title: Pacific biosciences sequencing technology for genotyping and variation discovery in human data.
abstract: BACKGROUND
  Pacific Biosciences technology provides a fundamentally new data type that provides the potential to overcome some limitations of current next generation sequencing platforms by providing significantly longer reads, single molecule sequencing, low composition bias and an error profile that is orthogonal to other platforms. With these potential advantages in mind, we here evaluate the utility of the Pacific Biosciences RS platform for human medical amplicon resequencing projects.
  
  
  RESULTS
  We evaluated the Pacific Biosciences technology for SNP discovery in medical resequencing projects using the Genome Analysis Toolkit, observing high sensitivity and specificity for calling differences in amplicons containing known true or false SNPs. We assessed data quality: most errors were indels (~14%) with few apparent miscalls (~1%). In this work, we define a custom data processing pipeline for Pacific Biosciences data for human data analysis.
  
  
  CONCLUSIONS
  Critically, the error properties were largely free of the context-specific effects that affect other sequencing technologies. These data show excellent utility for follow-up validation and extension studies in human data and medical genetics projects, but can be extended to other organisms with a reference genome.
authors.affiliation: Broad Institute of MIT and Harvard, Medical and Population Genetics Program, Cambridge, MA 02141, USA. carneiro@broadinstitute.org
authors.forename: Mauricio O
authors.initials: MO
authors.lastname: Carneiro
authors.forename: Carsten
authors.initials: C
authors.lastname: Russ
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ross
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
authors.forename: Chad
authors.initials: C
authors.lastname: Nusbaum
authors.forename: Mark A
authors.initials: MA
authors.lastname: DePristo
mesh_terms: D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012984:Software; D014584:User-Computer Interface