title: Identification of medium-sized copy number alterations in whole-genome sequencing.
abstract: The genome-wide discoveries such as detection of copy number alterations (CNA) from high-throughput whole-genome sequencing data enabled new developments in personalized medicine. The CNAs have been reported to be associated with various diseases and cancers including acute myeloid leukemia. However, there are multiple challenges to the use of current CNA detection tools that lead to high false-positive rates and thus impede widespread use of such tools in cancer research. In this paper, we discuss these issues and propose possible solutions. First, since the entire genome cannot be mapped due to some regions lacking sequence uniqueness, current methods cannot be appropriately adjusted to handle these regions in the analyses. Thus, detection of medium-sized CNAs is also being directly affected by these mappability problems. The requirement for matching control samples is also an important limitation because acquiring matching controls might not be possible or might not be cost efficient. Here we present an approach that addresses these issues and detects medium-sized CNAs in cancer genomes by (1) masking unmappable regions during the initial CNA detection phase, (2) using pool of a few normal samples as control, and (3) employing median filtering to adjust CNA ratios to its surrounding coverage and eliminate false positives.
authors: Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
authors: Hatice Gulcin
authors: HG
authors: Ozer
authors: Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
authors: Aisulu
authors: A
authors: Usubalieva
authors: Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH, USA.
authors: Adrienne
authors: A
authors: Dorrance
authors: Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
authors: Ayse Selen
authors: AS
authors: Yilmaz
authors: Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH, USA.
authors: Michael
authors: M
authors: Caligiuri
authors: Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH, USA.
authors: Guido
authors: G
authors: Marcucci
authors: Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
authors: Kun
authors: K
authors: Huang
keywords: acute myeloid leukemia (AML); copy number alteration (CNA); whole-genome sequencing