High Density Electronic Maps To Verify Structural Variation in Human Genomes

Despite advances in next generation sequencing technologies, limitations imposed by short read length combined with sequence features such as polymorphism and copy number repeats present challenges for genomic assembly and... [ view full abstract ]

Despite advances in next generation sequencing technologies, limitations imposed by short read length combined with sequence features such as polymorphism and copy number repeats present challenges for genomic assembly and analysis. Longer range techniques such as optical mapping utilize long reads to provide information over a larger scale, but lack resolution and throughput.

To bridge the gap, Nabsys has employed its HD-MappingTM platform to construct long-range, electronic maps. The major advantages of electronic sensing are higher sensitivity, accuracy, scalability, and speed of detection. Using its electronic HD-Mapping platform, Nabsys has constructed whole human genome maps characterized by high depth of coverage as well as coverage of greater than 99% of the reference genome.

Nabsys SV-VerifyTM is a software package, which provides an efficient, robust pipeline for the systematic and automated evaluation of putative structural variants. SV-Verify utilizes unique Support Vector Machines (SVMs) tailored to different classes of structural variations (i.e. size, type and complexity) and provides a posterior probability for each putative structural variant.

We will describe SV-Verify training using reference material from the NIST Genome in a Bottle project, for a well-characterized human genome (NA12878) and show the resulting sensitivity and specificity of each SVM. We then present results obtained by applying SV-Verify to several thousand putative deletions in other human genomes.