Converge Software

NGS reads are first mapped to nodes in PhyloTree and then realigned using a custom Smith–Waterman alignment algorithm that integrates PhyloTree and EMPOP information into the scoring function. Variants are called with reference to the rCRS. Additionally, the closest haplogroup is calculated, and variants are evaluated based on their occurrence in the haplogroup as well as other general metrics including frequency, strand bias, and coverage.

Forensic samples may contain DNA that is too degraded to generate an STR profile—or there may be an STR profile that does not generate a potential match in a national DNA databank. These samples may be analyzed with SNP markers, either Ancestry Informative Markers (AIMs) to generate an investigative lead or identity markers to associate a degraded crime scene sample to a known reference. Converge Software NGS Data Analysis module contains analysis parameters for generating reports from the Precision ID Ancestry Panel and the Precision ID Identity Panel.

Converge SNP analysis provides a variety of metrics to monitor sequencing quality, including coverage of aligned reads to a hotspot, strand bias, number of reads containing each base at the hotspot, genotype call, and quality.

Tertiary ancestry analysis consists of generating an estimation of admixture prediction from seven geographical regions: Africa, America, East Asia, Europe, Oceania, South Asia, and Southwest Asia, and population likelihoods (based on algorithms from Ken Kidd).

Identity analysis consists of calculating Random Match Probability (RMP) based on genotype frequencies generated from 1000 Genomes data as well as a Y haplogroup prediction.

Underlying the centralization of data creation, analysis, and storage to one easy-to-access location, the Converge Case Management module supports case, subject, genotype profile, and laboratory data management.

 The module serves the needs of various users such as laboratory managers and analysts, providing intuitive data views and reports that are configurable to the needs of each user and preserved for that user’s login. These features are easily accessible through a secured web browser under the protection of a laboratory’s IT department. The information management configurability allows the user to focus on pertinent information and adapts to a laboratory’s specific needs by enabling the addition of new data fields. Case data management includes metadata related to the case, subjects, DNA profiles, and attachments, with extensive data fields available to track all required information. Ideal for quickly reviewing case status and accessing case reports, the Case Dashboard functionality allows for an at-a-glance overview of the case. Extensive search and filtering capabilities on many data elements allow for faster access to relevant information, saving time and effort. Once performed, searches can be saved and viewed at a later date. Cases can also be exported for external sharing and storage and can be imported back as needed. Archiving cases can be scheduled or performed manually, allowing closed cases to be removed from the active dashboard. Should the need arise, archived cases can always be retrieved in the Case Dashboard.

Kinship and paternity testing can provide challenges in both the sheer volume of cases to be analyzed, as well as the complexity of laboratory workflows and statistical analyses being performed. The Converge Kinship and Paternity module offers a comprehensive set of parameters to perform analysis, allowing laboratories to conduct various types of relationship testing in a fraction of the time as compared to current methods.

The Kinship and Paternity module incorporates STR data analyzed by GeneMapper ID-X Software from capillary electrophoresis–based multiplex panels such as the Applied Biosystems VeriFiler Express PCR Amplification Kit and GlobalFiler Express PCR Amplification Kit, from the Converge NGS analysis of the Applied Biosystems Precision ID GlobalFiler NGS STR Panel v2. Converge Software identifies and processes Trio Paternity, Trio Maternity, Duo Fatherless, and Duo Motherless kinship tests by automatically creating cases, adding subjects and profiles, running analyses, and generating reports. Users can quickly and easily create a variety of hypotheses by drawing pedigree trees and setting comprehensive analysis parameters, including application of mutation models and population substructures. It also allows for genetic likelihood ratio calculations, as well as the generation of custom reports for any complex relationship analysis. These analyses are conducted utilizing validated algorithms.

Through an intuitive user interface, analysts can easily review detailed results, as well as generate and electronically sign reports in a few simple steps. Converge Software provides one default report template; however, laboratories can use existing tools to modify this template and adjust the report to their desired format. For trio and duo testing in paternity and maternity cases, Quick Kinship Analysis (KA) functionality from the Case Dashboard integrates all of these steps on one screen, saving time within the laboratory.

Complex analysis parameters used in kinship analysis require validation in order to determine the appropriate settings for the thresholds governing the data interpretation. Therefore, it is important that the software be tested using a variety of samples that challenge each different relationship-testing scenario. Although default settings are suggested within the software, these should be adjusted based on the outcome of each laboratory’s internal evaluation of Converge Software. Optimizing any software will require an additional investment on the part of the laboratory. Extensive system verification has been performed at Thermo Fisher Scientific, and a summary of these verification studies are available as a reference guide for users interested in implementing the software.