CSC2431 February 3rd 2010 Alecia Fowler Fast and Accurate Short Read Alignment with Burrows-Wheeler Transform Heng Li and Richard Durban CSC2431 February 3rd 2010 Alecia Fowler

Short Read Alignment SPEED AND ACCURACY

Burrows Wheeler Aligner OVERVIEW: based on backward search and Burrows-Wheeler Transform (BWT) FEATURES: performs gapped alignment for single-end reads, supports paired-end mapping, generates mapping quality PLATFORM: Illumina; SOLiD; 454; Sanger PROS: fast CONS: short read algorithm is slow for long reads and reads with high error rate

Prefix trie X = GOOGOL$ “G” “GO” “GOO” “GOOG” “GOOGO” “GOOGOL”

Burrows-Wheeler Transform (BWT) Algorithm used for data compression Output is easier to compress as it groups similar symbols together Text compression method Takes a block of data and rearranges it using a sorting algorithm String is built by sorting all of the circular shifts of a string and concatenating the last characters of each circular shift Key feature is the first-last property, in that the k-th occurrence of a character in the BWT string corresponds to its kth occurrence in the list of sorted circularshifts

Suffix array interval and sequence alignment

Exact and Inexact Matching W = LOL X = GOOGOL$ Has to account for mismatches or gaps in the reads the BWT index of the reverse reference sequence narrows the search space

Evaluation: Simulated Data Simulated reads from human genome One million pairs of different lengths Mapped to the human genome BWA was found to be more accurate than Bowtie and SOAPv2 Would need to sacrifice mapping quality in order to increase speed

Evaluation: Real Data 12.2 million pairs of 51bp reads from a male genome Mapped to human genome and a human-chicken hybrid reference Had high speed and accuracy for both