ENVE: a novel computational framework characterizes copy-number mutational landscapes in colorectal cancers from African American patients.
Reliable detection of somatic copy-number alterations (sCNAs) in tumors using whole-exome sequencing (WES) remains challenging owing to technical (inherent noise) and sample-associated variability in WES data. We present a novel computational framework, ENVE, which models inherent noise in any WES dataset, enabling robust detection of sCNAs across WES platforms. ENVE achieved high concordance with orthogonal sCNA assessments across two colorectal cancer (CRC) WES datasets, and consistently outperformed a best-in-class algorithm, Control-FREEC. We subsequently used ENVE to characterize global sCNA landscapes in African American CRCs, identifying genomic aberrations potentially associated with CRC pathogenesis in this population. ENVE is downloadable at https://github.com/ENVE-Tools/ENVE.
Division of General Medical Sciences-Oncology, Case Western Reserve University, Cleveland, OH 44106 USA ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 USA ; Case Western Reserve University, 2103 Cornell Road, Wolstein Research Building, Cleveland, OH 44106 USA.
Vinay
V
Varadan
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 USA.
Salendra
S
Singh
Division of Hematology and Oncology, Case Western Reserve University, Cleveland, OH 44106 USA.
Arman
A
Nosrati
Division of Hematology and Oncology, Case Western Reserve University, Cleveland, OH 44106 USA.
Lakshmeswari
L
Ravi
Division of Hematology and Oncology, Case Western Reserve University, Cleveland, OH 44106 USA.
James
J
Lutterbaugh
Division of General Medical Sciences-Oncology, Case Western Reserve University, Cleveland, OH 44106 USA ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 USA.
Jill S
JS
Barnholtz-Sloan
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 USA ; Division of Hematology and Oncology, Case Western Reserve University, Cleveland, OH 44106 USA ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106 USA ; Case Medical Center, Case Western Reserve University, Cleveland, OH 44106 USA.
Sanford D
SD
Markowitz
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 USA ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106 USA ; Case Medical Center, Case Western Reserve University, Cleveland, OH 44106 USA ; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106 USA.
Joseph E
JE
Willis
Division of General Medical Sciences-Oncology, Case Western Reserve University, Cleveland, OH 44106 USA ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 USA ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106 USA ; Case Western Reserve University, 2103 Cornell Road, Wolstein Research Building, Cleveland, OH 44106 USA.
Kishore
K
Guda
D001741:Black or African American / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D056915:DNA Copy Number Variations; D059472:Exome; D023281:Genomics; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012984:Software