Human genome sequencing on PromethION: Characterization of structural variants and repetitive regions

Thu, Oct 11, 2018 3:59 PM BST{LOCAL_TZ}

Human genome sequencing on PromethION: Characterization of structural variants and repetitive regions

Thu, Oct 11, 2018 3:59 PM BST


Abstract:

At the VIB-UAntwerp Center for Molecular Neurology, we apply sequencing technologies to elucidate the genetic etiology of neurodegenerative brain diseases such as Alzheimer Disease and Frontotemporal Dementia. Structural variation and repetitive regions are insufficiently characterized using currently dominant short-read sequencing technologies. Long-read sequencing on the Oxford Nanopore PromethION has the potential for a comprehensive identification of larger genomic variation, including expansions of STR and VNTR sequences.

We sequenced a dozen human genomes on the PromethION platform, including an extreme depth coverage reference genome from the Yoruban individual NA19240. On average, we obtained 68 Gbase (~ 21.2x genome coverage) output per PromethION flow cell, with a maximum of 98.0 Gbase (30.6x).

We evaluated the available basecalling, alignment, and variant calling tools to detect structural variants and tandem repeat lengths, and compared the results to existing datasets. Based on our findings we present an efficient workflow for structural variant identification and annotation from long-read sequencing. In addition, we designed a novel algorithm to resolve (expanded) tandem repeats on raw squiggle data enabling higher accuracy, detection of sequence composition, and potential analysis of nucleotide modifications.

In conclusion, we will demonstrate the feasibility of long-read sequencing on PromethION to characterize structural variation and repetitive sequences in the human genome with an unprecedented resolution.

Speakers:


Arne De Roeck - Center for Molecular Neurology, VIB, University of Antwerp

Arne De Roeck is a PhD student in the Neurodegenerative Brain Diseases Group at the Center for Molecular Neurology (CMN), VIB – University of Antwerp. He studies the complex genetics of Alzheimer’s disease (AD). He identified a novel VNTR affecting AD and is designing an algorithm to accurately determine length, sequence, and nucleotide modifications in this tandem repeat using whole genome PromethION sequencing.








Wouter De Coster - Center for Molecular Neurology, VIB, University of Antwerp
Wouter De Coster is a bioinformatics PhD student in the lab of Christine Van Broeckhoven at the Antwerp VIB Center of Molecular Neurology. In his research, he investigates the genetic etiology of neurodegenerative diseases such as Alzheimer Disease and Frontotemporal Dementia using long read sequencing on the Oxford Nanopore MinION and PromethION platforms. He has developed NanoPack, a package of software tools for quality assessment and processing of long read sequencing data.  As an early adopter of new technologies, Wouter is exploring the possibilities of whole-genome sequencing on the PromethION, with the main objective of identifying structural variants underlying neurodegeneration.






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