ELAI user manual
Contents
1. p 11 g example admix icm inp p 1 pos example hgdp chr22 pos s 20 C 2 c 10 o test mixgen 50 exclude nopos exclude miss1 This will generate four files with prefix test in a newly created subfolder output Using the R script r 2panel R one can plot the truth and the inferred local ancestries Both the command line for test run and a simple instruction to run the R script is in note txt 4 Input file formats The users should prepare genotype files for admixed cohort samples and training samples from source populations All genotype files assume the BIMBAM format 4 1 Genotype file format Genotypes should be for bi allelic SNPs all on the same chromosome The first two lines should each contain a single number The number on the first line indicates the number of individuals the number in the second line indicates the number of SNPs Optionally the third row can contain individual identifiers for each individual whose genotypes are included this line should begin with the string IND with subsequent strings indicating the identifier for each individual in turn Subsequent rows contain the genotype data for each SNP with one row per SNP In each row the first column gives the SNPs name which can be any string but might typically be a rs number and subsequent columns give the genotypes for each individual in turn Genotypes must be coded in ACGT while missing genotypes can be indicated by NN or 00 zero Exampl2. fit the page e Unless otherwise stated the options g p pos o etc are all case sensitive e There are three key parameters to specify number of upper clusters C number of lower clusters c and number of admixing generations mg Now we illustrate how to use ELAI through examples 1 A minimal example for two way admixture elai g source_popi txt p 10 g source_pop2 txt p 11 g admixed_pop txt g pop P g pop P g pop p 1 pos position_file txt s 30 o pref C 2 c 10 mg 10 The command line will run EM 30 steps uses 2 upper layer clusters and 10 lower layer clusters assuming number of admixture generation is 10 The output files will start with pref in the output directory 2 A more complicated example for three way admixture elai g source_pop1 txt p 10 g source_pop2 txt p 11 g source_pop3 txt p 12 g admixed_pop txt p 1 pos position_file txt s 30 o pref C 3 c 15 mg 20 exclude maf 0 01 exclude miss 0 05 exclude miss1 exclude nopos This command line takes three training samples of different ancestral source populations designated by p 10 p 11 and p 12 and one admixed samples designated by p 1 merge them based on the SNP position files A SNP will be excluded by ELAI if its minor allele frequency is lt 0 01 or its missing proportion is gt 0 05 or it is missed in one population or its position is not recorded in the position file ELAI will fit a model of 3 up
3. ELAI user manual Yongtao Guan Baylor College of Medicine Version 1 0 25 June 2015 Contents 1 Copyright 2 What ELAI Can Do 3 A simple example 4 Input file formats 41 Genotype file format srp 2 620 h gece we Gye amp Soar ee i ER OG pte ete oS 4 2 Phased genotype file format 2 0 0 02 ee ee 4 3 SNP position file format 2 0 0 0 0 000 a ee 5 Running ELAI 6 Output Files Gl Log files prefix Tog etek eh ae bok Ga Ge Ge i ae Be a a 6 2 SNP information file prefix snpinfo txt 000 6 3 Mean local ancestry dosage prefix ps21 txt 000 7 Choice of parameters Td Multipl EM Pun scrie a8 eae ep aed Be bes amp Sg Qe Oe ete ee Sc he tees 7 2 EM steps s and a fast linear approximation w 020 00005 8 Appendix A ELAI Options 9 Appendix B ELAI source code 1 Copyright ELAI Efficient local ancestry inference Copyright C 2014 2015 Yongtao Guan This program is free software you can redistribute it and or modify it under the terms of the GNU General Public License as published by the Free Software Foundation either version 3 of the License or at your option any later version This program is distributed in the hope that it will be useful but WITHOUT ANY WARRANTY without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE See the GNU General Public License for more details You should have received a copy of th
4. e GNU General Public License along with this program If not see http www gnu org licenses 2 What ELAI Can Do The software Efficient Local Ancestry Inference ELAI is developed and maintained by Yong tao Guan http www ncbi nlm nih gov pubmed 24388880 Please refer to the paper for the details of the statistical method The ELAI is designed to perform local ancestry inference for ad mixed individuals Comparing to existing methods to infer local ancestry ELAI has the following advantages e Directly works with diploid data no phasing required e No recombination map is required the recombination rates are implicitly estimated e It has a high resolution and can detect local ancestry track length of a few tenth of a centi Morgan cM e The new version can process an arbitrary number of admixed samples the previous version requires splitting a large sample into small subsets 3 A simple example Untar the downloaded file one finds a subfolder called example and executables elai mac for Mac OS X and elai lin for Linux In the subfolder those with suffix inp are input genotype files the one with suffix pos is the position file and the other two files truth and marker contain truth of the simulated admixture A R script named r 2panel R is included to plot the example runs One may perform a testing run using the following command line elai g example hap ceu chr22 inp p 10 g example hap yri chr22 inp
5. e Genotype file with 5 individuals and 4 SNPs 5 4 IND idl id2 id3 id4 id5 rsi AT TT AT AA rs2 GG CC GG CC CG rs3 CC CG GG rs4 AC CC AA AC AA Note that plink can convert genotype files from plink format to bimbam format The option is recode bimbam 4 2 Phased genotype file format By default ELAI assumes that the genotypes in the Genotype file are unphased If one has data where the phase information is known or can be accurately estimated e g from trio data as in the HapMap data then this can be specified by putting an sign at the end of the first line after the number of individuals In this case the order of the two alleles in each genotype becomes significant the first allele of each genotype should correspond to the alleles along one haplotype and the second allele of each genotype should correspond to the alleles along the other haplotype For example in the following input file the haplotypes of the first individual are AGCA and TCCC 5 4 IND idi id2 id3 id4 id5 rsi AT TT AT AA rs2 GC CC GG CC CG rs3 CC CG GG rs4 AC CC AA AC AA Note accidentally treating phased data as unphased has little harm except slower computation accidentally treating unphased panel as phased is very harmful Please make sure the genotypes are phased before you put sign 4 3 SNP position file format The file contains three columns the fir
6. ed For the upper layer number of clusters specified with C please use 2 for African American and 3 for Hispanics Other numbers is possible provided that you have the appropriate panel data sets But please be careful with the interpretation For the lower layer number of clusters specified with c a number 5 x C is recommended For the admixture generation specified with mg please use 10 for African American 20 for Hispanics and 100 for Uyghurs Other values of mixture generation can be used and the inferred local ancestry should be averaged 7 1 Multiple EM runs By default ELAI runs a single EM run It is recommended to run ELAI multiple times and average these results to achieve better estimates It is important to use R to specify a distinct random number seed for each run If R is omitted ELAI will use the machine time as the random seed But when multiple jobs are run simultaneously they may accidentally use the same random seed Thus R is highly recommended 7 2 EM steps s and a fast linear approximation w The number of EM steps is specified by s and s 20 is recommended This option fits the model using a quadratic algorithm which is accurate but slow We developed a fast linear approximation to the quadratic algorithm which is less accurate but fast One may try it to get a quick glimpse to the data but it is not yet recommended for serious studies The linear speed can be achieved using w 20 s 0 8 Appe
7. ndix A ELAI Options Unless otherwise stated arg stands for a string num stands for a number FILE I O RELATED OPTIONS g arg can use multiple times must pair with p p arg can use multiple times must pair with g arg takes integer values 1 10 11 12 pos arg can use multiple times arg is a file name o arg arg will be the prefix of all output files the random seed will be used by default EM PARAMETERS s step num specify steps in EM run C num specify number of upper clusters c num specify number of lower clusters mg num specify number of mixture generations R num specify random seed system time by default sem num save EM results to prefix em txt rem file read EM from a file OTHER OPTIONS v ver print version and citation h help print this help exclude maf num exclude SNPs whose maf is less than num default 0 exclude nopos exclude SNPs that has no position information exclude miss1 exclude SNPs that are missing in at least one file silence no terminal output 9 Appendix B ELAI source code If you want to compile an executable from the source code the first thing to do is to install a gsl library which can be obtained from http www gnu org software gsl Remember the path to which the gsl is installed and modify the Makefile the one in the src directory substituting the old path with the correct path Then you may type make to compile
8. per clusters and 15 lower clusters by running 30 EM steps The output files will start with pref 3 Use saved EM parameters elai g source_popi txt p 10 g source_pop2 txt p 11 g admixed_pop txt g pop P g pop P g pop p 1 pos position_file txt s 10 o pref C 2 c 10 mg 10 rem output pref em txt This command line will read EM parameters saved in the first example by default and continue to run 10 more steps 4 The population label p ELAI assigns each individual an integer to designate its population label The population label can be 0 1 9 10 11 12 The training samples are labelled as 10 11 12 with each number represents an ancestry It is important however that the labels for training samples start with 10 and do not skip an integer In other words if the number of ancestral populations is 2 then 10 and 11 will be used neither 10 and 12 nor 11 and 12 is valid Similarly if the number of ancestral populations is 3 then 10 11 and 12 will be used If p is followed by a valid integer then all individuals in the matching genotype file will be assigned a label of that integer The p can be followed by a filename then that file must contain the same number of entries as the number of individuals in the matching genotype file with one number occupying one row Finally an admixed cohort sample is labelled by 1 an un labelled training sample is labelled by 0 and an sample that is to be excluded is labelled b
9. st column is the SNP ID the second column is its physical location and the third column contains its chromosome number optional It is okay if the rows are unordered ELAI will sort the SNPs based on their position and chromosome number ELAI can take multiple position files as input and duplicate entries are acceptable If the genotype files contain SNPs across different chromosome ELAI will sort SNPs based on its chromosome and position However we recommend users to run ELAI chromosome by chromosome The following describes an example file where the delimit can be changed to rsi 1200 1 rs2 4000 1 rs3 3320 1 In certain applications one may insist on running multiple chromosomes together then the best practice is to stitch the position file together and add 100 000 000 unto the SNP positions with each chromosome swtich For example three lines in position file rs11 1200 1 rs22 2323 2 and rs33 3400 4 may become rs11 1200 99 rs22 100 002323 99 and rs33 200 003400 99 The 100 000 000 increment is because ELAI used prior such that 100 000 000 corresponds to 1 Morgan 5 Running ELAI First some general comments e ELAI is a command line based program The command should be typed in a terminal window in the directory in which ELAI executable exists e The command line should be all on one line the line break denoted by back slash in the example is only because the line is too long to
10. y 9 6 Output Files ELAI produces output files in a directory named output The directory will be created automati cally if it does not exist The names of the output files begin with prefix which can be specified by the o option We now describe the contents of these output files 6 1 Log file prefix log A log file contains the command line details of the progress and warnings generated When sending in a bug report it is important to include the log file as an attachment 6 2 SNP information file prefix snpinfo txt This file contains 6 columns with each SNP occupying a row The columns are rsID minor allele major allele minor allele frequency chromosome and position 6 3 Mean local ancestry dosage prefix ps21 txt This file contains the estimated ancestral allele dosages for each individual at each SNP This file contains N lines each admixed individuals occupies one line Each line contains S x M entries where S is the number of source populations and M is the number of markers Let j S x k s then j th column of a row is the k th SNP s ancestry allele dosage of the s th population This file has the same format for haploid and diploid individuals In R one may use the following commands to scan and partition the ancestral allele dosages gt yy scan output prefix ps21 txt gt dim yy c S M N 7 Choice of parameters For the EM steps specified with s a number between 20 and 50 is recommend
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