Principles In Mixture Interpretation
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008DNA Mixture Interpretation:Principles and Practice in Component Deconvolution and Statistical AnalysisPrinciples in MixtureInterpretationAAFS 2008 Workshop #16Washington, DCFebruary 19, 2008John M. Butlerjohn.butler@nist.govOutline Elements of Mixture Interpretation ISFG Recommendations on Mixtures– UK Response– German mixture classification categories Flowchart to aid base/training/AAFS2008 MixtureWorkshop.htm1
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Elements of DNA Mixture InterpretationPrinciples (theory)Protocols (validation)Practice (training & experience)Two Parts to Mixture Interpretation Determination of alleles present in the evidenceand deconvolution of mixture componentswhere possible– Many times through comparison to victim and suspectprofiles Providing some kind of statistical answerregarding the weight of the evidence– There are multiple approaches and philosophiesSoftware tools can help with one or both of these AAFS2008 MixtureWorkshop.htm2
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Steps in the Interpretation of Mixtures(Clayton et al. 1998)Step #1Identify the Presence of a MixtureStep #2Designate Allele PeaksStep #3Identify the Number of PotentialContributorsClayton et al. (1998) Forensic Sci. Int. 91:55-70Step #4Estimate the Relative Ratio of theStep #5Consider All Possible GenotypeCombinationsStep #6Compare Reference SamplesIndividuals Contributing to the MixtureWill be covered in nextsection of workshop onmixture deconvolutionStatistical Approaches with MixturesSee Ladd et al. (2001) Croat Med J. 42:244-246 Inferring Genotypes of Contributors - Separate major and minorcomponents into individual profiles and compute the random matchprobability estimate as if a component was from a single source Calculation of Exclusion Probabilities - CPE/CPI (RMNE) – Theprobability that a random person (unrelated individual) would beexcluded as a contributor to the observed DNA mixture Calculation of Likelihood Ratio Estimates – Comparing theprobability of observing the mixture data under two (or more)alternative hypotheses; in its simplest form LR ning/AAFS2008 MixtureWorkshop.htm3
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008DAB Recommendations on StatisticsFebruary 23, 2000Forensic Sci. Comm. 2(3); available on-line dnastat.htm“The DAB finds either one or both PE or LRcalculations acceptable and stronglyrecommends that one or both calculations becarried out whenever feasible and a mixtureis indicated”– Probability of exclusion (PE) Devlin, B. (1992) Forensic inference from genetic markers.Statistical Methods in Medical Research, 2, 241–262.– Likelihood ratios (LR) Evett, I. W. and Weir, B. S. (1998) Interpreting DNA Evidence.Sinauer, Sunderland, Massachusetts.ISFG DNA Commissionon Mixture InterpretationGill et al. (2006) DNA Commission of theInternational Society of Forensic Genetics:Recommendations on the interpretation ofmixtures. Forensic Sci. Int. 160: ining/AAFS2008 MixtureWorkshop.htm4
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008UPDATED SLIDEAvailable for download from the ISFG ll et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: 90-101ISFG Recommendations on Mixture InterpretationJuly 13, 2006 issue of Forensic Science InternationalOur discussions have highlighted a significant need forcontinuing education and research into this ning/AAFS2008 MixtureWorkshop.htm5
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Summary of ISFG Recommendationson Mixture Interpretation1.The likelihood ratio (LR) is thepreferred statistical method formixtures over RMNE6. When minor alleles are the samesize as stutters of major alleles,then they are indistinguishable2.Scientists should be trained inand use LRs7. Allele dropout to explain evidencecan only be used with low signaldata3.Methods to calculate LRs ofmixtures are cited4.Follow Clayton et al. (1998)guidelines when deducingcomponent genotypes5.Prosecution determines Hp anddefense determines Hd andmultiple propositions may beevaluated8. No statistical interpretation shouldbe performed on alleles belowthreshold9. Stochastic effects limit usefulnessof heterozygote balance andmixture proportion estimates withlow level DNAGill et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: 90-101Responses to ISFG DNA CommissionMixture Recommendations UK Response– Gill et al. (2008) FSI Genetics 2(1): 76–82 German Stain Commission– Schneider et al. (2006) Rechtsmedizin 16:401-404 ENFSI Policy Statement– Morling et al. (2007) FSI Genetics 1(3):291–292 SWGDAM – nothing yet – a Mixture Interpretation subcommittee was started Jan ing/AAFS2008 MixtureWorkshop.htm6
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008UPDATED SLIDESWGDAM Mixture InterpretationSubcommittee Everyone not atJohn Butler (NIST) - chairevery meeting Gary Sims (CA DOJ) - co-chairMike Adamowicz (CT)Have met 3 times:Jack Ballantyne (UCF/NCFS)Jan 2007George Carmody (Carleton U)July 2007Cecelia Crouse (PBSO)Jan 2008Allison Eastman (NYSP)Roger Frappier (CFS-Toronto)Ann Gross (MN BCA)Additional Participants (Jan 2008)Phil Kinsey (MT)Bruce Heidebrecht (MD)Jeff Modler (RCMP)Steve Lambert (SC)Gary Shutler (WSP)Started in January 2007My perspective AAFS2008 MixtureWorkshop.htm7
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Elements of DNA Mixture InterpretationPrinciples (theory)ISFG RecommendationsSWGDAM GuidelinesProtocols (validation)Your LaboratorySOPsPractice (training & experience)Consistency across analystsTraining withinYour LaboratoryISFG (2006) Recommendations Recommendation 1: The likelihood ratio is thepreferred approach to mixture interpretation.The RMNE (probability of exclusion) approach isrestricted to DNA profiles where the profiles areunambiguous. If the DNA crime stain profile islow level and some minor alleles are the samesize as stutters of major alleles, and/or if dropout is possible, then the RMNE method may notbe conservative.Gill et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: ining/AAFS2008 MixtureWorkshop.htm8
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008UK ResponseGill et al. (2008) FSI Genetics 2(1): 76–82Recommendation 1: RMNE is a recognized and advocated interpretationmethod. The likelihood ratio and match probabilitymethods are interchangeable—however, the wording ofthe match probability is equally acceptable forunderstanding in court. In addition, a frequencycalculation can be used, e.g. ‘‘I have calculated that thechance of observing this combination of DNA markers isabout in 1 in X of the UK population’’ or ‘‘the chance thata person picked at random from the general UKpopulation would have this combination of DNA markersis about 1 in X’’.Recommendation 1 (cont): UK Response; Gill et al. (2008) FSI Genetics 2(1): 76–82If a profile can be identified with confidence from a mixture then the matchprobability statement may be preferable. A non-exhaustive list of examples isas follows:(a) There is a major/minor mixture where the major contributor can be easilyseparated from the minor contributor(s) by virtue of the differences in peakheight/area of the alleles.(b) It may be possible to condition on one contributor, e.g. a victim, and tosubtract this profile from the mixture, to leave a single contributor that canbe reported separately. The contributors may be even, or major/minor. If theevidential profile is not major then it is inevitable that the conditioned majorprofile will mask some of the minor contributor alleles. Consequently, if a matchprobability is reported, some of the minor contributor alleles will be masked bythe major contributor. The LR method may be preferred if this is the case.(c) When conditioning is used to subtract a profile, then this should bemade clear in the statement. If conditioning is challenged, then it may beappropriate to recalculate the strength of the evidence using the LR approach. Acaveat can be included in the statement to make this point ining/AAFS2008 MixtureWorkshop.htm9
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Example 1UK Response; Gill et al. (2008) FSI Genetics 2(1): 76–82If a profile can be identified with confidence from a mixture then thematch probability statement may be preferable.(a) There is a major/minor mixture where the major contributor can be easilyseparated from the minor contributor(s) by virtue of the differences in peakheight/area of the alleles.Major Contributor23: 1110 RFUs24: 1326 RFUs23,24majorminorMinor Contributor19,2519: 438 RFUs25: 523 RFUs523/1110 0.47 which isless than 0.60 PHRExample 2UK Response; Gill et al. (2008) FSI Genetics 2(1): 76–82If a profile can be identified with confidence from a mixture then thematch probability statement may be preferable.(b) It may be possible to condition on one contributor, e.g. a victim, and tosubtract this profile from the mixture, to leave a single contributor that can bereported separately.If Victim 11,12Then other componentwould be ning/AAFS2008 MixtureWorkshop.htm10
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008ISFG (2006) Recommendations Recommendation 2: Even if the legal systemdoes not implicitly appear to support the use ofthe likelihood ratio, it is recommended that thescientist is trained in the methodology androutinely uses it in case notes, advising the courtin the preferred method before reporting theevidence in line with the court requirements. Thescientific community has a responsibility tosupport improvement of standards of scientificreasoning in the court-room.Gill et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: 90-101UK ResponseGill et al. (2008) FSI Genetics 2(1): 76–82Recommendation 2: Accepted—albeit we prefer to think in terms ofadvising the justice system rather than the courtor e/training/AAFS2008 MixtureWorkshop.htm11
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008ISFG (2006) Recommendations Recommendation 3: The methods to calculatelikelihood ratios of mixtures (not consideringpeak area) described by Evett et al. (J. Forensic Sci.Soc. 1991;31:41-47) and Weir et al. (J. Forensic Sci.1997;42:213-222) are recommended.Gill et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: 90-101UK ResponseGill et al. (2008) FSI Genetics 2(1): 76–82Recommendation 3: All laboratories in the UK consider peakheight/area in their assessments. The formulaeare fundamental to all mixture interpretation withor without peak height/area base/training/AAFS2008 MixtureWorkshop.htm12
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008ISFG (2006) Recommendations Recommendation 4: If peak height or areainformation is used to eliminate variousgenotypes from the unrestricted combinatorialmethod, this can be carried out by following asequence of guidelines based on Clayton et al.(Forensic Sci. Int. 1998;91:55-70).Gill et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: 90-101UK ResponseGill et al. (2008) FSI Genetics 2(1): 76–82Recommendation 4: training/AAFS2008 MixtureWorkshop.htm13
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008ISFG (2006) Recommendations Recommendation 5: The probability of theevidence under Hp is the province of theprosecution and the probability of the evidenceunder Hd is the province of the defense. Theprosecution and defense both seek to maximizetheir respective probabilities of the evidenceprofile. To do this both Hp and Hd requirepropositions. There is no reason why multiplepairs of propositions may not be evaluated.Gill et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: 90-101UK ResponseGill et al. (2008) FSI Genetics 2(1): 76–82Recommendation 5: training/AAFS2008 MixtureWorkshop.htm14
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Thoughts by Peter Gill on Recommendation #5(ENFSI meeting, Krakow, Poland, April 19, 2007) Prosecution and defense each want to maximize their respective probabilities Recommendation 5 places ownership for each hypothesis. In order to perform the LR calculation(s), the forensic scientist decides on boththe prosecution and defense hypotheses. Since the forensic scientists usually cannot discover the defense hypothesisbefore the trial (as they are typically working with the prosecution if the DNAmatches ), assumptions must be clearly stated with the important caveat thatyou cannot perform calculations on the stand! (For example, you need threeweeks warning to make and check calculations.) By anchoring the respective hypotheses to each side, the defense can changetheir hypothesis but the prosecution does not need to change theirs It is worth noting that the likelihood ratio always goes up if the defense lowerstheir hypothesis (Hd gets lower with more possible combinations)ISFG (2006) Recommendations Recommendation 6: If the crime profile is amajor/minor mixture, where minor alleles arethe same size (height or area) as stutters ofmajor alleles, then stutters and minor allelesare indistinguishable. Under thesecircumstances alleles in stutter positions that donot support Hp should be included in theassessment. In general, stutter percentage is 15%Gill et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: ining/AAFS2008 MixtureWorkshop.htm15
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008NEW SLIDEConsideration of Peak in Stutter PositionMajor component allelesStutter,minor contributor,Minoror bothcontributorallele?Gill et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: 90-101UK ResponseGill et al. (2008) FSI Genetics 2(1): 76–82Recommendation 6: Stutters are locus-dependent It is recommended that laboratories make their ownmaximum experimentally observed stutter sizes perlocus determinations since the effects may be techniquedependent. It is recommended that [maximum stutter percentagesbe] evaluated per ining/AAFS2008 MixtureWorkshop.htm16
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008NEW SLIDEMeasured Stutter PercentagesVariable by Allele Length and CompositionTH01 9.3 allele: [TCAT]4 -CAT [TCAT]5Holt CL, Buoncristiani M, Wallin JM, Nguyen T, Lazaruk KD, Walsh PS. TWGDAM validation of AmpFlSTR PCR amplification kits for forensic DNAcasework. J Forensic Sci 2002; 47(1): 66-96.UK ResponseGill et al. (2008) FSI Genetics 2(1): 76–82 Characterization of 4 base stuttersWe agreed to review 4 bp stutters, however, we notethat their presence often relates to over-amplifiedsamples. Preliminary experimental work suggests thatthey are low level and generally less then 4% the sizeof the progenitor allele (Rosalind Brown, personalcommunication). Note that 4 bp and 4 bp stutter cannotbe distinguished from genetic somatic mutation withoutexperimental work—furthermore, somatic mutations maygive rise to peaks that are larger than those caused bystutter /training/AAFS2008 MixtureWorkshop.htm17
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008ISFG (2006) Recommendations Recommendation 7: If drop-out of an allele isrequired to explain the evidence under Hp: (S ab; E a), then the allele should be smallenough (height/area) to justify this. Conversely,if a full crime stain profile is obtained wherealleles are well above the background level, andthe probability of drop-out approaches Pr(D) 0,then Hp is not supported.Gill et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: 90-101UK ResponseGill et al. (2008) FSI Genetics 2(1): 76–82Recommendation 7: We recommend slight rewording [with mention ofcompanion allele] If a full crime-stain profile is obtained where alleles arewell above the background level, and the probability ofdropout Pr(D) approaches zero, then Hp is not supported(Figure ng/AAFS2008 MixtureWorkshop.htm18
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Hypothetical ExamplesGill et al. (2008) FSI Genetics 2(1): 76–82If Below Dropout Threshold Gill et al. (2008) FSI Genetics 2(1): aining/AAFS2008 MixtureWorkshop.htm19
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008If Above Dropout Threshold Gill et al. (2008) FSI Genetics 2(1): 76–82Setting Thresholds Detection (analytical) threshold– Dependent on instrument sensitivity 50 RFU– Impacted by instrument baseline noise Dropout (stochastic) threshold– Dependent on biological sensitivity 150-200 RFU– Impacted by assay and injection /training/AAFS2008 MixtureWorkshop.htm20
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Determining the Dropout (Stochastic) ThresholdGill et al. (2008) FSI Genetics 2(1): 76–82 The dropout threshold can be determined experimentallyfor a given analytical technique from a series of pre-PCRdilutions of extracts of known genotype technique (it willprobably vary between analytical methods). Thesesamples can be used to determine the point where allelicdropout of a heterozygote is observed relative to the sizeof the survivor companion allele. The threshold is themaximum size of the companion allele observed. This isalso the point where Pr(D) approaches zero (Fig. 4).Dropout threshold will change depending on instrument and assayconditions (e.g., longer CE injection will raise dropout threshold)ISFG (2006) Recommendations Recommendation 8: If the alleles of certain lociin the DNA profile are at a level that isdominated by background noise, then abiostatistical interpretation for these allelesshould not be attempted.Gill et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: ining/AAFS2008 MixtureWorkshop.htm21
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008UK ResponseGill et al. (2008) FSI Genetics 2(1): 76–82Recommendation 8: If there is a band below the experimental thresholdwhere background noise might be prevalent, and it isdistinct and clear from the background, then it should berecorded and available on the case file.ISFG (2006) Recommendations Recommendation 9: In relation to low copynumber, stochastic effects limit the usefulness ofheterozygous balance and mixture proportionestimates. In addition, allelic drop-out and allelicdrop-in (contamination) should be taken intoconsideration of any assessment.Gill et al. (2006) DNA Commission of the International Society of Forensic Genetics:Recommendations on the interpretation of mixtures. Forensic Sci. Int. 160: ining/AAFS2008 MixtureWorkshop.htm22
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008UK ResponseGill et al. (2008) FSI Genetics 2(1): 76–82Recommendation 9: Case pre-assessment is necessary in order to determinethe best scientific method to process a sample. Tofacilitate this, it is recommended that wherever possible,this should include quantification. Quantification is used todetermine the optimum method to process—if low-levelDNA, a sample would benefit from procedures to enhancesensitivity of detection. There may be reasons wherequantification is not practicable, especially if low levels ofDNA are expected, since the result itself may becompromised if a portion of the sample is sacrificed. At lowDNA levels, the accuracy of the quantification test itselfmay be inefficient.UK ResponseGill et al. (2008) FSI Genetics 2(1): 76–82Recommendation 9 (cont): It is possible that a given DNA profile may simultaneouslycomprise both ‘conventional’ and ‘low-level’ loci: forexample, if degradation has occurred then low molecularweight loci may be above the dropout threshold, whereashigh molecular weight loci may be below the dropoutthreshold. Similarly, if the sample is a mixture, then at a given locusthere may be some alleles that are above the dropoutthreshold (from a major contributor) and others that arebelow the dropout threshold (from a minor contributor), i.e.different interpretation rationale may be simultaneouslyapplied to different contributors within a ining/AAFS2008 MixtureWorkshop.htm23
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008German Stain Commission on DNA MixturesRechtsmedizin 2006, 16 : 401 - 404Article inGerman(Englishsummary inhandout)General recommendations of thestain commission on the interpretationof DNA results from mixed stainsSlide from Peter Schneider (presented at EDNAP meeting in Krakow in April 2007)Mixtures Mixed stain: more than two alleles per locus in at least twoDNA systems Inference on the number of contributors:– up to 4 alleles: at least 2 contributors– up to 6 alleles: at least 3 contributors– more than 6 alleles: no meaningful interpretation possibleSlide from Peter Schneider (presented at EDNAP meeting in Krakow in April ning/AAFS2008 MixtureWorkshop.htm24
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Adapted from Peter Schneider slide (presented at EDNAP meeting in Krakow in April 2007)Mixture Classification SchemeSchneider et al. (2006) Rechtsmedizin 16:401-404(German Stain Commission, 2006): Type A: no obvious major contributor, no evidence ofstochastic effects Type B: clearly distinguishable major and minorcontributors; consistent peak height ratios ofapproximately 4:1 (major to minor component) forall heterozygous systems, no stochastic effects Type C: mixtures without major contributor(s),evidence for stochastic effectsType AType BType CStochastic phenomena May lead to allele and locus drop-out and drop-in effects Occur when using „low copy number“ conditions– e,.g. with increased no. of PCR cycles,– BUT ALSO using standard conditions andDNA amounts 200pg (e.g. as minor component in a mixture!)Slide from Peter Schneider (presented at EDNAP meeting in Krakow in April ning/AAFS2008 MixtureWorkshop.htm25
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Stutter effects The following criteria have to be consideredin case of stutter peaks:– the relative stutter intensities within the allelesof a locus, as well as between loci of amultiplex amplification,– the possibility that a stain allele is in theposition of a stutter peak.Slide from Peter Schneider (presented at EDNAP meeting in Krakow in April 2007)Stutter effects In case of doubt a suspicious peak in theposition of a stutter band has to be consideredas a true allele and part of the DNA profile, andshould be included into the biostatisticalinterpretation.Slide from Peter Schneider (presented at EDNAP meeting in Krakow in April ning/AAFS2008 MixtureWorkshop.htm26
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Type of mixture and interpretation Type A: Mixed profile without stochastic effects, abiostatistical analysis has to be performed Type B: Profile of a major contributor can beunambiguously described and interpreted as a profilefrom an unmixed stain Type C: due to the complexity of the mixture, theoccurrence of stochastic effects such as allele and locusdrop-outs have to be expected:– a clear decision to include or exclude a suspect maybe difficult to reach, thus a biostatistical interpretationis not appropriate.Slide from Peter Schneider (presented at EDNAP meeting in Krakow in April 2007)Biostatistical approaches Calculation of the probability of exclusion for arandomly selectedstain donor* [P(E)](*RMNE - "random man not excluded") Calculation of the likelihood ratio [LR] based ondefined hypotheses for the origin of the mixedstainSlide from Peter Schneider (presented at EDNAP meeting in Krakow in April ning/AAFS2008 MixtureWorkshop.htm27
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Which approach should be used? If the basis for clearly defined and mutuallyexclusive hypotheses is given, i.e.:– the number of contributors to the stain can bedetermined,– unambiguous DNA profiles across all loci areobserved (type A mixtures, or type B, if the personconsidered as "unknown" contributor is part of theminor component of the mixture),then the calculation of a likelihood ratio isappropriate.Slide from Peter Schneider (presented at EDNAP meeting in Krakow in April 2007)Which approach should be used? If major/minor contributors cannot be identified based onunambiguous DNA profiles, or if the the number ofcontributors cannot be determined, then the calculationof the probability of exclusion is appropriate. The calculation of P(E) is always possible for type A andtype B mixtures.Slide from Peter Schneider (presented at EDNAP meeting in Krakow in April ning/AAFS2008 MixtureWorkshop.htm28
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008Not acceptable is the inclusion of a genotype frequency of anon-excluded suspect into the report, if the givenmixed stain does not allow a meaningfulbiostatistical interpretation.– this would lead to the wrongful impression that thisgenotype frequency has any evidentiary valueregarding the role of the suspect as a contributor tothe mixed stain in question.Slide from Peter Schneider (presented at EDNAP meeting in Krakow in April 2007)Conclusions The likelihood ratio has a significant weight of evidence,as it relates directly to the role of the suspect in thecontext of the origin of the stain. The exclusion probability makes a general statementwithout relevance to the role of the suspect. However, this does not imply that P(E) is always more"conservative" in the sense that the weight of evidence isnot as strong compared to the LR.Slide from Peter Schneider (presented at EDNAP meeting in Krakow in April ning/AAFS2008 MixtureWorkshop.htm29
Mixture Interpretation Principles – J.M. ButlerFebruary 19, 2008GEDNAP 32Mixture interpretation exercise: 3 person mixture without major contributor Person A from group of reference samples wasnot excluded Allele frequencies for eight German databasesystems provided for exercise German-speaking GEDNAP participants invitedto participate based on publishedrecommendationsSlide from Peter Schneider (presented at EDNAP meeting in Krakow in April 2007)GEDNAP 32Results: 22 labs submitted results (from approx. 80German-speaking GEDNAP participants) Calculations submitted were all correct andconsistent:– 15x LR approach: Person A 2 unknown vs. 3 unknown contributors– 11x RMNE calculation Will be offered again next timeTraining and Specific Guidelines/Classification Schemesyielded consistent results among laboratoriesSlide from Peter Schneider (presented at EDNAP meeting in Krakow in April ning/AAFS2008 MixtureWorkshop.htm30
Mixture Interpretation Principles – J.M. ButlerDefine what isMIXTUREa mixture( 2 alleles at 2 loci ) 2 allelesNOat a locus,February 19, 2008CLASSIFICATION FLOWCHARTDeveloped by John Butlerbased on German classificationsSchneider et al. (2006) Rechtsmedizin 16:401-404Single SourceDNA Sampleexcept triallelics?LikelihoodRatio [LR]Determine STR profileand compute RMPYESYESProbability ofExclusion [PE]“RMNE”Mixed DNASampleNOAre # ofcontributorsdefined?YESStochasticEffects ?Possible LowLevel DNA) ?NODifferentiate aMajor/MinorComponent?YESAssume #Contributors?Define reliableratio ranges(4:1 to 10:1)YESNODefine LCNlimits ( 200 pg)TYPE BTYPE CDetermine component profile(s)and compute RMP for majorA biostatistical analysisshould not be performedTYPE AA biostatistical analysismust be performedClaims Have Been Made of No ConsensusRegarding Mi
Flowchart to aid interpretation. Mixture Interpretation Principles – J.M. Butler February 19, 2008 . Calculation of Exclusion Probabilities - CPE/CPI (RMNE) – The . (UCF/NCFS) George Carmody (Carleton U) Cecelia Crouse (PBSO)
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