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Scale-invariant structure of strongly conserved sequence in genomic intersections and alignments.

ABSTRACT: A power-law distribution of the length of perfectly conserved sequence from mouse/human whole-genome intersection and alignment is exhibited. Spatial correlations of these elements within the mouse genome are studied. It is argued that these power-law distributions and correlations are comprised in part by functional noncoding sequence and ought to be accounted for in estimating the statistical significance of apparent sequence conservation. These inter-genomic correlations of conservation are placed in the context of previously observed intra-genomic correlations, and their possible origins and consequences are discussed.

SUBMITTER: Salerno W

PROVIDER: S-EPMC1559763 | biostudies-literature | 2006 Aug

REPOSITORIES: biostudies-literature

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Scale-invariant structure of strongly conserved sequence in genomic intersections and alignments.

Salerno William W Havlak Paul P Miller Jonathan J

Proceedings of the National Academy of Sciences of the United States of America 20060821 35

A power-law distribution of the length of perfectly conserved sequence from mouse/human whole-genome intersection and alignment is exhibited. Spatial correlations of these elements within the mouse genome are studied. It is argued that these power-law distributions and correlations are comprised in part by functional noncoding sequence and ought to be accounted for in estimating the statistical significance of apparent sequence conservation. These inter-genomic correlations of conservation are p ...[more]

PMID: 16924100

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Project description:BackgroundGenomic sequence data cannot be fully appreciated in isolation. Comparative genomics--the practice of comparing genomic sequences from different species--plays an increasingly important role in understanding the genotypic differences between species that result in phenotypic differences as well as in revealing patterns of evolutionary relationships. One of the major challenges in comparative genomics is producing a high-quality alignment between two or more related genomic sequences. In recent years, a number of tools have been developed for aligning large genomic sequences. Most utilize heuristic strategies to identify a series of strong sequence similarities, which are then used as anchors to align the regions between the anchor points. The resulting alignment is globally correct, but in many cases is suboptimal locally. We describe a new program, GenAlignRefine, which improves the overall quality of global multiple alignments by using a genetic algorithm to improve local regions of alignment. Regions of low quality are identified, realigned using the program T-Coffee, and then refined using a genetic algorithm. Because a better COFFEE (Consistency based Objective Function For alignmEnt Evaluation) score generally reflects greater alignment quality, the algorithm searches for an alignment that yields a better COFFEE score. To improve the intrinsic slowness of the genetic algorithm, GenAlignRefine was implemented as a parallel, cluster-based program.ResultsWe tested the GenAlignRefine algorithm by running it on a Linux cluster to refine sequences from a simulation, as well as refine a multiple alignment of 15 Orthopoxvirus genomic sequences approximately 260,000 nucleotides in length that initially had been aligned by Multi-LAGAN. It took approximately 150 minutes for a 40-processor Linux cluster to optimize some 200 fuzzy (poorly aligned) regions of the orthopoxvirus alignment. Overall sequence identity increased only slightly; but significantly, this occurred at the same time that the overall alignment length decreased--through the removal of gaps--by approximately 200 gapped regions representing roughly 1,300 gaps.ConclusionWe have implemented a genetic algorithm in parallel mode to optimize multiple genomic sequence alignments initially generated by various alignment tools. Benchmarking experiments showed that the refinement algorithm improved genomic sequence alignments within a reasonable period of time.

Dataset Information

Scale-invariant structure of strongly conserved sequence in genomic intersections and alignments.

Publications

Scale-invariant structure of strongly conserved sequence in genomic intersections and alignments.

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