In our experience, userfriendliness is often the deciding factor in the choice of software to. If the user plans to perform phasing, we recommend a larger states value 200. Therefore, key components for a successful imputation include not only a promising imputation method but also an appropriate reference panel. In addition, accuracy of genotype imputation from medium to highdensity single nucleotide polymorphisms snp chip panels to wholegenome sequence can be predicted well using a simple linear model defined in this study. Download reference data that you can use to impute genotypes in. Shapeit has primarily been developed by dr olivier delaneau through a collaborative project between the research groups of prof jeanfrancois zagury at. Abstract multiple imputation provides a useful strategy for dealing with data sets that have missing values. An excellent discussion of genotype imputation enables powerful combined analyses.
Li y, willer cj, sanna s and abecasis gr 2009 genotype imputation. The method here is to perform multiple imputation for one marker or loci at. Evaluating the accuracy of imputation methods in a five. The vcf files will be downloaded with their counterpart. List of haplotype estimation and genotype imputation software. Download reference data that you can use to impute genotypes in your. The current version of fimpute can handle snp markers only. Genotype imputation is a valuable tool in genetic studies of complex disease, and optimizing imputation accuracy is important for conducting analyses with imputed data.
The beagle algorithm uses a modified version of the li and stephens haplotype frequency model that reduces the space requirements and a preprocessing step that recomputes an original reference panel into a composite reference haplotypes. I know that we can impute missing genotypes in gwas studies by inferring from the hapmap or genomes genotypes. Minimac is a low memory, computationally efficient implementation of the mach algorithm for genotype imputation that supports multithreading. Multiple imputation using sas software yuan journal of. In this study, our goal was to examine two highly popular genotype imputation software packages, impute v2 and. Mach, beagle, or provide specially designed file format conversion tools e. General imputation softwares to impute missing genotypes in. The raw data consists of a set of genotyped snps with a large number of snps without any genotype data a. Genotype imputation is an important tool for genomewide association studies as it increases power, aids in finemapping of associations and facilitates metaanalyses. Taqman genotyper software gives you the option of using userdefinable boundaries for data analysis or an improved algorithmic approach to automatically assign a genotype.
Genotype imputation for single nucleotide polymorphisms snps has been shown to be a powerful means to include genetic markers in exploratory genetic association studies without having to genotype them, and is becoming a standard procedure. Beagle is a state of the art software package for analysis of largescale genetic data sets with hundreds of thousands of markers genotyped on thousands of samples. If you use this beta version, please be sure to stop by the mach download page and fill out the. This is a list of notable software for haplotype estimation and genotype imputation.
It is designed to work on phased genotypes and can handle very large reference panels with hundreds or thousands of haplotypes. Free, secure and fast statistics software downloads from the largest open source applications and software directory. Ii reference data are available for download from the impute website. To convert imputation results of any imputation tools. A number of different software programs are available. Software tools institute for quantitative and computational.
The fimpute software is distributed as is solely for noncommercial use. The software performs genotype imputation and statistical tests for disease association, including single snp tests and regional multisnp tests. Genotype imputation is a powerful tool for increasing statistical power in an association analysis. Shapeit is a fast and accurate method for estimation of haplotypes aka phasing from genotype or sequencing data. Hibag is a state of the art software package for imputing hla types using snp data, and it relies on a training set of hla and snp genotypes. Genotype imputation is now an essential tool in the analysis of genomewide association scans. A flexible and accurate genotype imputation method for the. Comprehensive assessment of genotype imputation performance. Perhaps the reason that most people use of mach is to infer genotypes at untyped markers in genomewide association scans.
It is the companion software for a manuscript written by zhou and guan null distribution of bayes factors. Current software for genotype imputation citeseerx. Impute 4 implements the haploid imputation options included in impute 2, but is much faster and more memory efficient. Current software for genotype imputation human genomics. Fimpute efimpute was mainly developed for large scale genotype imputation in livestock where hundreds of thousands of. This pipeline takes genotype files, and adjusts the strand, the positions, the reference alleles, performs quality control steps and output a vcf file that satisfies the requirement for submittion to the sanger imputation service s. The process makes it relatively straightforward to combine results of genomewide association scans based on different genotyping platforms for two early examples of how the process works, see the papers by willer et al nat genet, 2008 and sanna et. A multiprocessor version, minimac2omp is available from the download page.
Genotypes for a relatively modest number of genetic. The default value is good for imputation but may be insufficient for phasing. Beagle is a tool for genotype calling, phasing, identitybydescent segment detection, and genotype imputation. Current software for genotype imputation pdf paperity. Genotype imputation for single nucleotide polymorphisms snps has been shown to be a powerful means to include genetic markers in exploratory genetic association studies without having to. This repository contains scripts to prepare plink genotype. Genotype imputation for genomewide association studies. Uk biobank genotyping and imputation data release march 2018. Impute increases accuracy and combines information across multiple reference panels while remaining computationally feasible. Imputation methods work by using haplotype patterns in a reference panel to predict unobserved genotypes in a study dataset, and a number of approaches have been proposed for choosing subsets of reference haplotypes that will maximize accuracy in a given. The figure illustrates the idea of genotype imputation in a sample of unrelated individuals. If the autocalling option is used for analysis, the software automatically analyzes the data and displays the data for each assay in a scatter plot that is colorcoded by. There are two datasets held at the ega the first for the genotyping data and the second for the imputation data. Summary an interface package for genotype imputation, phasing and computation of genotyping accuracy.
Genotype imputation approaches are likely to form a critical component of costefficient genomic selection programs to improve economically important traits in aquaculture. However, candidate gene studies can not use this method. Multiple imputation provides a useful strategy for dealing with data sets that have missing values. The formulas we have derived are a step toward the development of more complicated models that can be used to make practical quantitative predictions about imputation accuracy. Metaanalysis of multiple study datasets also requires a substantial overlap of snps for a successful association analysis, which can be achieved by imputation. A clustering methodology can be very useful to subgroup cattle for efficient genotype imputation. Premade human reference panels can be downloaded from the golden helix server by selecting download imputation data from within the project navigator. General imputation softwares to impute missing genotypes. Impute v2 attains higher accuracy than other methods when the hapmap provides the sole reference panel, but that the size of the panel constrains the improvements that can be made. Impute can also reduce the computation time and memory requirements, in this case by dividing larger chromosomes into smaller segments of several mega bases. Current software for genotype imputation springerlink. Fimpute software was used to carry out the imputation analyses. At the same time, the software can ignore haplotypes that are not helpful. Current software for genotype imputation david ellinghaus 1 stefan schreiber 1 andre franke 1 michael nothnagel 0 0 institute of medical informatics and statistics, christianalbrechts university, kiel, germany 1 institute of clinical molecular biology, christianalbrechts university, kiel, germany genotype imputation for single nucleotide polymorphisms snps has been shown to be a.
If you dont want to use docker, you can install the software packages by yourself step 1. When a hard genotype call is made, it carries with it a confidence score that corresponds to the likelihood that the called genotype was the correct choice. Genotype imputation in a sample of apparently unrelated individuals. Populationspecific genotype imputations using minimac or. Note that if pedigree information is provided fimpute makes use of this information for more accurate imputation. Jul 01, 2009 genotype imputation for single nucleotide polymorphisms snps has been shown to be a powerful means to include genetic markers in exploratory genetic association studies without having to genotype them, and is becoming a standard procedure. The mle and mldetails options request that mach should carry out maximum likelihood genotype imputation. Mach is a tool for genotype imputation and haplotyping using shotgun sequence data. High input genotype quality is the key for accurate imputation with fimpute. Uk biobank genotyping and imputation data release march. Imputation estimates genotypes at ungenotyped loci illumina.
To transform genotype data from the format of one imputation. It is computationally expensive in comparison to other gwas steps. Before genotype imputation, illumina recommends that research. Bayesian statistics for genetics imputation and software. Quality of imputed datasets is largely dependent on the software used.
Impute 5 is a genotype imputation method that can scale to reference panels with millions of samples. Owing to its ability to accurately predict the genotypes of untyped variants, imputation greatly boosts variant density, allowing finemapping studies of gwas loci and largescale metaanalysis across different genotyping. Genotype imputation michigan imputation server free genotype imputation service minimac3 computationally efficient implementation of mach algorithm for genotype imputation mach resolve long haplotypes or infer missing genotypes. Genotype imputation for genomewide association studies jonathan marchini and bryan howie abstract in the past few years genomewide association gwa studies have uncovered a large number of convincingly replicated associations for many complex human diseases. Imputation in genetics refers to the statistical inference of unobserved genotypes. Multiple imputation using sas software yang yuan sas institute inc. The genotype imputation analyses were performed using the alphaimpute v1. The basic steps of the pipeline is description in the diagram below. This program was used in the analysis of the 7 genomewide association studies carried out by the wellcome trust casecontrol consortium. A computer program for phasing observed genotypes and imputing missing genotypes. An excellent discussion of genotype imputation enables powerful combined analyses of genomewide association studies. A reference panel of 64,976 haplotypes for genotype imputation. Instead of lling in a single value for each missing value, a multiple imputation procedure replaces each missing value with a set of plausible values that represent the. It is achieved by using known haplotypes in a population, for instance from the hapmap or the genomes project in humans, thereby allowing to test for association between a trait of interest e.
Comparing performance of modern genotype imputation methods in. All of the imputation software had a weaker performance in low minor allele. In a scenario with 249 younger animals with ld genotypes study group and 658 older ones with 60k genotypes reference group, imputation accuracy was 63. Genotype imputation is a powerful tool for increasing statistical power in. The files can be downloaded as a full dataset or via individual file downloads, where the researcher can choose what tonot to download. Quality of imputed datasets is largely dependent on the software used, as well as the reference populations chosen.
Genotype imputation is particularly useful for combining results across studies that rely on different genotyping platforms but also increases the power of. The program is designed to work seamlessly with the output of our genotype imputation software impute and the programs qctool and gtool. Citeseerx current software for genotype imputation. The mach algorithm uses a markov chain approach and represents sampled chromosomes as.
Genotype imputation is a statistical technique that is often used to increase the power and resolution of genetic association studies. The mach algorithm uses a markov chain approach and represents sampled chromosomes as mosaics of each other. Mach, impute, beagle, bimbam into input files of software like. This method continues to refine the observation made in the impute2 method, that accuracy is optimized via use of a custom subset of haplotypes when imputing each individual. It achieves fast, accurate, and memoryefficient imputation by selecting haplotypes using. A variety of modern software packages are available for genotype imputation. There are currently 96 datafields in total ranging from 22000 22325 and you. Accuracy of genotype imputation in canadian yorkshire pigs. It was written to impute genotypes for the uk biobank dataset that consists of genetic data on 500,000 individuals.
Default value is 30 which is good enough for standard imputation tasks. Good quality genotypes were masked and reimputed by different imputation. This tutorials are not specific to your population of interest, but you can adapt them for your requirement. This technique allows geneticists to accurately evaluate the evidence for association at genetic markers that are not directly genotyped.
Genotype imputation software tools genomewide association. Beagle is a software package for phasing genotypes and for imputing ungenotyped markers. Citeseerx document details isaac councill, lee giles, pradeep teregowda. This page points to downloads, documentation, and papers for software that is written here at the center for statistical genetics. Let gij represent the genotype of individual iat snp jwith. Pdf current software for genotype imputation michael.
Genotype imputation to improve the costefficiency of. Plink, snptest and the genotype imputation tools mach, impute, beagle and bimbam. Anyone with approval for the 150,000 interim genotype data release has approval for the full release. Genotype imputation has been used widely in the analysis of gwa studies to boost. Genotype imputation enables powerful combined analyses of. Genotype imputation in studies of related individuals family samples constitute the most intuitive setting for genotype imputation. Genotypes for a relatively modest number of genetic markers can be used to identify long stretches of haplotype shared between individuals of known relationship. This is the fundamental basis of genotype imputation. Imputation attempts to predict these missing genotypes.
Genotype imputation has been widely adopted in the postgenomewide association studies gwas era. Owing to its ability to accurately predict the genotypes of untyped variants, imputation greatly boosts variant density, allowing finemapping studies of gwas loci and largescale metaanalysis across different genotyping arrays. Multiple imputation of genotype data below is a brief description of imputing genotype data for pedigree data including the data format. Current software for genotype imputation article pdf available in human genomics 34. Summary an interface package for genotype imputation, phasing and. Snptest, haploview, eigensoft and genabel, vcf, genotype data with count of allele genotype data with alleledose 6. Imputation is the prediction of missing genotypes, using. Panel a illustrates the observed data which consists of genotypes at a modest number of genetic markers in each sample being studied and of detailed information on genotypes or haplotypes for a reference sample.
Compare the best free open source statistics software at sourceforge. Raw sequencing reads were downloaded and aligned to the. Family samples constitute the most intuitive setting for genotype imputation. System requirements imputation is a computationally intense process. Testing for association at just these snps may not lead to a significant association b. Imputation provides a probability for each of the three possible genotype classes, and calls are based on the most likely genotype at each position9. Using minimac for genotype imputation involves two steps. The effect of reference datasets and software tools on. This protocol describes how to perform snp imputations for gwas metaanalysis with the genome of the netherlands reference panel using minimac or. Instead of filling in a single value for each missing value, a multiple imputation procedure replaces each missing value with a set of plausible values that represent the uncertainty about the.
Genotype imputation in studies of related individuals. A coalescent model for genotype imputation genetics. The effect of reference panels and software tools on. Imputation is likely to be run in the context of a gwas, studying population structure, and admixture studies. Frontiers evaluating the accuracy of imputation methods. I would like to point you to tutorials on how to use plink or mach or impute for genotype imputation, these tools widely used for this type of analysis. Pedigree information becomes more important as the low density panel becomes sparser. Fcgene can read and convert genotyped snp data having format of the software. A number of different software programs are available for genotype imputation, so the researcher must decide which program to use. Informally, most imputation methods phase the study genotypes at snps in t and look for perfect or near matches between the resulting haplotypes and the corresponding partial haplotypes in the reference panelhaplotypes that match at snps in t are assumed to also match at snps in u. Genotype imputation software tools genomewide association study data analysis genotype imputation has been widely adopted in the postgenomewide association studies gwas era. Novel methods for genotype imputation to wholegenome. To get mach, download one of the archives below and unpack it.