PALMA: mRNA to genome alignments using large margin algorithms.
BACKGROUND
Despite many years of research on how to properly align sequences in the presence of sequencing errors, alternative splicing and micro-exons, the correct alignment of mRNA sequences to genomic DNA is still a challenging task.


RESULTS
We present a novel approach based on large margin learning that combines accurate splice site predictions with common sequence alignment techniques. By solving a convex optimization problem, our algorithm-called PALMA-tunes the parameters of the model such that true alignments score higher than other alignments. We study the accuracy of alignments of mRNAs containing artificially generated micro-exons to genomic DNA. In a carefully designed experiment, we show that our algorithm accurately identifies the intron boundaries as well as boundaries of the optimal local alignment. It outperforms all other methods: for 5702 artificially shortened EST sequences from Caenorhabditis elegans and human, it correctly identifies the intron boundaries in all except two cases. The best other method is a recently proposed method called exalin which misaligns 37 of the sequences. Our method also demonstrates robustness to mutations, insertions and deletions, retaining accuracy even at high noise levels.


BACKGROUND
Datasets for training, evaluation and testing, additional results and a stand-alone alignment tool implemented in C++ and python are available at http://www.fml.mpg.de/raetsch/projects/palma
Schulze
Uta
U
Friedrich Miescher Laboratory, Max Planck Society, Tübingen, Germany.
Hepp
Bettina
B
Ong
Cheng Soon
CS
Rätsch
Gunnar
G
D000465:Algorithms; D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D017124:Conserved Sequence / Q000235:genetics*; D020224:Expressed Sequence Tags; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid; D012984:Software
D012333:RNA, Messenger