taming uncertainty in forensic dna evidence · dna samples. journal of forensic sciences, 2001....

Cybergenetics © 2007-2011 1

Taming Uncertainty inForensic DNA Evidence

ENFSI MeetingENFSI MeetingApril, 2011April, 2011

Brussels, BelgiumBrussels, Belgium

Mark W Mark W PerlinPerlin, PhD, MD, PhD, PhD, MD, PhDCybergenetics, Pittsburgh, PACybergenetics, Pittsburgh, PA

Cybergenetics © 2003-2011Cybergenetics © 2003-2011

Uncertainty

•• people (and the law) want people (and the law) want certaintycertainty•• scientific data are scientific data are uncertainuncertain

•• probabilityprobability describes uncertainty describes uncertainty•• informationinformation is is a change in probabilitya change in probability

•• DNA identification is an information science DNA identification is an information science•• goal is goal is maximal objective informationmaximal objective information

Genotype

?

Prior probabilityPrior probability

10, 1010, 1110, 1210, 1311, 1111, 1212, 1313, 13 …

unknown personpopulation


Genotype

?

Likelihood functionLikelihood function

10, 1010, 1110, 1210, 13biological father

child

mother

Genotype

?10, 1010, 1110, 1210, 13

Posterior probabilityPosterior probability

Objective Bayesian inference posterior = prior x likelihood

biological father

child

mother

Match

?10, 1010, 1110, 1210, 13 Pr(matching genotype)

10, 11

biological father

child

mother

putative father

50%


Match

?10, 1010, 1110, 1210, 13

10, 1010, 1110, 1210, 1311, 1111, 1212, 1313, 13 …

Pr(matching genotype)

Pr(cooincidental genotype)

10, 11

50%

5%

biological father

child

mother

putative father

population

InformationPr(matching genotype)

Pr(cooincidental genotype)LR =

Likelihood ratioLikelihood ratio

log(LR) is a standard measure of information

50%5%

= 10=

log10(10) = 1 information unit

MW Perlin. Explaining the likelihood ratio in DNA mixture interpretation. Proceedingsof Promega's 21st International Symposium on Human Identification, 2010.

Kinship

?10, 1010, 1110, 1210, 13

10, 1010, 1110, 1210, 1311, 1111, 1212, 1313, 13 …



10, 11

missing person

son

spouse

daughter

father

biological remains

90%

5%population


Phenotype

+

evidence

reality

PhenotypeLab

+

10 11 12

evidence STR data

reality observation

Phenotype

evidence STR data genotype

10 11 12

10, 10 @ 30%10, 11 @ 50%10, 12 @ 20%

Lab Infer

+

reality observation model


Phenotype

?10, 1010, 1110, 1210, 13

10, 1010, 1110, 1210, 1311, 1111, 1212, 1313, 13 …



10, 11

50%

5%

evidence

suspect

population

10 11 12

Computer Interpretation

• quantitative computer interpretation• statistical search of probability model• preserve all identification information• objectively infer genotype, then match

• any number of mixture contributors• stutter, imbalance, degraded DNA• calculate uncertainty of every peak

Quantitative Data


Quantitative Interpretation

Perlin MW, Szabady B. Linear mixture analysis: a mathematical approach to resolving mixedDNA samples. Journal of Forensic Sciences, 2001.

Calculate Peak Uncertainty

MW Perlin, A Sinelnikov. An information gap in DNA evidence interpretation. PLoS ONE, 2009.

Infer Accurate Genotype

MW Perlin, MM Legler, CE Spencer, JL Smith, WP Allan, JL Belrose, BW Duceman.Validating TrueAllele DNA mixture interpretation. Journal of Forensic Sciences, 2011.


Qualitative Thresholds

Over threshold,peaks are treatedas allele events.

Under threshold,alleles do not exist.

list ofincluded alleles

Qualitative Method VariationNational Institute of Standards and Technology

Two Contributor Mixture Data, Known Victim

31 thousand (4)

213 trillion (14)

Fingernail: 7% MixtureCommonwealth v. Foley

Score Method13 thousand inclusion

23 million use victim189 billion quantitative

• probability modeling preserves information• peak threshold discards information

The DNA Investigator™ Newsletter, 2009Same Data, More Information – Murder, Match and DNA


More Data, More Information

• low template mixture• three DNA contributors• triplicate amplification• post-PCR enhancement

vWA locus data

• no match score found• computer interpretation• joint likelihood function

Information

Gen

oype

pro

babi

lility

(vW

A)

Assume theta = 1%, and three contributors. A match between the suspect and the evidenceis 3,620,000 times more probable than coincidence.

6x

More Data, More Information

33

4455

66

Perlin MW, Greenhalgh M. Scientific combination of DNA evidence: a handgun mixture ineight parts. Twentieth International Symposium on the Forensic Sciences of the Australian

and New Zealand Forensic Science Society, Sydney, Australia. 2010.


Data: Locus D18

33

44

55

66

11

22

44

88

Preserve vs. Discard

MW Perlin, A Sinelnikov. An information gap in DNA evidence interpretation. PLoS ONE, 2009.



7.03 7.03

6.24 6.2413.2613.26

Quantitative InterpretationQuantitative Interpretation

Inclusion methodInclusion method


Validated Reproducibility

0

5

10

15

20

25

2A 2C 2H 2D 2B 2F 2G 2E

log(L

R)

Rep 1

Rep 2

0.1750.175



• quantitative interpretation preserves information - every time• peak threshold discards information - 70% of the time

Perlin MW, Duceman BW. Profiles in productivity: greater yield at lower cost with computerDNA interpretation. Twentieth International Symposium on the Forensic Sciences of the

Australian and New Zealand Forensic Science Society, Sydney, Australia. 2010.


Data Peak Height is a RandomVariable with Mean and Variance

Accurate vs. DispersedGenotype Probability

Missed Allele Error > 100%

Threshold = 200 rfu

0.00

0.25

0.50

0.75

1.00

1.25

1.50

1.75

50:50 30:70 10:90

DNA mixture ratio

Fals

e n

eg

ati

ve r

ate

(all

ele

s/

locu

s)

1000 pg

500 pg

250 pg

125 pg

Perlin MW. Reliable interpretation of stochastic DNA evidence.Canadian Society of Forensic Sciences 57th Annual Meeting; Toronto, ON. 2010.


Investigative DNA Database10, 1010, 1110, 1210, 13

evidence genotypes suspect genotypes

LR

• genotype probability representation (not alleles)• fully preserves DNA identification information• enables LR calculation with every match

10, 1010, 1110, 1210, 13

• connect crimes to criminals• disaster victim identification (WTC)• find missing people• automatic familial search• combat terrorism through DNA

MW Perlin, JB Kadane, RW Cotton. Match likelihood ratio for uncertain genotypes.Law, Probability and Risk, 2009.

Societal Consequences• much informative DNA evidence goes unused• lost in "interim" qualitative interpretation methods, thresholds applied for analyst convenience• DNA databases (e.g., CODIS) lose information, using inclusion-based "alleles", instead of ISFG's preferred LR-based "genotype" probability

Inaccurate, uninformative DNA interpretation:• DNA analysts lose genotypes • prosecutors lose criminal cases• databases lose investigative leads • innocent law abiding citizens lose lives

The DNA Investigator™ Newsletter, 2011DNA Intelligence and Forensic Failure – What you don't know can kill you

International Consensus1. DNA data is continuous, and has random variation2. Thresholds do not work for low template DNA3. Mathematical models can account for random variation

4. The 21st century might be a good time to move awayfrom potentially biased human review of low level (oralmost any) DNA data to some sort of objectivecomputer interpretation that can infer genotypes up toprobability, without ever looking at suspects, that givessome (possibly uninformative) objective answer.

M Perlin; P Gill, J Buckleton, B Budowle, A van Daal. Low template DNA controversy.Twentieth International Symposium on the Forensic Sciences of the Australian and New

Zealand Forensic Science Society, Sydney, Australia. 2010.


Strengthening Forensic Science

http://www.cybgen.com/[email protected]

•• objective, reliable, consistent interpretation objective, reliable, consistent interpretation•• preserve all available information, preserve all available information, from the scene of crime tofrom the scene of crime to courtcourt

•• probabilistic genotypesprobabilistic genotypes•• modern statistics and computation modern statistics and computation•• solid mathematical foundation solid mathematical foundation

•• platinum standard for preserving DNA information platinum standard for preserving DNA information•• move beyond less informative interim methods move beyond less informative interim methods

Learning More

www.cybgen.com/information

• Newsletters gentle introduction to ideas• Courses for scientists and lawyers• Presentations handouts, movies, transcripts• Publications abstracts, manuscripts

The science of quantitative DNA mixture interpretation

taming uncertainty in forensic dna evidence · dna samples. journal of forensic sciences, 2001....

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