2-AIN-506, 2-AIN-252: Seminar in Bioinformatics (2), (4)
Leto 2023
Abstrakt

Timour Baslan, Sam Kovaka, Fritz J. Sedlazeck, Yanming Zhang, Robert Wappel, Sha Tian, Scott W. Lowe, Sara Goodwin, Michael C. Schatz. High resolution copy number inference in cancer using short-molecule nanopore sequencing. Nucleic acids research, 49(21):e124. 2021.

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Abstract:

Genome copy number is an important source of genetic variation in health and 
disease. In cancer, Copy Number Alterations (CNAs) can be inferred from 
short-read sequencing data, enabling genomics-based precision oncology. Emerging 
Nanopore sequencing technologies offer the potential for broader clinical 
utility, for example in smaller hospitals, due to lower instrument cost, higher 
portability, and ease of use. Nonetheless, Nanopore sequencing devices are 
limited in the number of retrievable sequencing reads/molecules compared to 
short-read sequencing platforms, limiting CNA inference accuracy. To address this 
limitation, we targeted the sequencing of short-length DNA molecules loaded at 
optimized concentration in an effort to increase sequence read/molecule yield 
from a single nanopore run. We show that short-molecule nanopore sequencing 
reproducibly returns high read counts and allows high quality CNA inference. We 
demonstrate the clinical relevance of this approach by accurately inferring CNAs 
in acute myeloid leukemia samples. The data shows that, compared to traditional 
approaches such as chromosome analysis/cytogenetics, short molecule nanopore 
sequencing returns more sensitive, accurate copy number information in a cost 
effective and expeditious manner, including for multiplex samples. Our results 
provide a framework for short-molecule nanopore sequencing with applications in 
research and medicine, which includes but is not limited to, CNAs.