Analysis of cfDNA fragmentomics metrics and commercial targeted sequencing panels
Abstract
Abstract Fragmentomics based analysis of cell-free DNA (cfDNA) has recently emerged as a method to infer epigenetic and transcriptional data. Many of these reports analyze whole genome sequencing (WGS) which is not readily available clinically. Targeted exon panels are used for clinical cfDNA variant calling. In this report, we conduct an investigation of multiple published fragmentomics methods for WGS, but on cancer exon panels. We find that strategies utilizing normalized depth metrics, as well as all exons present on the panel, generally allow for better prediction of cancer phenotypes across a range of tumor fractions, though other metrics work particularly well in specific applications. Additionally, genes from commercial clinical targeted sequencing panels could be similarly employed for cancer phenotyping with a minimal decrease in performance despite their smaller genomic coverage. These results suggest that fragmentomics-based analysis of cfDNA can utilize targeted sequencing panels and does not necessarily require additional WGS.
Article Details
Authors (27)
Kyle T. Helzer
Marina N. Sharifi
Jamie M. Sperger
Matthew R. Chrostek
Matthew L. Bootsma
Shannon R. Reese
Amy Taylor
Katie R. Kaufmann
Hannah Krause
Jennifer Schehr
Nan Sethakorn
David Kosoff
Christos E. Kyriakopoulos
Division of Hematology and Medical Oncology, University of Wisconsin Carbone Cancer Center
Michael Bassetti
Grace Blitzer
John Floberg
Martin Sjöström
Andrew J. Armstrong
Himisha Beltran
Rana R. McKay
Department of Medicine, Urology, and Radiation Medicine and Applied Sciences University of California‐San Diego La Jolla California USA
Felix Y. Feng
Ruth O’Regan
Kari B. Wisinski
Hamid Emamekhoo
Alex W. Wyatt
Joshua M. Lang
Department of Medicine, University of Wisconsin-Madison
Shuang G. Zhao