The OhmX platform is powered by an advanced informatics pipeline that supports both human whole genome variant discovery and variant verification analysis. Using onboard, real-time processing and powerful cloud computing, sample data is acquired and analyzed with just a few clicks and results are available the next day.
The OhmX platform creates whole genome maps by detecting sequence-specific tags, incorporated onto long DNA molecules. Electronic detection of tagged DNA molecules occurs as single DNA molecules pass through each of the nanochannels within the OhmX detector. Real-time signal processing tabulates the location of tags on each molecule and generates molecule records that include molecule length in milliseconds, location of tags in milliseconds, and other molecule and tag attributes that are used to assess the quality of reads.
Whole Genome Variant Discovery
Whole genome variant discovery analysis is performed by Human Chromosome Explorer™ (HCE). HCE is an advanced, cloud-based, whole-genome map assembly and structural variation (SV) analysis software for the OhmX platform. Developed by Hitachi High-Tech in collaboration with Nabsys, HCE uses Google Cloud Platform™. This High-Performance Computing infrastructure creates haplotype-aware, human whole-genome map assemblies and performs SV analysis with results visualized and reported through a web browser.
OhmX signal processed, calibrated, and filtered single molecule reads are de novo assembled by HCE into map contigs containing all labeled locations within the sample and are then aligned against a reference genome map. Shifts in the loci of the labels are indicative of shifts in the genome that serve as the basis for SV analysis.
The Results Summary View is the analysis dashboard which displays SV type and count in a pie chart and a global view of all chromosomes including electronic genome map coverage, known genes, and SV calls. From here users can launch a Circos Plot viewer.
HCE’s Circos Plot viewer showing a translocation on chromosome 2.
The Alignment Viewer shows all map contigs aligned to the reference of the selected chromosome. This interactive viewer displays more detailed information including map contig and SV size and location, molecule depth, selected interval size, and more.
The Assembly Viewer shows single molecule maps and how they align to create map contigs. This view shows label locations and molecule orientation, depth, coverage, and length.
Along with data encryption, Google Cloud Platform provides a cloud infrastructure with robust built-in compliance and security features applied to the physical datacenter, and the network. Hitachi has further built upon this infrastructure to create a secure platform for genomic data called the HCE Security Framework. Click here to learn more about HCE security.
Directed variant verification analysis is a hypothesis-based method to test for known SV types. This workflow is based on trained support vector machine (SVM) models to estimate the posterior probability of putative SVs.
First, a set of constructs representing the putative SVs is created. The constructs are assessed for uniqueness to ensure that any construct does not align to a region of the reference or another construct and are appended to the base reference so that molecules may either map to the source or to constructs. OhmX signal processed, calibrated, and filtered single molecule reads are directly aligned to either the reference or to constructs. Post-alignment analysis makes the SV calls for reads that align to a construct.
An example of the OhmX variant verification pipeline verifying a 3171bp homozygous insertion:
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Advance the understanding of disease, increase diagnostic yield, and improve patient outcomes by enabling routine, accurate, cost-effective analysis of genomic structural variation
