title: Exploring STR signal in the single- and multicopy number regimes: Deductions from an in silico model of the entire DNA laboratory process.
abstract: Short tandem repeat (STR) profiling from DNA samples has long been the bedrock of human identification. The laboratory process is composed of multiple procedures that include quantification, sample dilution, PCR, electrophoresis, and fragment analysis. The end product is a short tandem repeat electropherogram comprised of signal from allele, artifacts, and instrument noise. In order to optimize or alter laboratory protocols, a large number of validation samples must be created at significant expense. As a tool to support that process and to enable the exploration of complex scenarios without costly sample creation, a mechanistic stochastic model that incorporates each of the aforementioned processing features is described herein. The model allows rapid in silico simulation of electropherograms from multicontributor samples and enables detailed investigations of involved scenarios. An implementation of the model that is parameterized by extensive laboratory data is publically available. To illustrate its utility, the model was employed in order to evaluate the effects of sample dilutions, injection time, and cycle number on peak height, and the nature of stutter ratios at low template. We verify the model's findings by comparison with experimentally generated data.
authors.affiliation: Hamilton Institute, Maynooth University, Maynooth, Ireland.
authors.forename: Ken R
authors.initials: KR
authors.lastname: Duffy
authors.affiliation: Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Gurram
authors.affiliation: Biomedical Forensic Sciences, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Kelsey C
authors.initials: KC
authors.lastname: Peters
authors.affiliation: Biomedical Forensic Sciences, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Wellner
authors.affiliation: Biomedical Forensic Sciences, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Grgicak
mesh_terms: D000483:Alleles; D003198:Computer Simulation; D004247:DNA / Q000032:analysis*; D056915:DNA Copy Number Variations; D016172:DNA Fingerprinting; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity
chemical_list: D004247:DNA
keywords: Analytical threshold; Electropherogram signal model; Forensic DNA; Short tandem repeats; Single-copy DNA analysis