Advanced Strategies for DNA Identification

1. Yaniv Erlich@erlichya2/23/16
Advanced Strategies for
DNA Identification
@erlichya
Yaniv Erlich
Supported by NIJ 2014-DN-BX-K089

2. Yaniv Erlich@erlichya2/23/16
Outline
1. Surname inference from DNA
2. The power of genome-wide STR
profiles
3. Rapid identification with handheld
deice
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

3. Yaniv Erlich@erlichya2/23/16
Outline
1. Surname inference from DNA
2. The power of genome-wide STR
profiles
3. Rapid identification with handheld
deice
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

4. Yaniv Erlich@erlichya2/23/16
Correlation between Y-chr and surnames
www.ysearch.org:Y
Y
Smith
Smith
Y
Smith
Erlich
Advanced Strategies for DNA Identification
ACGCACGC…
Surname inference HipSTR Y-STRs MinION Summary

5. Yaniv Erlich@erlichya2/23/16
Databases of interest
www.smgf.org www.ysearch.org
140,000 publicly accessible surname-Ychr records
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

6. Yaniv Erlich@erlichya2/23/16
How to find surnames?
Estimating the time to most recent common ancestor
Target i-th record
in db
surname
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

7. Yaniv Erlich@erlichya2/23/16
Empirical test to determine the probability of
recovering a US surname
Y-chr of a
real person
Querying
Ysearch and
SMGF
Inferring
surname
x900
For US Caucasian males:
12% Successful recoveries
5% Wrong recoveries
83% Unknown
Comparing the predicted
surname to the true one
Surname inference
algorithm
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

8. Yaniv Erlich@erlichya2/23/16
Distribution of inferred surnames
Most of the inferred surnames are relatively
rare
Intro. Methodology The Venter case Anonymous datasets Summary
Inferred surname =~ zipcode
Advanced Strategies for DNA Identification

9. Yaniv Erlich@erlichya2/23/16
Putting it all together: the Venter case
www.ysearch.org:
lobSTR
DYS458: 17 repeats
Try it yourself: bit.ly/find_craig
We got a surname from whole
genome sequencing data
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

10. Yaniv Erlich@erlichya2/23/16
Aftermath
Our study
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

11. Yaniv Erlich@erlichya2/23/16
Outline
1. Surname inference from DNA
2. The power of genome-wide STR
profiles
3. Rapid identification with handheld
deice
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

12. Yaniv Erlich@erlichya2/23/16
HipSTR: a new STR calling algorithm
• Haplotype-based imputation, phasing, and genotyping of STRs
• Haplotype
– Robustness to stutter noise
• Imputation
– Recover STR dropouts from nearby SNPs.
• Phasing
– Resolve homoplasy between alleles
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

13. Yaniv Erlich@erlichya2/23/16
STR benchmarking results
HipSTR is the most accurate STR caller AND does this ~10x faster than the next best
method
50
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65
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100
Accuracy
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

14. Yaniv Erlich@erlichya2/23/16
HipSTR: solving homoplasy
• Can now correctly detect STRs with identical lengths but
different sequences (homoplasy)
• Real example:
– Length based genotype: -4/-4
– HipSTR genotype: (AGAT)8(ACAT)9 / (AGAT)10(ACAT)7
• HipSTR available at
https://github.com/tfwillems/HipSTR
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

15. Yaniv Erlich@erlichya2/23/16
Chromosome wide scan of Y-STRs
• Goal: scan every possible STR on the
Y chromosome and assess mutation
rates
• >200,000 transmissions = high
accuracy.
• Leverage 1500 whole genome world-
wide samples.
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

16. Yaniv Erlich@erlichya2/23/16
Benchmarking mutating rates
Our study
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

17. Yaniv Erlich@erlichya2/23/16
Deliveries
http://bit.ly/DOJERLICH
Scanning 4500 Y-STRs
Estimating mutation rates of
700 polymorphic Y-STRs
Finding additional fast
mutating Y-STRs
Imputation of Y-STRs with
high accuracy
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

18. Yaniv Erlich@erlichya2/23/16
Outline
1. Surname inference from DNA
2. The power of genome-wide STR
profiles
3. Rapid identification with handheld
deice
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

19. Yaniv Erlich@erlichya2/23/16
Oxford Nanopore MinION
Features:
• USB stick
• Portable
• Low throughput
• High error rate (10%)
Can we identify
samples within
minutes?
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

20. Yaniv Erlich@erlichya2/23/16
CODIS STR are challenging
1. MinION has too many indels
1. Many reads required to correct for
error
2. CODIS needs a PCR machine
Proposal:
Shotgun sequencing + Bayesian
approach
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

21. Yaniv Erlich@erlichya2/23/16
Approach
Real-time Sequencing data
(reads)
Filter SNPs
Bayesian algorithm
Based on prior knowledge
• Frequency alleles in
population
• Error rate
Alignment to human genome
15% error in base calling
Genome
db
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

22. Yaniv Erlich@erlichya2/23/16
Real experiment: me versus Venter
Probabilityofamatch
6m30s
• Assuming a
database of
107
• Retrospect
analysis
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

23. Yaniv Erlich@erlichya2/23/16
Real experiment: Venter vs. me
0%
1%
10%
100%
50
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550
600
650
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750
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1000
# of Reads Returned from MinION
P(Erlich)
P(Venter)
• Bad flowcell:
50min for
detection
• My genome:
23andMe
array
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

24. Yaniv Erlich@erlichya2/23/16
Summary
Advanced capabilities:
1. Surnames
2. Homoplasy detection
3. More Y-STRs
4. Imputation of missing markers
5. Rapid identification of DNA
Surname inference HipSTR Y-STRs MinION Summary
Advanced Strategies for DNA Identification

25. Yaniv Erlich@erlichya2/23/16
Acknowledgements
*Thomas Willems (MIT)
*Melissa Gymrek (HST – Harvard/MIT)
*Sophie Zaajier (Columbia University
*Robert Piccone (Columbia University)
Chris Taylor-Smith (Sanger Institute)
David Poznik (Stanford University)
1000Y analysis group
* Supported by: NIJ 2014-DN-BX-K089