BioProject

At present, the identification of genomic regions involved in Copy number variants/alterations (CNVs/CNAs) is performed with microarray platforms or by exploiting data generated by second generation sequencing (SGS) technologies. More...

At present, the identification of genomic regions involved in Copy number variants/alterations (CNVs/CNAs) is performed with microarray platforms or by exploiting data generated by second generation sequencing (SGS) technologies. However, although these technologies allow to detect alterations at a genome-wide level with high accuracy, both microarray and SGS techniques are based on very long and complex experimental recipes that require several days, or even weeks, to obtain results. The past few years have seen the emergence of nanopore-based sequencing technologies which interrogate single molecule of DNA and generate reads sequentially. In this paper we demonstrate that, thanks to the sequentiality of the nanopore process, the data generated in the first tens of minutes of a typical MinION/GridION run can be exploited to resolve the alterations of a human genome at a karyotype level with a resolution in the order of tens of Mb, while the data produced in the first 6-12 hours allow to obtain a resolution comparable to currently available array-based technologies, and thanks to a novel probabilistic approach are capable to predict the allelic fraction of genomic alteration with high accuracy. To exploit the unique characteristics of nanopore sequencing data we developed a novel software tool, Nano-GLADIATOR, that is capable to perform CNVs/CNAs detection and allelic fraction prediction during the sequencing run ("On-line" mode) and after experiment completion ("Off-line" mode), revolutionizing molecular karyotyping. We tested Nano-GLADIATOR on publicly available (in "Off-line" mode) and on novel WGS dataset generated with MinION device (in "On-line" mode) showing that our tool is capable to perform real-time CNAs detection outperforming other state of the art tools. Nano-GLADIATOR is freely available at https://sourceforge.net/projects/nanogladiator/. Less...