RT Journal
A1 Ajay, Subramanian S.
A1 Parker, Stephen C.J.
A1 Ozel Abaan, Hatice
A1 Fuentes Fajardo, Karin V.
A1 Margulies, Elliott H.
T1 Accurate and comprehensive sequencing of personal genomes
JF Genome Research 
JO Genome Research 
YR 2011 
FD September 01 
VO 21 
IS 9 
SP 1498 
OP 1505 
DO 10.1101/gr.123638.111 
UL http://genome.cshlp.org/content/21/9/1498.abstract 
AB As whole-genome sequencing becomes commoditized and we begin to sequence and analyze personal genomes for clinical and diagnostic purposes, it is necessary to understand what constitutes a complete sequencing experiment for determining genotypes and detecting single-nucleotide variants. Here, we show that the current recommendation of ∼30× coverage is not adequate to produce genotype calls across a large fraction of the genome with acceptably low error rates. Our results are based on analyses of a clinical sample sequenced on two related Illumina platforms, GAIIx and HiSeq 2000, to a very high depth (126×). We used these data to establish genotype-calling filters that dramatically increase accuracy. We also empirically determined how the callable portion of the genome varies as a function of the amount of sequence data used. These results help provide a “sequencing guide” for future whole-genome sequencing decisions and metrics by which coverage statistics should be reported.