22
DNA MIXTURES: CHALLENGES WITH INTERPRETATION

DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

  • Upload
    others

  • View
    11

  • Download
    0

Embed Size (px)

Citation preview

Page 1: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

DNA MIXTURES: CHALLENGES WITH INTERPRETATION

Page 2: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

Issues with mixture interpretation

PCASTSimple v. Complex mixtures Issues with Complex mixturesHow has forensic community dealt with

complex mixturesPresent/Future

Page 3: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

PCAST

Page 4: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

PCAST contrasts simple and complex mixtures

Simple* Complex*

Sometimes sex cases are complex and touch items simple, so…

Page 5: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier
Page 6: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

6

Page 7: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

Figuring out genotypes, not just alleles

A B

Page 8: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

Mixture Deconvolution

A BC D

Page 9: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

Complex Mixtures 9

Does A go with B? With C? With D?

Or is it a homozygote?

A B C D

Page 10: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

DBAFC

E

Page 11: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

Number of Contributors

Page 12: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

Stochastic Effects

Low Template DNA

Drop-Out

Drop-In

Stutter

Source: John Butler, Advanced Topics in Forensic DNA Typing: Methodology (pg. 325)

Page 13: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

13

DROP IN DROP OUT

Page 14: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

Stutter

John Butler, Forensic DNA Typing: Interpretation Elsevier (2015) p. 75

Page 15: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

Degradation

Page 16: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

16

Page 17: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

More Complex Modelling

Less binary modeling (CPI), more semi-continuous and continuous programs

Page 18: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

Modelling Software ValidationHow stochastic effects/artifacts are modelled

Different drop-out ratesDifferent drop-in ratesStutter

Use of peak heights# of contributorsRelatednessDegradationHow low is too low

How program codedHow software is maintained

Lab environments are differentDifferent validation –quality?

Differences in Prob Gen Programs

Page 19: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

Probabilistic Genotyping

Assumptions program is making in generating its likelihood ratio in your case

(what are the hypotheses?; # of contributors? Related/unrelated?)

Who else fits into the mixture? Would the judge/you/juror #5 have a LR>1?

19

Page 20: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

OCME interpretation

is it a mixture? meet concordance policy? (dupe rule) estimate the number of contributors what is the mixture ratio

If 1:1 can’t deconvolute (FST here we come) Rules for assigning alleles (heterozygote vs. homozygote) to a

deduced profile

https://nycocme.qualtraxcloud.com/ShowDocument.aspx?ID=1148

suitable for comparison?Look at how many peaks, peaks below threshold, quality of data

Page 21: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier

Inconclusive: too many alleles

Page 22: DNA MIXTURES: CHALLENGES WITH INTERPRETATION Mixtures - Challenges with... · Low Template DNA Drop-Out Drop-In Stutter ... John Butler, Forensic DNA Typing: Interpretation Elsevier