TY  - JOUR
A1  - Brockman, William
A1  - Alvarez, Pablo
A1  - Young, Sarah
A1  - Garber, Manuel
A1  - Giannoukos, Georgia
A1  - Lee, William L
A1  - Russ, Carsten
A1  - Lander, Eric S
A1  - Nusbaum, Chad
A1  - Jaffe, David B
T1  - Quality scores and SNP detection in sequencing-by-synthesis systems
Y1  - 2008/01/01 
JF  - Genome Research 
JO  - Genome Research 
DO  - 10.1101/gr.070227.107 
SP  - gr.070227.107 
UR  - http://genome.cshlp.org/content/early/2008/01/22/gr.070227.107.abstract 
N2  - Promising new sequencing technologies, based on sequencing by synthesis (SBS), are starting to deliver large amounts of DNA sequence at very low cost. Polymorphism detection is a key application. We describe general methods for improved quality scores and accurate automated polymorphism detection, and apply them to data from the Roche (454) Genome Sequencer 20.  We assess our methods using known-truth data sets, which is critical to the validity of the assessments.  

1. Improved quality scores.  We developed informative, base-by-base error predictors for this sequencer and used a variant of the PHRED binning algorithm to combine them into a single empirically derived quality score. These quality scores are more useful than those produced by the system software: they both better predict actual error rates and identify many more high-quality bases. 

2. Polymorphism detection.  We developed a SNP detection method,  with variants for low coverage, high coverage, and PCR amplicon applications, and evaluated it on known-truth data sets.  We demonstrate good specificity in single reads, and excellent specificity (no false positives in 215 kb of genome) in high-coverage data. 
ER  -