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Given two genomic DNA sequences, the syntenic alignment problem is to compute an ordered list of subsequences for each sequence such that the corresponding subsequence pairs exhibit a high degree of similarity. Syntenic alignments are useful in comparing genomic DNA from related species and in identifying conserved genes. In this paper, we present a parallel algorithm for computing syntenic alignments that runs in time, where m and n are the respective lengths of the two genomic sequences, and p is the number of processors used. Our algorithm is time optimal with respect to the corresponding sequential algorithm and can use processors, where n is the length of the larger sequence. The space requirement of the algorithm is per processor. Using an implementation of this parallel algorithm, we report the alignment of a gene-rich region of human chromosome 12, namely 12p13 and its syntenic region in mouse chromosome 6 (both over 220,000 base pairs in length) in under 24 minutes on a 64-processor IBM xSeries cluster.
Optimal spaced seeds were developed as a method to increase sensitivity of local alignment programs similar to BLASTN. Such seeds have been used before in the program PatternHunter, and have given improved sensitivity and running time relative to BLASTN in genome–genome comparison. We study the problem of computing optimal spaced seeds for detecting homologous coding regions in unannotated genomic sequences. By using well-chosen seeds, we are able to improve the sensitivity of coding sequence alignment over that of TBLASTX, while keeping runtime comparable to BLASTN. We identify good seeds by first giving effective hidden Markov models of conservation in alignments of homologous coding regions. We give an efficient algorithm to compute the optimal spaced seed when conservation patterns are generated by these models. Our results offer the hope of improved gene finding due to fewer missed exons in DNA/DNA comparison, and more effective homology search in general, and may have applications outside of bioinformatics.
We have developed a generic framework for combining introns from genomicly aligned expressed–sequence–tag clusters with a set of exon predictions to produce alternative transcript predictions. Our current implementation uses ASPIC to generate alternative transcripts from EST mappings. Introns from ASPIC and a set of gene predictions from many diverse gene prediction programs are given to the gene prediction combiner GenePC which then generates alternative consensus splice forms. We evaluated our method on the ENCODE regions of the human genome. In general we see a marked improvement in transcript-level sensitivity due to the fact that more than one transcript per gene may now be predicted. GenePC, which alone is highly specific at the transcript level, balances the lower specificity of ASPIC.
RNAz is a widely used software package for de novo detection of structured noncoding RNAs in comparative genomics data. Four years of experience have not only demonstrated the applicability of the approach, but also helped us to identify limitations of the current implementation. RNAz 2.0 provides significant improvements in two respects: (1) The accuracy is increased by the systematic use of dinucleotide models. (2) Technical limitations of the previous version, such as the inability to handle alignments with more than six sequences, are overcome by increased training data and the usage of an entropy measure to represent sequence similarities. RNAz 2.0 shows a significantly lower false discovery rate on a dinucleotide background model than the previous version. Separate models for structural alignments provide an additional way to increase the predictive power. RNAz is open source software and can be obtained free of charge at: http://www.tbi.univie.ac.at/~wash/RNAz/