Table 1.

Variant callers and laboratory protocols to address selected sequencing scenarios.

Features	Laboratory intervention	Recommended variant callers
Germline contamination	Germline control	JointSNVMix [30], Strelka2 [32], MuTect2 [10], SNVSniffer [33]
Highly admixed sample	Germline sample + normal controls	VarDict [11], Platypus [40], EBCall [34]
Archival FFPE sample		VarDict [11], Platypus [40], DeepSNVMiner [16]
Cell-free DNA		iDES [20], SiNVICT [82]
Unique molecular identifiers (UMIs)		DeepSNVMiner [16], iDES [20], MAGERI [45], smCounter2 [17,18]
Exome sequencing	Dual-indexed sequencing	MuTect2 [10], Strelka2 [32], EBCall [34]
Targeted sequencing		LoFreqStar [13], VarDict [11]
Bead-based sequencing		MuTect2 [10], VarDict [11], HapMuC [66]
Single-molecule real-time (SMRT)		GenomicConsensus [70]
Nanopore		PoreSeq [127]
Important low-frequency variants	UMI-based sequencing	DeepSNVMiner [16], smCounter2 [18], MuTect2 [10], VarDict [11], Platypus [40]
Chromosomal instability		VarDict [11], Seurat [98], Platypus [40]
Pediatric patient		MuTect2 [10], Platypus [40], SomVarIUS [129], Pisces [109]
Hereditary disease	Germline control	VarDict [11], Platypus [40], Pisces [109], VarScan2 [12], HaplotypeCaller [7]