Internal validation of the fully continuous model in EuroForMix for its implementation in routine forensic DNA profiling

IF 3.6 2区医学 Q2 GENETICS & HEREDITY

Forensic Science International-Genetics Pub Date : 2026-06-01 Epub Date: 2026-02-26 DOI:10.1016/j.fsigen.2026.103460

J. González-Bao , A. Mosquera-Miguel , L. Casanova-Adán , A. Ambroa-Conde , A. Freire-Aradas , A. Cabrejas-Olalla , M. Boullón-Cassau , M. Palhares , J. Ruiz-Ramírez , A. Rodríguez-López , C. Phillips , M.V. Lareu , M. de la Puente

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引用次数: 0

Abstract

Despite being increasingly more common in the forensic routine, DNA mixtures still present an important roadblock in the analysis of genetic evidence. The International Society for Forensic Genetics (ISFG) recommends the use of the Likelihood Ratio (LR) in the statistical evaluation of the evidence for the contribution of a certain Person of Interest (POI). Numerous mathematical models have been developed for this purpose, which can be classified according to the information included: i) binary models only use the allelic information, ii) qualitative or semi-continuous models also accommodate drop-out and drop-in probabilities and iii) quantitative or fully continuous models include additionally allelic signal intensity (peak heights or read coverage). Before being implemented in the forensic routine, any software that supports a form of these models must be tested in different scenarios to perform an internal validation.

In this work we present the results of our internal validation of the fully continuous model present in EuroForMix (EFM) and DNAStatistX (used as control of EFM in this study), comparing its performance to the semi-continuous model in LRmix Studio. To do so, 59 artificial samples were prepared from 8 unrelated contributors in mixtures of 2, 3 and 4 contributors; besides, 19 tests from 7 real cases were run in both software. The following analyses were conducted: i) scrutiny of contributors in single-source serially diluted samples; ii) estimation of the percentage of contribution to the mixture; iii) comparison of results obtained in artificial mixtures for H1-True and H1-False hypotheses; iv) effect of sensitivity analysis in the final result; v) discrimination power of each model; vi) the behaviour of the Automatic Model Search option in EuroForMix and vii) comparison of results obtained in real casework analyses.

Our results show that EFM returns higher values than LRmix Studio both in single-source and mixed scenarios. The fully continuous model has demonstrated a neutral behaviour, returning inconclusive results when genetic evidence is scarce. If a reporting threshold is applied EFM is especially affected, with a higher proportion of negative log(LR) results turning inconclusive in comparison to LRmix Studio. Overall, EuroForMix has shown a correct performance, returning reliable results and reducing the subjectivity of the analysis.

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在EuroForMix中对其在常规法医DNA分析中实施的全连续模型进行内部验证。

尽管DNA混合在法医常规中越来越常见，但在遗传证据分析中仍然存在重要障碍。国际法医遗传学学会（ISFG）建议使用似然比（LR）对某一嫌疑犯（POI）的贡献进行证据的统计评估。为此已经开发了许多数学模型，可以根据所包含的信息进行分类：i)二元模型仅使用等位基因信息，ii)定性或半连续模型也考虑了辍学和辍学的概率，iii)定量或全连续模型还包括额外的等位基因信号强度（峰值高度或读取覆盖率）。在取证例程中实现之前，任何支持这些模型形式的软件都必须在不同的场景中进行测试，以执行内部验证。在这项工作中，我们展示了我们对EuroForMix （EFM）和DNAStatistX（在本研究中用作EFM的控制）中存在的全连续模型的内部验证结果，并将其性能与LRmix Studio中的半连续模型进行了比较。为此，从8个不相关的贡献者中制备了59个人工样本，分别为2、3和4个贡献者；此外，在两个软件中进行了7个实际案例的19个测试。进行了以下分析：i)对单源连续稀释样品中的贡献者进行审查；Ii)对混合物的贡献百分比的估计；iii)比较人工混合物中H1-True和H1-False假设的结果；Iv)灵敏度分析在最终结果中的影响；V)各模型的判别能力；vi) EuroForMix中自动模型搜索选项的行为和vii)在实际案例分析中获得的结果的比较。我们的结果表明，无论是在单源还是混合场景中，EFM都比LRmix Studio返回更高的值。完全连续模型表现出一种中性行为，在缺乏遗传证据的情况下返回不确定的结果。如果应用了报告阈值，EFM尤其会受到影响，与LRmix Studio相比，负对数（LR）结果的比例更高，结果变得不确定。总体而言，EuroForMix显示了正确的性能，返回了可靠的结果，减少了分析的主观性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Forensic Science International-Genetics 生物-医学：法

CiteScore

7.50

自引率

32.30%

发文量

132

审稿时长

11.3 weeks

期刊介绍： Forensic Science International: Genetics is the premier journal in the field of Forensic Genetics. This branch of Forensic Science can be defined as the application of genetics to human and non-human material (in the sense of a science with the purpose of studying inherited characteristics for the analysis of inter- and intra-specific variations in populations) for the resolution of legal conflicts. The scope of the journal includes: Forensic applications of human polymorphism. Testing of paternity and other family relationships, immigration cases, typing of biological stains and tissues from criminal casework, identification of human remains by DNA testing methodologies. Description of human polymorphisms of forensic interest, with special interest in DNA polymorphisms. Autosomal DNA polymorphisms, mini- and microsatellites (or short tandem repeats, STRs), single nucleotide polymorphisms (SNPs), X and Y chromosome polymorphisms, mtDNA polymorphisms, and any other type of DNA variation with potential forensic applications. Non-human DNA polymorphisms for crime scene investigation. Population genetics of human polymorphisms of forensic interest. Population data, especially from DNA polymorphisms of interest for the solution of forensic problems. DNA typing methodologies and strategies. Biostatistical methods in forensic genetics. Evaluation of DNA evidence in forensic problems (such as paternity or immigration cases, criminal casework, identification), classical and new statistical approaches. Standards in forensic genetics. Recommendations of regulatory bodies concerning methods, markers, interpretation or strategies or proposals for procedural or technical standards. Quality control. Quality control and quality assurance strategies, proficiency testing for DNA typing methodologies. Criminal DNA databases. Technical, legal and statistical issues. General ethical and legal issues related to forensic genetics.