This is a list of notable software for haplotype estimation and genotype imputation. 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. A program for efficient genotype imputation impute 4 implements the haploid imputation options included in impute 2, but is much faster and more memory efficient. Interest of using imputation for genomic evaluation in. Plink, a tool for analyzing genotype phenotype data, snptest, a tool used for the analysis of single snp association in genomewide studies, and the genotype imputation tools like. List of haplotype estimation and genotype imputation software. A number of different software programs are available for genotype imputation, so the researcher must decide which program to use.
Genotype imputation in studies of related individuals family samples constitute the most intuitive setting for genotype imputation. Genotype imputation is a key step in the analysis of genomewide association studies. Sanger genotype imputation and phasing service is a webbased tool at wellcome sanger institute. A variety of modern software packages are available for genotype imputation relying on. The effect of reference datasets and software tools on. Select from the provided options or keep the defaults and select run.
Computations rely on efficient likelihood computations based on a hidden markov model hmm of haplotype diversity in. This is the fundamental basis of genotype imputation. Upcoming very large reference panels, such as those from the genomes project and the haplotype consortium, will improve imputation quality of rare and less common variants, but will also increase the computational burden. Genotype imputation is an important tool for genomewide association studies as it increases power, aids in finemapping of associations and facilitates metaanalyses. Quality of imputed datasets is largely dependent on the software used. Fcgene is a genotype format converter and can read and convert genotype snp data having the format of the software. There are a number of distinct scenarios in which genotype imputation is desirable, but the term now most often refers to the situation in which a reference panel of haplotypes at a dense set. High input genotype quality is the key for accurate imputation with fimpute. Current software for genotype imputation springerlink. The service currently offers the following reference panels. 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.
However, the cost of this snp chip is too high to genotype all selection candidates. See sanger imputation server stories, similar to uam. Our approach handles large pedigrees by using a markov chain monte carlobased program to infer inheritance vectors. Comparing performance of modern genotype imputation. 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 is a statistical technique that is often used to increase the power and resolution of genetic association studies. This page contains links to software packages that were developed by our group. This tutorials are not specific to your population of interest, but you can adapt them for your requirement. You may want to learn about new and improved minimac4 minimac is a low memory, computationally efficient implementation of the mach algorithm for genotype imputation. The software performs genotype imputation and statistical tests for disease association, including single snp tests and regional multisnp tests. Minimac3 is a lower memory and more computationally efficient implementation of the genotype imputation algorithms in minimac and minimac2. 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. An excellent discussion of genotype imputation enables powerful combined analyses. Hibaghla genotype imputation with attribute bagging the. This technique allows geneticists to accurately evaluate the evidence for association at genetic markers that are not directly genotyped. A flexible and accurate genotype imputation method for the. Genotype imputation traditionally is a procedure of inferring the small.
Mach, beagle, or provide specially designed file format conversion tools e. The service pipeline uses eagle2 or shapeit2 for prephasing, eagle2 for phasing, and pbwt positional burrowswheeler transform for genotype imputation. Gigi is a computer program to impute missing genotypes on pedigrees. Citeseerx document details isaac councill, lee giles, pradeep teregowda. Alternatively, the software can build new classifiers from training data supplied by. Gigi genotype imputation given inheritance introduction. Here, we demonstrate how the application of software engineering techniques can help to keep imputation broadly accessible. The function can also calculate rules for imputing each snp in a single dataset from other snps in the same dataset. Genotype imputation for genomewide association studies. Impute 5 a program for prephasing based genotype imputation based on the pbwt. Saykin, psyd2,3,4, and the alzheimers disease neuroimaging initiative adni 1regenstrief institute and indiana university school of medicine, indianapolis, in. A variety of modern software packages are available for genotype imputation relying on advanced concepts such as prephasing of the target dataset or. The effect of reference panels and software tools on genotype imputation kwangsik nho, phd1,2, li shen, phd2,3, sungeun kim, phd2,3, shanker swaminathan, btech2,4, shannon l.
Current software for genotype imputation citeseerx. Pdf current software for genotype imputation michael. Genotype imputation to improve the costefficiency of. David l morris1, patricia p ramsay2, kim e taylor3, lindsey a criswell3, tim j vyse1, glenys thomson4, lisa f. If you use impute 4 in your research, please cite the following publication. Good quality genotypes were masked and reimputed by different imputation frameworks. Genotype imputation is now an essential tool in the analysis of genomewide association scans.
Genotype imputation in families suppose a particular genotype g ij is missing genotype for person i at marker j consider full set of observed genotypes g evaluate pedigree likelihood l for each combination of g, g ij x posterior probability that g ij x is. A number of different software programs are available. 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 study. Comparing performance of modern genotype imputation methods in. Design of low density snp chips for genotype imputation in layer. 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. Applying it to genotype tissue expression gtex v6 rnaseq data imrep is able to efficiently extract tcr and bcr derived reads and accurately assemble the complementarity determining regions 3 cdr3s. Owing to its ability to accurately predict the genotypes. To create a reference panel, go to genotype create imputation reference panel from your quality filtered genotype spreadsheet. 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. Evaluating the accuracy of imputation methods in a five. 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. It is the companion software for a manuscript written by zhou and guan null distribution of bayes factors. Given two set of snps typed in the same subjects, this function calculates rules which can be used to impute one set from the other in a subsequent sample.
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. The genotype assembly will be included in the reference file, if add to reference panels folder is selected. Pedigree information becomes more important as the low density panel becomes sparser. Genotype imputation is a powerful tool for increasing statistical power in an. Perhaps the reason that most people use of mach is to infer genotypes at untyped markers in genomewide association scans. Hla genotype imputation with attribute bagging github. This technique allows geneticists to accurately evaluate the evidence for association at genetic. Genotype imputation enables powerful combined analyses of.
Minimac3 is designed to handle very large reference panels in a more computationally efficient way with no loss of accuracy. Note that if pedigree information is provided fimpute makes use of this information for more accurate imputation. Genotypes for a relatively modest number of genetic. Genotype imputation is the term used to describe the process of predicting or imputing genotypes that are not directly assayed in a sample of individuals. Imputation in genetics refers to the statistical inference of unobserved genotypes.
Genotype imputation has been widely adopted in the postgenomewide association studies gwas era. Genotype imputation methods and their effects on genomic. Citeseerx current software for genotype imputation. But to routinely implement this solution, the impact of imputation on genomic evaluation accuracy must be studied. Discriminative subgraph mining by learning from search. 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. Gedi is a software package which handles genotype data from unrelated individuals as well as individuals related by simple pedigrees such as trios. Summary an interface package for genotype imputation, phasing and computation of genotyping accuracy. Genotype imputation is particularly useful for combining results across studies that rely on different genotyping platforms but also increases the power of. Hibaghla genotype imputation with attribute bagging. It was written to impute genotypes for the uk biobank dataset that consists of genetic data on 500,000 individuals citation. Shapeit segmented haplotype estimation and imputation tool is a tool to estimate haplotypes. It is designed to work on phased genotypes and can handle very large reference panels with hundreds or thousands of haplotypes.
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