A maximum-likelihood base caller for DNA sequencing

The procedures used to sequence the human genome involve the electrophoreti c separation of mixtures of dioxyribonucleic acid (DNA) fragments tagged wi th reporting groups, usually fluorescent dyes, Each fluorescent pulse which arrives from an optical detector corresponds to a nucleotide (base) in the DNA sequence, and the subsequent process of base detection is known as bas e railing. Generating longer and more accurate sequences in the base-callin g process will reduce the high cost of DNA sequencing. This paper presents ail automated base-calling algorithm, referred to as maximum-likelihood bas e caller (MLB), which is based on maximum likelihood equalization for digit al communication channels. Based on 125 experimental datasets, MLB averaged up to 40% fewer errors than the widely used ABI base caller from the Appli ed Biosystems Division of PE Corporation. MLB's accuracy rivaled that of an other well-known base caller, Phred, surpassing it on datasets with high ba ckground noise.