimated phased haploid alternate allele dosage.
:* '''GP''' - Estimated Posterior Genotype Probabilities P(0/0), P(0/1) and P(1/1).
:* '''SD''' - Estimated Variance of Posterior Genotype Probabilities.

;--allTypedSites
: OFF by default. If ON, Minimac4 will also include variants that were genotyped but NOT in the reference panel in the output files (and imputes any missing data in such variants to the major allele frequency).

;--meta
: OFF by default. If ON, Minimac4 will generate a separate file that can be used by [[MetaMinimac2|MetaMinimac2]] for meta-imputation.

;--memUsage
: OFF by default. If ON, Minimac4 will not perform imputation. Instead, it will estimate memory that imputation would consume based on a single chunk.

== Chunking Parameters ==
Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back.

;--ChunkLengthMb <float_number>
: This option defines the average length of chunks in units of million base pairs (Mb). The input value should be within (0.001, 300]. The default setting is 20.

;--ChunkOverlapMb <float_number>
: This option defines the length of overlap between chunks in units of Mb, 3Mb by default. The valid input value should be within (0.001, 300].
: The overlap length should be at most 1/3 of the chunk length, if larger, Minimac4 will automatically reduce it to 1/3 of the chunk length.

== Subset Parameters ==
The subset parameters are required if the user wishes to impute into a particular region of the chromosome rather than the whole chromosome (typically used when running imputation in chunks). If using the subset parameters, a default window of additional 500 Kbp is applied on either side as the buffer region, unless otherwise specified by the user. Variants from the buffer region are only used for imputation and not reported in the final output.
For example, to analyze chromosome 6 from position 1000000 to position 2000000 with 300000 base positions on either side as a buffer, one must use <code>--chr 6 --from 1000000 --to 2000000 --window 300000</code>.

; --chr <chromosome>
: This option specifies the chromosome number for which we will carry out imputation.
: Note that it is required to specify non-zero values for <code>--start</code> and <code>--end</code> when <code>--chr</code> option is used.

; --start <integer>
: This option specifies the start position of the region to be analyzed. Would not work without <code>--chr</code> option.

; --end <integer>
: This option specifies the end position of the region to be analyzed. Would not work without <code>--chr</code> option.

; --window <integer>
: This option specifies the length of buffer region in units of base pairs on either side of the region to be analyzed. Would not work without <code>--chr</code> option; otherwise, it is set as 500000 by default.

== Approximation Parameters ==
;--minimac3
: OFF by default. If ON, Minimac3 algorithm will be used for imputation.

;--probThreshold <float_number>

;--diffThreshold <float_number>

;--topThreshold <float_number>

== Other Parameters ==
; --log
: OFF by default. If ON, information including warnings and errors will be saved into <output_prefix>.logfile, instead printed on the screen.

; --help
: If ON, it will show the list of all available options.

;--cpus <integer>
: This option defines the number of cpus for parallel computing, 1 by default.

== PhoneHome ==
;--noPhoneHome
: OFF by default. If ON, code will NOT send a SUCCESS/FAILURE status of the execution to home server.

;--phoneHomeThinning <integer>
: Percentage probability of sending SUCCESS/FAILURE status of the execution to home server, 50 by default.

Minimac4 Documentation

2019-07-20T02:15:52Z

Yukt: Almost done.

A typical Minimac4 command line would have the following parameter options:

Reference Haplotypes : --refHaps [], --passOnly, --rsid,
--referenceEstimates [ON],
--mapFile [docs/geneticMapFile.b38.map.txt.gz]
Target Haplotypes : --haps []
Output Parameters : --prefix [Minimac4.Output], --estimate,
--nobgzip, --vcfBuffer [200], --format [GT,DS],
--allTypedSites, --meta, --memUsage
Chunking Parameters : --ChunkLengthMb [20.00], --ChunkOverlapMb [3.00]
Subset Parameters : --chr [], --start, --end, --window
Approximation Parameters : --minimac3, --probThreshold [0.01],
--diffThreshold [0.01], --topThreshold [0.01]
Other Parameters : --log, --help, --cpus [1], --params
PhoneHome : --noPhoneHome, --phoneHomeThinning [50]

Among all, '''--refHaps''' and '''--haps''' are required.

== Reference Haplotypes ==
;--refHaps <input_m3vcf_filename>
: This option defines the reference panel in M3VCF format to impute against.
: If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4.

; --passOnly
: DEACTIVATED for now. OFF by default. If ON, only variants will FILTER=PASS will be recorded from reference VCF file (does NOT work on M3VCF files yet).

;--rsid
: OFF by default. If ON, Minimac4 will only import RS ID of variants from ID column of reference file (if available).

;--referenceEstimates
: ON by default. If ON, Minimac4 expects the input M3VCF file comes with parameter estimate; otherwise, a genetic map file for option <code>--mapFile</code> is required.

;--mapFile <input_genetic_map_file>
: This option is automatically ignored except when <code>--referenceEstimates</code> is OFF.
: It defines the genetic map file used for recombination rate estimation during imputation.
: The input genetic map file should be tab-separated, with the first row as its header, and the columns representing chromosome id, base pair position, cumulative recombination rate in cM/Mb, and genetic map coordinates in cM, respectively.

== Target Haplotypes ==
;--haps <input_vcf_filename>
: This option defines the pre-phased target genotype data in VCF format to impute.

== Output Parameters ==
; --prefix <output_prefix>
: This option defines the output filename prefix for all files generated by Minimac4.
: If this option is omitted, all output files will have the prefix "Minimac4.Output" in the current working directory.

; --estimate
: DEACTIVATED for now. This option is equivalent to the option <code>--processReference</code> in [[Minimac3 Usage|Minimac3]].

; --nobgzip
: OFF by default. If ON, output files will be NOT bgzipped.

; --vcfBuffer
: This option defines the maximum number of samples in the target genotype data to be imputed at a time. By default, it is set as 200, or the total number of samples, whichever is smaller.
: Note that the larger the value is, the more memory Minimac4 will consume.

; --format
: This option specifies which fields to output for the FORMAT field in output imputed VCF file. Available handles are <code>GT</code>,<code>DS</code>,<code>HDS</code>,<code>GP</code>,<code>SD</code>. Default setting is <code>GT,DS</code>.
:* '''GT''' - Estimated most likely genotype.
:* '''DS''' - Estimated alternate allele dosage [P(0/1)+2*P(1/1)].
:* '''HDS''' - Estimated phased haploid alternate allele dosage.
:* '''GP''' - Estimated Posterior Genotype Probabilities P(0/0), P(0/1) and P(1/1).
:* '''SD''' - Estimated Variance of Posterior Genotype Probabilities.

;--allTypedSites
: OFF by default. If ON, Minimac4 will also include variants that were genotyped but NOT in the reference panel in the output files (and imputes any missing data in such variants to the major allele frequency).

;--meta
: OFF by default. If ON, Minimac4 will generate a separate file that can be used by [[MetaMinimac2|MetaMinimac2]] for meta-imputation.

;--memUsage
: OFF by default. If ON, Minimac4 will not perform imputation. Instead, it will estimate memory that imputation would consume based on a single chunk.

== Chunking Parameters ==
Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back.

;--ChunkLengthMb <float_number>
: This option defines the average length of chunks in units of million base pairs (Mb). The input value should be within (0.001, 300]. The default setting is 20.

;--ChunkOverlapMb <float_number>
: This option defines the length of overlap between chunks in units of Mb, 3Mb by default. The valid input value should be within (0.001, 300].
: The overlap length should be at most 1/3 of the chunk length, if larger, Minimac4 will automatically reduce it to 1/3 of the chunk length.

== Subset Parameters ==
This set of parameters are used when imputing a specific region instead of all the sites covered by the reference panel.

; --chr <chromosome>
: This option specifies the chromosome number for which we will carry out imputation.
: Note that it is required to specify non-zero values for <code>--start</code> and <code>--end</code> when <code>--chr</code> option is used.

; --start <integer>
: This option specifies the start position of the region to be analyzed. Would not work without <code>--chr</code> option.

; --end <integer>
: This option specifies the end position of the region to be analyzed. Would not work without <code>--chr</code> option.

; --window <integer>
: This option specifies the length of buffer region in units of base pairs on either side of the region to be analyzed. Would not work without <code>--chr</code> option; otherwise, it is set as 500000 by default.

== Approximation Parameters ==
;--minimac3
: OFF by default. If ON, Minimac3 algorithm will be used for imputation.

;--probThreshold <float_number>

;--diffThreshold <float_number>

;--topThreshold <float_number>

== Other Parameters ==
; --log
: OFF by default. If ON, information including warnings and errors will be saved into <output_prefix>.logfile, instead printed on the screen.

; --help
: If ON, it will show the list of all available options.

;--cpus <integer>
: This option defines the number of cpus for parallel computing, 1 by default.

== PhoneHome ==
;--noPhoneHome
: OFF by default. If ON, code will NOT send a SUCCESS/FAILURE status of the execution to home server.

;--phoneHomeThinning <integer>
: Percentage probability of sending SUCCESS/FAILURE status of the execution to home server, 50 by default.

Minimac4 Documentation

2019-07-17T00:50:33Z

Yukt: Add output options

Minimac4

2019-07-16T22:30:35Z

Yukt:

= Introduction =

'''Minimac4 ''' is a latest version in the series of genotype imputation software - preceded by [[Minimac3|Minimac3]] (2015), [[Minimac2|Minimac2]] (2014), [[Minimac|minimac]] (2012) and [[MaCH|MaCH]] (2010). '''Minimac4''' is a lower memory and more computationally efficient implementation of the original algorithms with comparable imputation quality.

The Minimac3 mailing list has been renamed as the Minimac4 mailing list. If you were already a member, no need to re-join. If not, please join our [https://groups.google.com/forum/embed/?place=forum/minimac4-help&umich.edu| mailing list] to get updates about future releases or report possible bugs or email them to [mailto:yukt@umich.edu Ketian Yu] or [mailto:sayantan@umich.edu Sayantan Das].'''

= Download =

'''Minimac4 (version 1.0.0, released 2.14.2018)''' is currently available on [https://github.com/Santy-8128/Minimac4 Minimac4 Github]. Please follow the instructions in the GitHub repository for installation.

Commonly used reference panels in M3VCF format are available for download in [[#Reference Panels for Download | Reference Panels]].

= What's New =

The input file format, output file formats and typical command lines are the same in Minimac4 (as they were in minimac3). Some of the main new features are summarized below:

* '''Improved Speed - ''' Minimac4 is approximately '''6 times''' faster for 1000 Genomes Phase 1 and Phase 3 and '''2 times''' faster for the HRC reference panels at comparable accuracy (details of accuracy for imputing into 10 European samples are given here). The speed can be further improved by tuning the approximation parameters (see below), but we recommend using the default values.

* '''Automated Chunking - ''' Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back. This caps the memory usage across different chromosomes (memory requirement is based on chunk size, not chromosome size). The length of the chunk and the overlap can be controlled by the <code>--chunkLengthMb</code> and <code>--chunkLengthOverlapMb</code> options, although we recommend using the default values of 20 and 3, respectively.

* '''Approximations - ''' Minimac4 uses some simple approximations to speed up the imputation analyses. The levels of approximation can be controlled by the parameters <code>--probThreshold</code>, <code>--diffThreshold</code>, and <code>--topThreshold</code> (details given in Minimac4 Usage). Higher levels of approximation will reduce the compute time but marginally reduce the imputation accuracy. We recommend using the default values (0.01).

* '''Improved Chromosome X/Y Support - ''' Minimac4 can handle different ploidys in the same VCF file for imputation of sex chromosomes. For example, for the non-PAR region on chromosome X, males and females can be imputed together, irrespective of whether males are coded as haploids or diploids. However, each sample must have a fixed ploidy. Thus, PAR and non-PAR regions still need to be imputed separately. Please see Chromosome X Imputation for more details.

* '''Other Helpful Features'''
** We introduced a new feature called <code>--memUsage</code> that will estimate and report the memory required by Minimac4. This feature should be useful for users running their jobs on a compute cluster that requires memory specification.
** We introduced some other FORMAT options for the output dosage data, allowing users to retrieve haplotype dosages, genotype probabilities, genotype dosages or any other measure of summary that they want.
** We have fixed the bug related to FILTER=GENOTYPED and FILTER=GENOTYPED_ONLY which was causing a crash in bcftools.

* '''Obsolete Features'''
** In Minimac4, we removed the <code>--doseOutput</code> and <code>--hapOutput</code> options. Please use [[DosageConvertor]] to convert your files to MaCH or PLINK dosage format.
** Currently Minimac4 can ONLY handle M3VCF format files. If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4. The same holds for the option <code>--processReference</code> as well. Although the handle is made available, we will implement it in a later version.
** Parameters such as <code>--rounds</code>, <code>--states</code>, <code>--rec</code>, <code>--err</code> have been deactivated for now until we implement parameter estimation in minimac4.

= Usage =
The easiest way to install Minimac4 and its dependencies is to use the install.sh file provided.
git clone <nowiki>https://github.com/statgen/Minimac4.git</nowiki>
cd Minimac4
bash install.sh

A typical Minimac4 command line for imputation is as follows

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun

Here refPanel.m3vcf is the reference panel used in M3VCF format (e.g. 1000 Genomes), targetStudy.vcf is the phased GWAS data in VCF format, and testRun is the prefix for the output files.

Users can always type the following for further support:
minimac4 --help

'''Please see [[Minimac4 Documentation | Minimac4 Documentation]] for detailed explanation of all available options.'''

= Reference Panels for Download =

Some commonly used reference panels are available for download here:

{| class="wikitable" style="text-align:center" border="1" cellpadding="2"
|- bgcolor="lightgray"
! width="150px" |Reference Panel
! width="100px" |Number of Samples
! width="100px" |File Format
! width="100px" |Parameter Estimates Available
! width="120px" |Chromosomes
! width="80px" |Link
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 3''' 
(version 5)
| rowspan=4 style="text-align:center" | '''2,504'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_VCF_Files.tar.gz Download] 
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download] 
|-
|NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_NO_ESTIMATES.tar.gz Download] 
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 1''' 
(version 3)
| rowspan=4 | '''1,092'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_VCF_Files.tar.gz Download]
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download]
|-
| NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_NO_ESTIMATES.tar.gz Download]
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|}

Minimac4 Documentation

2019-07-16T22:29:21Z

Yukt: half done

Minimac4

2019-07-16T21:13:33Z

Yukt: /* Usage */

= Introduction =

'''Minimac4 ''' is a latest version in the series of genotype imputation software - preceded by [[Minimac3|Minimac3]] (2015), [[Minimac2|Minimac2]] (2014), [[Minimac|minimac]] (2012) and [[MaCH|MaCH]] (2010). '''Minimac4''' is a lower memory and more computationally efficient implementation of the original algorithms with comparable imputation quality.

The Minimac3 mailing list has been renamed as the Minimac4 mailing list. If you were already a member, no need to re-join. If not, please join our [https://groups.google.com/forum/embed/?place=forum/minimac4-help&umich.edu| mailing list] to get updates about future releases or report possible bugs or email them to [mailto:yukt@umich.edu Ketian Yu] or [mailto:sayantan@umich.edu Sayantan Das].'''

= Download =

'''Minimac4 (version 1.0.0, released 2.14.2018)''' is currently available on [https://github.com/Santy-8128/Minimac4 Minimac4 Github]. Please follow the instructions in the GitHub repository for installation.

Commonly used reference panels in M3VCF format are available for download in [[#Reference Panels for Download | Reference Panels]].

= What's New =

The input file format, output file formats and typical command lines are the same in Minimac4 (as they were in minimac3). Some of the main new features are summarized below:

* '''Improved Speed - ''' Minimac4 is approximately '''6 times''' faster for 1000 Genomes Phase 1 and Phase 3 and '''2 times''' faster for the HRC reference panels at comparable accuracy (details of accuracy for imputing into 10 European samples are given here). The speed can be further improved by tuning the approximation parameters (see below), but we recommend using the default values.

* '''Automated Chunking - ''' Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back. This caps the memory usage across different chromosomes (memory requirement is based on chunk size, not chromosome size). The length of the chunk and the overlap can be controlled by the <code>--chunkLengthMb</code> and <code>--chunkLengthOverlapMb</code> options, although we recommend using the default values of 20 and 3, respectively.

* '''Approximations - ''' Minimac4 uses some simple approximations to speed up the imputation analyses. The levels of approximation can be controlled by the parameters <code>--probThreshold</code>, <code>--diffThreshold</code>, and <code>--topThreshold</code> (details given in Minimac4 Usage). Higher levels of approximation will reduce the compute time but marginally reduce the imputation accuracy. We recommend using the default values (0.01).

* '''Improved Chromosome X/Y Support - ''' Minimac4 can handle different ploidys in the same VCF file for imputation of sex chromosomes. For example, for the non-PAR region on chromosome X, males and females can be imputed together, irrespective of whether males are coded as haploids or diploids. However, each sample must have a fixed ploidy. Thus, PAR and non-PAR regions still need to be imputed separately. Please see Chromosome X Imputation for more details.

* '''Other Helpful Features'''
** We introduced a new feature called <code>--memUsage</code> that will estimate and report the memory required by Minimac4. This feature should be useful for users running their jobs on a compute cluster that requires memory specification.
** We introduced some other FORMAT options for the output dosage data, allowing users to retrieve haplotype dosages, genotype probabilities, genotype dosages or any other measure of summary that they want.
** We have fixed the bug related to FILTER=GENOTYPED and FILTER=GENOTYPED_ONLY which was causing a crash in bcftools.

* '''Obsolete Features'''
** In Minimac4, we removed the <code>--doseOutput</code> and <code>--hapOutput</code> options. Please use [[DosageConvertor]] to convert your files to MaCH or PLINK dosage format.
** Currently Minimac4 can ONLY handle M3VCF format files. If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4. The same holds for the option <code>--processReference</code> as well. Although the handle is made available, we will implement it in a later version.
** Parameters such as <code>--rounds</code>, <code>--states</code>, <code>--rec</code>, <code>--err</code> have been deactivated for now until we implement parameter estimation in minimac4.

= Usage =
The easiest way to install Minimac4 and its dependencies is to use the install.sh file provided.
git clone <nowiki>https://github.com/statgen/Minimac4.git</nowiki>
cd Minimac4
bash install.sh

A typical Minimac4 command line for imputation is as follows

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun

Here refPanel.m3vcf is the reference panel used in M3VCF format (e.g. 1000 Genomes), targetStudy.vcf is the phased GWAS data in VCF format, and testRun is the prefix for the output files.

Users can always type the following for further support:
minimac4 --help

'''Please see [[Minimac4 Documentation | Minimac3 Documentation]] for detailed explanation of all available options.'''

= Reference Panels for Download =

Some commonly used reference panels are available for download here:

{| class="wikitable" style="text-align:center" border="1" cellpadding="2"
|- bgcolor="lightgray"
! width="150px" |Reference Panel
! width="100px" |Number of Samples
! width="100px" |File Format
! width="100px" |Parameter Estimates Available
! width="120px" |Chromosomes
! width="80px" |Link
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 3''' 
(version 5)
| rowspan=4 style="text-align:center" | '''2,504'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_VCF_Files.tar.gz Download] 
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download] 
|-
|NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_NO_ESTIMATES.tar.gz Download] 
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 1''' 
(version 3)
| rowspan=4 | '''1,092'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_VCF_Files.tar.gz Download]
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download]
|-
| NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_NO_ESTIMATES.tar.gz Download]
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|}

Minimac4

2019-07-16T20:52:08Z

Yukt: Usage added. Full documentation will be on a separate page.

= Introduction =

'''Minimac4 ''' is a latest version in the series of genotype imputation software - preceded by [[Minimac3|Minimac3]] (2015), [[Minimac2|Minimac2]] (2014), [[Minimac|minimac]] (2012) and [[MaCH|MaCH]] (2010). '''Minimac4''' is a lower memory and more computationally efficient implementation of the original algorithms with comparable imputation quality.

The Minimac3 mailing list has been renamed as the Minimac4 mailing list. If you were already a member, no need to re-join. If not, please join our [https://groups.google.com/forum/embed/?place=forum/minimac4-help&umich.edu| mailing list] to get updates about future releases or report possible bugs or email them to [mailto:yukt@umich.edu Ketian Yu] or [mailto:sayantan@umich.edu Sayantan Das].'''

= Download =

'''Minimac4 (version 1.0.0, released 2.14.2018)''' is currently available on [https://github.com/Santy-8128/Minimac4 Minimac4 Github]. Please follow the instructions in the GitHub repository for installation.

Commonly used reference panels in M3VCF format are available for download in [[#Reference Panels for Download | Reference Panels]].

= What's New =

The input file format, output file formats and typical command lines are the same in Minimac4 (as they were in minimac3). Some of the main new features are summarized below:

* '''Improved Speed - ''' Minimac4 is approximately '''6 times''' faster for 1000 Genomes Phase 1 and Phase 3 and '''2 times''' faster for the HRC reference panels at comparable accuracy (details of accuracy for imputing into 10 European samples are given here). The speed can be further improved by tuning the approximation parameters (see below), but we recommend using the default values.

* '''Automated Chunking - ''' Minimac4 automatically chunks the whole chromosome (into overlapping chunks), analyzes each chunk sequentially and then concatenates the imputed chunks back. This caps the memory usage across different chromosomes (memory requirement is based on chunk size, not chromosome size). The length of the chunk and the overlap can be controlled by the <code>--chunkLengthMb</code> and <code>--chunkLengthOverlapMb</code> options, although we recommend using the default values of 20 and 3, respectively.

* '''Approximations - ''' Minimac4 uses some simple approximations to speed up the imputation analyses. The levels of approximation can be controlled by the parameters <code>--probThreshold</code>, <code>--diffThreshold</code>, and <code>--topThreshold</code> (details given in Minimac4 Usage). Higher levels of approximation will reduce the compute time but marginally reduce the imputation accuracy. We recommend using the default values (0.01).

* '''Improved Chromosome X/Y Support - ''' Minimac4 can handle different ploidys in the same VCF file for imputation of sex chromosomes. For example, for the non-PAR region on chromosome X, males and females can be imputed together, irrespective of whether males are coded as haploids or diploids. However, each sample must have a fixed ploidy. Thus, PAR and non-PAR regions still need to be imputed separately. Please see Chromosome X Imputation for more details.

* '''Other Helpful Features'''
** We introduced a new feature called <code>--memUsage</code> that will estimate and report the memory required by Minimac4. This feature should be useful for users running their jobs on a compute cluster that requires memory specification.
** We introduced some other FORMAT options for the output dosage data, allowing users to retrieve haplotype dosages, genotype probabilities, genotype dosages or any other measure of summary that they want.
** We have fixed the bug related to FILTER=GENOTYPED and FILTER=GENOTYPED_ONLY which was causing a crash in bcftools.

* '''Obsolete Features'''
** In Minimac4, we removed the <code>--doseOutput</code> and <code>--hapOutput</code> options. Please use [[DosageConvertor]] to convert your files to MaCH or PLINK dosage format.
** Currently Minimac4 can ONLY handle M3VCF format files. If your reference panel is in VCF format, please use [[Minimac3]] to convert the VCF file to M3VCF (along with parameter estimation) and then use that M3VCF for imputation using Minimac4. The same holds for the option <code>--processReference</code> as well. Although the handle is made available, we will implement it in a later version.
** Parameters such as <code>--rounds</code>, <code>--states</code>, <code>--rec</code>, <code>--err</code> have been deactivated for now until we implement parameter estimation in minimac4.

= Usage =
The easiest way to install Minimac4 and its dependencies is to use the install.sh file provided.
git clone <nowiki>https://github.com/statgen/Minimac4.git</nowiki>
cd Minimac4
bash install.sh

A typical Minimac4 command line for imputation is as follows

minimac4 --refHaps refPanel.m3vcf \
--haps targetStudy.vcf \
--prefix testRun

Here refPanel.m3vcf is the reference panel used in M3VCF format (e.g. 1000 Genomes), targetStudy.vcf is the phased GWAS data in VCF format, and testRun is the prefix for the output files.

Users can always type the following for further support:
minimac4 --help

= Reference Panels for Download =

Some commonly used reference panels are available for download here:

{| class="wikitable" style="text-align:center" border="1" cellpadding="2"
|- bgcolor="lightgray"
! width="150px" |Reference Panel
! width="100px" |Number of Samples
! width="100px" |File Format
! width="100px" |Parameter Estimates Available
! width="120px" |Chromosomes
! width="80px" |Link
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 3''' 
(version 5)
| rowspan=4 style="text-align:center" | '''2,504'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_VCF_Files.tar.gz Download] 
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download] 
|-
|NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_M3VCF_FILES_NO_ESTIMATES.tar.gz Download] 
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P3_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|-
| rowspan=4 | '''1000 Genomes''' 
'''Phase 1''' 
(version 3)
| rowspan=4 | '''1,092'''
| '''VCF'''
| -
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_VCF_Files.tar.gz Download]
|-
| rowspan=2 style="text-align:center" | '''M3VCF'''
| YES
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_WITH_ESTIMATES.tar.gz Download]
|-
| NO
| 1-22,X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_M3VCF_FILES_NO_ESTIMATES.tar.gz Download]
|-
| '''VCF''','''M3VCF'''
| YES
| X
| [ftp://share.sph.umich.edu/minimac3/G1K_P1_CHR_X_VCF_M3VCF_FILES.tar.gz Download] 
|}