Bayesdenovo - Revision history

Bingshan: /* Filtering */

2016-10-26T14:22:00Z

Filtering

← Older revision		Revision as of 10:22, 26 October 2016
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	http://genome.sph.umich.edu/wiki/Triodenovo		http://genome.sph.umich.edu/wiki/Triodenovo

	~~3. Further thoughts about filtering for SNVs without bam files (step 2 requires bam files). There is no consensus on filtering so this can be very flexible.~~
	* If you have a multi-sample call VCF it may be helpful to select those mutation candidates that appear only once in your VCF (AC=1 for example). This can be the top tier to consider. Relaxing AC to 2 or 3 can recover more real mutations but also increase false positives.
	* If it is too stringent to filter out known sites, it may be helpful to select candidates that have low (e.g. <0.002)1000G or ESP allele frequencies. Some mutations can occur on know variant sites but mutations with high population frequencies may not be of great interest, if indeed they are real.
	* Candidates in segmental duplications, low complexity regions or other copy number regions may be flagged for further analysis.
	* Candidates for which parents are not hom-ref or offspring is a double mutant are more likely to be due to artifacts so the interpretation of these candidates may require additional QC if they appear to be interesting to the investigators.

	== Download ==		== Download ==

Bingshan: /* Filtering */

2016-10-26T14:21:23Z

Filtering

← Older revision		Revision as of 10:21, 26 October 2016
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	== Filtering ==		== Filtering ==
	We recommend two filtering strategies. The first is a simple filtering and the second one is more ~~advance~~. Please see the triodenovo page below for more information:		We recommend two filtering strategies. The first is a simple filtering and the second one is more advanced. Please see the triodenovo page below for more information:

	http://genome.sph.umich.edu/wiki/Triodenovo		http://genome.sph.umich.edu/wiki/Triodenovo

Bingshan: /* Input files */

2016-10-25T19:51:29Z

Input files

← Older revision		Revision as of 15:51, 25 October 2016
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	** Note: In the VCF file either PL or GL has to be provided, and only the PL (or GL) field is used in the calling.		** Note: In the VCF file either PL or GL has to be provided, and only the PL (or GL) field is used in the calling.

	* A map file in the PLINK format. See blow for examples how to generate a high quality ~~map file.~~		* A map file in the PLINK format. See blow for examples how to generate a map file with common and high quality variants

	== Examples of generating the map file ==		== Examples of generating the map file ==

Bingshan: /* Input files */

2016-10-25T19:50:34Z

Input files

← Older revision		Revision as of 15:50, 25 October 2016
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	== Input files ==		== Input files ==
	* A ped file, with 5 colums [[http://www.sph.umich.edu/csg/abecasis/merlin/tour/ see merlin documentation]]. An example ped file is as follows		* A ped file, with 5 colums [[http://www.sph.umich.edu/csg/abecasis/merlin/tour/ see merlin documentation]]. An example ped file is as follows (Note that you can mix trios with other nuclear families in the same VCF file):
	quartet1 p1 0 0 1		quartet1 p1 0 0 1
	quartet1 p2 0 0 2		quartet1 p2 0 0 2
	quartet1 p3 p1 p2 1		quartet1 p3 p1 p2 1
			quartet1 p4 p1 p2 1
			nuc1 p5 0 0 1
			nuc1 p6 0 0 2
			nuc1 p7 p1 p2 1
			nuc1 p8 p1 p2 1
			nuc1 p9 p1 p2 1
			trio1 p10 0 0 1
			trio1 p11 0 0 2
			troi1 p12 p1 p2 1
			trio2 p13 0 0 1
			trio2 p14 0 0 2
			troi2 p15 p1 p2 1

	* A VCF file [[http://www.1000genomes.org/node/101 VCF specs]]. It can contain variant information for more individuals than in the ped file.		* A VCF file [[http://www.1000genomes.org/node/101 VCF specs]]. It can contain variant information for more individuals than in the ped file.

Bingshan at 16:38, 25 October 2016

2016-10-25T16:38:30Z

← Older revision		Revision as of 12:38, 25 October 2016
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	* A VCF file [[http://www.1000genomes.org/node/101 VCF specs]]. It can contain variant information for more individuals than in the ped file.		* A VCF file [[http://www.1000genomes.org/node/101 VCF specs]]. It can contain variant information for more individuals than in the ped file.
	** Note: In the VCF file either PL or GL has to be provided, and only the PL (or GL) field is used in the calling.		** Note: In the VCF file either PL or GL has to be provided, and only the PL (or GL) field is used in the calling.

			* A map file in the PLINK format. See blow for examples how to generate a high quality map file.

			== Examples of generating the map file ==
			* vcf2map: generate a sparse map file (see [[#Download\|Download]] for files genetic_map_GRCh37_chr1.txt and 1000G.SNV.clean.MAF0.05.tbl.gz)
			vcf2map --vcf input.vcf --ped input.ped --map genetic_map_GRCh37_chr1.txt --include_list 1000G.SNV.clean.MAF0.05.tbl.gz --out_map chr1.map

			* User defined r2 cutoff for LD pruning , min of average depth for filtering
			vcf2map --vcf input.vcf --ped input.ped --map genetic_map_GRCh37_chr1.txt --include_list 1000G.SNV.clean.MAF0.05.tbl.gz --max_r2 0.2 --min_avg_dp 2 --out_map chr1.r0.2.map

	== Output ==		== Output ==

Bingshan: /* Introduction */

2016-10-25T16:34:36Z

Introduction

← Older revision		Revision as of 12:34, 25 October 2016
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	== Introduction ==		== Introduction ==
	* The program '''bayesdenovo''' implemented a Bayesian framework for calling '''''de novo''''' mutations in '''nuclear families''' (including trios, quartets, and families with more siblings) for next-generation sequencing data.		* The program '''bayesdenovo''' implemented a Bayesian framework for calling '''''de novo''''' mutations in '''nuclear families''' (including trios, quartets, and families with more siblings) for next-generation sequencing data. If infers Identity-by-Descednt (IBD) allele sharing to increase the '''''de novo''''' mutation calling accuracy. As a result, the IBD sharing for the called '''''de novo''''' mutations is also available in the output file.
	* It takes as input a standard VCF file with PL or GL fields (storing genotype likelihoods). Commonly used callers, e.g. GATK and samtools, generate VCF files with PL values.		* It takes as input a standard VCF file with PL or GL fields (storing genotype likelihoods). Commonly used callers, e.g. GATK and samtools, generate VCF files with PL values.
	* It calculates the likelihood of the model with '''''de novo''''' mutations, denoted as L1, and the likelihood of Mendelian transmission, denoted as L0, and represent the '''''de novo''''' evidence using a Bayesian factor BF=L1/L0. In TrioDeNovo the '''''de novo''''' quality is represented as DQ=log10(BF) = log10(L1/L0).		* It calculates the likelihood of the model with '''''de novo''''' mutations, denoted as L1, and the likelihood of Mendelian transmission, denoted as L0, and represent the '''''de novo''''' evidence using a Bayesian factor BF=L1/L0. In TrioDeNovo the '''''de novo''''' quality is represented as DQ=log10(BF) = log10(L1/L0).

Bingshan at 16:30, 25 October 2016

2016-10-25T16:30:31Z

← Older revision		Revision as of 12:30, 25 October 2016
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	== Filtering ==		== Filtering ==
	We recommend two filtering strategies. The first is a simple filtering and the second one is more advance		We recommend two filtering strategies. The first is a simple filtering and the second one is more advance. Please see the triodenovo page below for more information:

	1. Basic filtering for SNVs. The following filter will retain sites of single nucleotides with only two alleles, QUAL>=30, and mutations in which parents are homozygous references and child is heterozygote with the heterozygote PL being zero, and the minimum PL of the other two genotypes in offering is 30 (i.e. the genotype likelihood, defined as P(R\|G) in which R represents the aligned bases and G is the underlying genotype, of the called het mutation is >1000 than the genotype likelihood of the other two genotypes). These filtering parameters can be tuned as needed in the following command.		http://genome.sph.umich.edu/wiki/Triodenovo

	less trio.vcf.out \| egrep "DQ\|#" \| perl -lane 'print if /#/; next if length($F[3])>1 \|\| length($F[4])>1 \|\| $F[4]=~/,/; next if $F[5]<30; $F[9] =~ /([A-Z])\/([A-Z])/; next if $1 ne $2; next if $F[10] !~ /$1\/$1/; $F[11]=~/([A-Z])\/([A-Z])/; next if $1 eq $2; $F[11] =~ /(\d+),(\d+),(\d+)/; next if $2 != 0 \|\| $1<30 \|\| $3<30; print' \| less

	~~2. Advanced filtering using a machine-learning approach (i.e. DNMFilter in the following webpage)~~

	http://~~humangenome~~.~~duke~~.edu/~~software~~

	3. Further thoughts about filtering for SNVs without bam files (step 2 requires bam files). There is no consensus on filtering so this can be very flexible.		3. Further thoughts about filtering for SNVs without bam files (step 2 requires bam files). There is no consensus on filtering so this can be very flexible.
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	== Download ==		== Download ==
	Source code of v0.05 [[Media:~~triodenovo~~.0.05.tar.gz \| download]] here.		Source code of v0.01 [[Media:bayesdenovo.0.01.tar.gz \| download]] here.

	== Contact ==		== Contact ==
	For questions please contact the authors (Bingshan Li: [mailto:bingshan.li@vanderbilt.edu bingshan.li@vanderbilt.edu])		For questions please contact the authors (Bingshan Li: [mailto:bingshan.li@vanderbilt.edu bingshan.li@vanderbilt.edu])

Bingshan: Created page with "== Update == v0.01 is available for download == Compilation == * After downloading the source code, unzip and untar it, and cd bayesdenovo, and then type Make..."

2016-10-25T16:25:59Z

Created page with "== Update == v0.01 is available for download == Compilation == * After downloading the source code, unzip and untar it, and cd bayesdenovo, and then type Make..."

New page

== Update ==
v0.01 is available for [[#Download | download]]

== Compilation ==
* After downloading the source code, unzip and untar it, and cd bayesdenovo, and then type Make
* If you encountered errors related to deprecated usage of some syntax please try to comment out the following in the core/Makefile
CXXFLAGS += -Werror -Wno-unused-variable -Wno-unused-result

== Introduction ==
* The program '''bayesdenovo''' implemented a Bayesian framework for calling '''''de novo''''' mutations in '''nuclear families''' (including trios, quartets, and families with more siblings) for next-generation sequencing data.
* It takes as input a standard VCF file with PL or GL fields (storing genotype likelihoods). Commonly used callers, e.g. GATK and samtools, generate VCF files with PL values.
* It calculates the likelihood of the model with '''''de novo''''' mutations, denoted as L1, and the likelihood of Mendelian transmission, denoted as L0, and represent the '''''de novo''''' evidence using a Bayesian factor BF=L1/L0. In TrioDeNovo the '''''de novo''''' quality is represented as DQ=log10(BF) = log10(L1/L0).
* DQ is the major parameter to control the output, along with others. See the [[#Output | example output ]] file below
* We recommend some basic and also a more advanced [[#Filtering | filtering]]

== Usage ==
A command without any input will invoke triodenovo and display the following message
*** This build (v.0.1) was compiled on Oct 25 2016, 11:16:22 ***
pedfile : (-pname)
datfile : (-dname)
mapfile : (-mname)

Additional Options
Input : --in_vcf [], --submap [1.00]
Denovo mutation parameters : --tstv_ratio [2.00], --minDQ [5.00]
Multi-threading : --nthreads [1]
Output : --out_prefix []

* Example 1: using default parameters

bayesdenovo -p sim.vcf.ped -d sim.vcf.dat -m sim.vcf.map --in_vcf sim.vcf --out_prefix sim.vcf.denovo

* Example 2: using --minDQ 7 to output de novo calls which are a minimum DQ of 7.
bayesdenovo -p sim.vcf.ped -d sim.vcf.dat -m sim.vcf.map --in_vcf sim.vcf --out_prefix sim.vcf.denovo --min_DQ 7

== Input files ==
* A ped file, with 5 colums [[http://www.sph.umich.edu/csg/abecasis/merlin/tour/ see merlin documentation]]. An example ped file is as follows
quartet1 p1 0 0 1
quartet1 p2 0 0 2
quartet1 p3 p1 p2 1

* A VCF file [[http://www.1000genomes.org/node/101 VCF specs]]. It can contain variant information for more individuals than in the ped file.
** Note: In the VCF file either PL or GL has to be provided, and only the PL (or GL) field is used in the calling.

== Output ==
* The output will be one file per family, and the prefix to the names is specified via --out_prefix

An example of output file is as follows

##fileformat=VCFv4.1
##ProgramStart=Tue Oct 25 11:20:39 2016
##BayesDeNovo=../bin/bayesdenovo -p sim.vcf.ped -d sim.vcf.dat -m sim.vcf.map --in_vcf sim.vcf --out_prefix sim.vcf.denovo
##Note=VCF file modified by polymutt2. Updated fileds include: QUAL, GT and GQ, and AC. NOTE: modification was applied only to biallelic variants
##FILTER=<ID=LOWDP,Description="Low Depth filter when the average depth per sample is lessn than 1">
##INFO=<ID=DP,Number=1,Type=Integer,Description="Total Read Depth">
##INFO=<ID=AF,Number=A,Type=Float,Description="Alternative Allele Frequency">
##INFO=<ID=AC,Number=1,Type=Integer,Description="Alternative Allele Count">
##INFO=<ID=FDQ,Number=1,Type=Integer,Description="Family-wise De Novo Mutatoin Quality in log10(BF) format">
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
##FORMAT=<ID=DQ,Number=1,Type=Integer,Description="De Novo Mutation Quality in log10(BF) format">
##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Read Depth">
##FORMAT=<ID=IV,Number=2,Type=Integer,Description="Best path inheritance vector. Founder alleles are arbiturally labeled (1 to 2*nFounders) and L1|L2 for non-founders indicated L1 and L2 from founders are transmitted">
##FORMAT=<ID=PL,Number=3,Type=Integer,Description="Phred-scaled Genotype Likelihoods">
#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT Rep1_1_1 Rep1_1_2 Rep1_1_3 Rep1_1_4
1 118 . C A 100 . AF=0.333333;AC=7;DP=1629;FDQ=8.667414 GT:DQ:DP:PL 0/0:.:202:1|2:0,100,255 0/0:.:234:3|4:0,100,255 0/1:8.97:203:1|3:100,0,255 0/0:.:206:2|4:0,100,255
1 858 . C A 100 . AF=0.333333;AC=10;DP=1592;FDQ=8.688325 GT:DQ:DP:PL 0/0:.:184:1|2:0,100,255 0/0:.:208:3|4:0,100,255 0/0:.:220:1|3:0,100,255 0/1:8.99:197:2|4:100,0,255

== Filtering ==
We recommend two filtering strategies. The first is a simple filtering and the second one is more advance

1. Basic filtering for SNVs. The following filter will retain sites of single nucleotides with only two alleles, QUAL>=30, and mutations in which parents are homozygous references and child is heterozygote with the heterozygote PL being zero, and the minimum PL of the other two genotypes in offering is 30 (i.e. the genotype likelihood, defined as P(R|G) in which R represents the aligned bases and G is the underlying genotype, of the called het mutation is >1000 than the genotype likelihood of the other two genotypes). These filtering parameters can be tuned as needed in the following command.

less trio.vcf.out | egrep "DQ|#" | perl -lane 'print if /#/; next if length($F[3])>1 || length($F[4])>1 || $F[4]=~/,/; next if $F[5]<30; $F[9] =~ /([A-Z])\/([A-Z])/; next if $1 ne $2; next if $F[10] !~ /$1\/$1/; $F[11]=~/([A-Z])\/([A-Z])/; next if $1 eq $2; $F[11] =~ /(\d+),(\d+),(\d+)/; next if $2 != 0 || $1<30 || $3<30; print' | less

2. Advanced filtering using a machine-learning approach (i.e. DNMFilter in the following webpage)

http://humangenome.duke.edu/software

3. Further thoughts about filtering for SNVs without bam files (step 2 requires bam files). There is no consensus on filtering so this can be very flexible.
* If you have a multi-sample call VCF it may be helpful to select those mutation candidates that appear only once in your VCF (AC=1 for example). This can be the top tier to consider. Relaxing AC to 2 or 3 can recover more real mutations but also increase false positives.
* If it is too stringent to filter out known sites, it may be helpful to select candidates that have low (e.g. <0.002)1000G or ESP allele frequencies. Some mutations can occur on know variant sites but mutations with high population frequencies may not be of great interest, if indeed they are real.
* Candidates in segmental duplications, low complexity regions or other copy number regions may be flagged for further analysis.
* Candidates for which parents are not hom-ref or offspring is a double mutant are more likely to be due to artifacts so the interpretation of these candidates may require additional QC if they appear to be interesting to the investigators.

== Download ==
Source code of v0.05 [[Media:triodenovo.0.05.tar.gz | download]] here.

== Contact ==
For questions please contact the authors (Bingshan Li: [mailto:bingshan.li@vanderbilt.edu bingshan.li@vanderbilt.edu])