Batch Effects in Tumor-Only Next-Generation Sequencing Panel Sequencing and Implications for Copy Number Variant Detection

Next-generation sequencing is routinely performed in clinical practice to detect various types of mutations for targeted therapy, diagnosis, and prognosis. Actionable alterations detected by next-generation sequencing include not only nonsynonymous mutations that lead to functional or structural changes of proteins but also copy number variants (CNVs) that affect gene dosage, such as gene copy gains, amplifications, or deletions. Among tumor-only CNV detection methods, the use of a panel of normals for relative comparison has become a common practice, largely because of the lack of matched normal samples.