Efficient multiple genome alignment

Höhl, Michael; Kurtz, Stefan; Ohlebusch, Enno

doi:10.1093/bioinformatics/18.suppl_1.s312

Cited by 141 publications

(125 citation statements)

References 23 publications

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“…The genomic sequences were aligned with multiple genome alignment methods (38), and the alignment was screened for SNPs by using software described in ref. 39.…”

Section: Methodsmentioning

confidence: 99%

On the origin of smallpox: Correlating variola phylogenics with historical smallpox records

Liu

Carroll

Gardner

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

182

143

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Human disease likely attributable to variola virus (VARV), the etiologic agent of smallpox, has been reported in human populations for >2,000 years. VARV is unique among orthopoxviruses in that it is an exclusively human pathogen. Because VARV has a large, slowly evolving DNA genome, we were able to construct a robust phylogeny of VARV by analyzing concatenated single nucleotide polymorphisms (SNPs) from genome sequences of 47 VARV isolates with broad geographic distributions. Our results show two primary VARV clades, which likely diverged from an ancestral African rodent-borne variola-like virus either Ϸ16,000 or Ϸ68,000 years before present (YBP), depending on which historical records (East Asian or African) are used to calibrate the molecular clock. One primary clade was represented by the Asian VARV major strains, the more clinically severe form of smallpox, which spread from Asia either 400 or 1,600 YBP. Another primary clade included both alastrim minor, a phenotypically mild smallpox described from the American continents, and isolates from West Africa. This clade diverged from an ancestral VARV either 1,400 or 6,300 YBP, and then further diverged into two subclades at least 800 YBP. All of these analyses indicate that the divergence of alastrim and variola major occurred earlier than previously believed.evolution ͉ SNPs ͉ variola virus

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“…The genomic sequences were aligned with multiple genome alignment methods (38), and the alignment was screened for SNPs by using software described in ref. 39.…”

Section: Methodsmentioning

confidence: 99%

On the origin of smallpox: Correlating variola phylogenics with historical smallpox records

Liu

Carroll

Gardner

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

182

143

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“…We conducted a similarity search against human chromosomes (Ensembl, release 12.31) by using MEGABLAST to roughly map chimpanzee and baboon sequences on their orthologous loci. We then used human͞chimpanzee and human͞ baboon pairwise alignments computed by MGA (16) to generate an accurate mapping, which enabled us to identify potential triple alignments. Finally, the alignments were generated by using CLUSTALW and comprised a total of 16.0 megabases of orthologous sites distributed on 17 human chromosomes.…”

Section: Methodsmentioning

confidence: 99%

Homology-dependent methylation in primate repetitive DNA

Meunier

Khelifi

Navratil

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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In mammals, several studies have suggested that levels of methylation are higher in repetitive DNA than in nonrepetitive DNA, possibly reflecting a genome-wide defense mechanism against deleterious effects associated with transposable elements (TEs). To analyze the determinants of methylation patterns in primate repetitive DNA, we took advantage of the fact that the methylation rate in the germ line is reflected by the transition rate at CpG sites. We assessed the variability of CpG substitution rates in nonrepetitive DNA and in various TE and retropseudogene families. We show that, unlike other substitution rates, the rate of transition at CpG sites is significantly (37%) higher in repetitive DNA than in nonrepetitive DNA. Moreover, this rate of CpG transition varies according to the number of repeats, their length, and their level of divergence from the ancestral sequence (up to 2.7 times higher in long, lowly divergent TEs compared with unique sequences). This observation strongly suggests the existence of a homology-dependent methylation (HDM) mechanism in mammalian genomes. We propose that HDM is a direct consequence of interfering RNA-induced transcriptional gene silencing.RNA interference ͉ transposable element ͉ substitution rate ͉ CpG T ransposable element (TE) activity within genomes may have numerous deleterious consequences, such as their insertions into genes or regulatory elements, or genomic disorders resulting from ectopic recombination between homologous TE copies (1). Thus, specific mechanisms that limit such deleterious effects within genomes are expected to have arisen. Indeed, Selker et al.(2) discovered in Neurospora crassa a defense mechanism against TEs associated with DNA methylation [namely, RIP (Repeat Induced Point mutations)]. DNA methylation in the genome of N. crassa is exclusively confined to repeated sequences (3, 4) and causes their inactivation in no more than one generation (reviewed in ref. 3). Although this mechanism is not entirely understood, DNA methylation is triggered by the existence of two or more homologous DNA sequences longer than a few hundred base pairs (3). The immediate inactivation of methylated sequences in N. crassa is a result of massive C-to-T mutational events due to the deamination of methylated cytosines into thymines, which is likely to be induced by the methylase itself (5, 6). Another example indicating that DNA methylation controls the potential deleterious effects of TEs comes from plants: Only TEs exhibit high methylation levels, which prevents their expression (7,8). In mammals, several lines of experimental and theoretical evidence suggest the existence of a specific methylation pattern in TEs (9-14). For instance, TEs in Mus musculus retain their methylated state during early embryonic stages, whereas nonrepetitive DNA becomes nonmethylated (14). In the same species, Yates et al. (12) demonstrated that tandem B1 elements can induce strong de novo DNA methylation. In humans, Chesnokov and Schmid (11) discovered that Alu elements in the germ lin...

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“…The second approach consists in retrieving the maximal exact matches (MEMs), which are WMs that cannot be extended either from their left nor from their right. MEMs are widely used as anchor points in complete genome alignment (Höhl et al, 2002) as well as in alignment-free methods (Deloger et al, 2009). It is noteworthy that, in comparative genomics, most of the studies that use WMs are based on the detection of MEMs rather than k-words.…”

Section: Introduction Fmentioning

confidence: 99%

Separating Significant Matches from Spurious Matches in DNA Sequences

Devillers

Schbath

2012

Journal of Computational Biology

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Word matches are widely used to compare genomic sequences. Complete genome alignment methods often rely on the use of matches as anchors for building their alignments, and various alignment-free approaches that characterize similarities between large sequences are based on word matches. Among matches that are retrieved from the comparison of two genomic sequences, a part of them may correspond to spurious matches (SMs), which are matches obtained by chance rather than by homologous relationships. The number of SMs depends on the minimal match length (') that has to be set in the algorithm used to retrieve them. Indeed, if ' is too small, a lot of matches are recovered but most of them are SMs. Conversely, if ' is too large, fewer matches are retrieved but many smaller significant matches are certainly ignored. To date, the choice of ' mostly depends on empirical threshold values rather than robust statistical methods. To overcome this problem, we propose a statistical approach based on the use of a mixture model of geometric distributions to characterize the distribution of the length of matches obtained from the comparison of two genomic sequences.

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Efficient multiple genome alignment

Cited by 141 publications

References 23 publications

On the origin of smallpox: Correlating variola phylogenics with historical smallpox records

On the origin of smallpox: Correlating variola phylogenics with historical smallpox records

Homology-dependent methylation in primate repetitive DNA

Separating Significant Matches from Spurious Matches in DNA Sequences

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