Abstract
BackgroundThe ability to rapidly map millions of oligonucleotide fragments to a reference genome is crucial to many high throughput genomic technologies.ResultsWe propose an intuitive and efficient algorithm, titled extreme MApping of OligoNucleotide (xMAN), to rapidly map millions of oligonucleotide fragments to a genome of any length. By converting oligonucleotides to integers hashed in RAM, xMAN can scan through genomes using bit shifting operation and achieve at least one order of magnitude speed increase over existing tools. xMAN can map the 42 million 25-mer probes on the Affymetrix whole human genome tiling arrays to the entire genome in less than 6 CPU hours.ConclusionsIn addition to the speed advantage, we found the probe mapping of xMAN to substantially improve the final analysis results in both a spike-in experiment on ENCODE tiling arrays and an estrogen receptor ChIP-chip experiment on whole human genome tiling arrays. Those improvements were confirmed by direct ChIP and real-time PCR assay. xMAN can be further extended for application to other high-throughput genomic technologies for oligonucleotide mapping.
Highlights
The ability to rapidly map millions of oligonucleotide fragments to a reference genome is crucial to many high throughput genomic technologies
We propose an intuitive and efficient method xMAN for the rapid mapping of millions of query oligonucleotide fragments to the reference genome of any given length. xMAN differs significantly from existing algorithms
We focus our study on Affymetrix tiling arrays since they have the highest probe density, with approximate 42 million 25-mer probes covering the nonrepetitive human genome at 35 bp resolution
Summary
The ability to rapidly map millions of oligonucleotide fragments to a reference genome is crucial to many high throughput genomic technologies. Since the arrays were usually designed based on an older genome assembly, it is important to remap all the probes to the newest genome assembly or transcriptome annotation during data analysis [1], under the assumption that the current genome and transcriptome are more precise than the earlier ones It is not uncommon for a probe to map to multiple locations in the genome. Estrogen receptor whole-genome ChIP-chip experiment using xMAN or Affymetrix probe mapping. We applied MAT with xMAN or Affymetrix probe mapping to the estrogen receptor ChIP-chip experiment on Affymetrix human genome 1.0 tiling array set, which consists of 14 arrays covering the non-repetitive human genome at 35 bp resolution. Under the same FDR cutoff, MAT predicts more true positive peaks using xMAN probe mapping than using Affymetrix probe mapping
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