Should I be dead?a very personal genomics

Neil Saunders

Digital Productivitywww.csiro.au

personal genomics: Slide 2 of 20

personal genomics pipelines

- we need reports that patients and clinicians can use

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personal genetics is already reality

http://genomesunzipped.org/2011/06/3747.php

personal genomics: Slide 4 of 20

introduction to 23andme

https://www.23andme.com

Who Should Have Access to Your DNA?

https://medium.com/backchannel/who-should-have-access-to-your-dna-6830fbf8dc79

personal genomics: Slide 5 of 20

data visualization at 23andme

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23andme “raw data”

rs4477212 1 82154 AArs3094315 1 752566 AArs3131972 1 752721 GGrs12562034 1 768448 GGrs12124819 1 776546 AArs11240777 1 798959 GGrs6681049 1 800007 CCrs4970383 1 838555 ACrs4475691 1 846808 CTrs7537756 1 854250 AG

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promethease + SNPedia

http://www.snpedia.com/index.php/Promethease

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ensembl variant effect predictor (VEP)

http://www.ensembl.org/info/docs/tools/vep/index.html

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converting 23andMe data to VCF

personal genomics: Slide 10 of 20

VCF conversion attempt #1 - 23andme2vcf.pl

https://github.com/arrogantrobot/23andme2vcf

in vcf 946 275not in reference 30 734DI 26DD 161II 689D 36I 112- - 13 752total 991 785in raw data 991 786

personal genomics: Slide 11 of 20

VCF conversion attempt #2 - plink

990 762 / 991 786 lines converted (but with issues)

sau103@spanxc-nh ˜/vep/data $ grep -v "ˆ#" vcf/plink19.vcf | head -4 | sort1 752566 rs3094315 A . . . . GT 0/01 752721 rs3131972 G . . . . GT 0/01 768448 rs12562034 G . . . . GT 0/01 776546 rs12124819 A . . . . GT 0/0

sau103@spanxc-nh ˜/vep/data $ grep -v "ˆ#" vcf/23andme2vcf.vcf | head -4 | sortchr1 752566 rs3094315 g A . . . GT 1/1chr1 752721 rs3131972 A G . . . GT 1/1chr1 776546 rs12124819 A . . . . GT 0/0chr1 798959 rs11240777 g . . . . GT 0/0

http://www.snpedia.com/index.php/User:Donwulff

personal genomics: Slide 12 of 20

VCF conversion attempt #3 - python script

(not tried)https://github.com/hammer/personal-genome-analysis/tree/master/scripts

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VCF conversion attempt #4 - bcftools

(not tried)http://samtools.github.io/bcftools/bcftools.html

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VCF conversion attempt #5 - the winner

973 306 / 991 786 lines converted

http://apol1.blogspot.com.au/2013/08/impute-apoe-and-apol1-with-23andme.html

#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT Neil_Saunders1 82154 rs4477212 A G . . . GT 0/01 752566 rs3094315 G A . . . GT 1/11 752721 rs3131972 A G . . . GT 1/11 768448 rs12562034 G A . . . GT 0/01 776546 rs12124819 A G . . . GT 0/0

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running the VEP - summary output

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parsing VEP output

you can read this later

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visualization of stop-gained variants

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clinical significance

benign

likely_pathogenic

not_provided

not_provided,not_provided

other

pathogenic

pathogenic,other

Genomic location of my stop_gained variants

personal genomics: Slide 18 of 20

so should I be dead?

yes and so should you“All genomes are dysfunctional: broken genes in healthy individuals”

“A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes”

http://genomesunzipped.org/2012/02/all-genomes-are-dysfunctional-broken-genes-in-healthy-individuals.php

http://www.sciencemag.org/content/335/6070/823.full

personal genomics: Slide 19 of 20

summary

a growing “hacker community” around personal genomics data

no shortage of inspiration for reporting and visualization tools

the challenge is interpretation for non-specialists