Clinical Validation of Sophia Genetics Assay

Next-generation sequencing (NGS) technologies have revolutionized the field of genomics, enabling rapid and cost-effective analysis of DNA and RNA . Among NGS methods, Illumina sequencing is the most widely used, due to its high-throughput and parallel sequencing capabilities. Nanopore sequencing, passes DNA through a nanopore, and the sequence is identified based on changes in electrical current. MGI's sequencing platforms use combinatorial probe-anchor synthesis technology to achieve high-throughput sequencing. These diverse NGS techniques have broad applications, including genome sequencing, metagenomics, and epigenetics, offering powerful tools for exploring genetic information.The main distinction between MGI and Illumina platforms lies in their methods for constructing and amplifying sequencing libraries. DNBSEQ™ utilizes circular single-stranded libraries with a central adapter, which are amplified by a rolling circle replication system to produce DNA nanoballs (DNBs). Each DNB then binds to a flowcell well via ionic bonds. Illumina technology employs linear double-stranded libraries with adapters at both ends, which are hybridized and amplified in clusters using bridge PCR. Both platforms use ordered flowcells and sequencing-by-synthesis methods. Thanks to its linear DNB amplification approach, where each replica is generated from the same original template, DNBSEQ™ technology eliminates detectable clonal amplification errors (specific to PCR) and index hopping, while also producing a very low rate of duplicated sequences. The MGI sequencer can accommodate two flowcells in parallel, each divided into four independent lanes. It is compatible only with MGI library preparation kits, while analysis pipelines developed for Illumina data are also compatible with MGI data.This study aims to compare the performance of MGI's DNBSEQ-G400 sequencing instrument with the gold-standard Illumina instruments (MiSeq and NextSeq 550) using the same DNA capture libraries constructed with Sophia Genetics assays. The goal is to assess whether MGI's platform is comparable to Illumina in profiling patients with solutions commercialized by Sophia Genetics.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Samples from patients with hereditary breast and ovarian cancer (HBOC), Lynch syndromes, and intestinal polyposis that will undergo genetic testing with commercial solutions provided by Sophia Genetics and sequenced on Illumina;
* Samples from patients with rare and hereditary disorders that have been profiled with commercial solutions provided by Sophia Genetics and sequenced on Illumina;
* Samples of patients for whom a report of the results is available;
* Samples of patients who have previously consented and are aware if their genomic results.

Exclusion Criteria:

* patients for whom blood, DNA or tissue samples are not available for analysis;
* samples that do not pass the quality check, set as DNA concentration, DNA integrity, library concentration and quality;
* samples for which consent for future analysis has not be given.