Probalign: multiple sequence alignment using partition function posterior probabilities

Roshan, Usman; Livesay, Dennis R.

doi:10.1093/bioinformatics/btl472

Cited by 207 publications

(175 citation statements)

References 21 publications

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“…Alignments for each of the one-to-one rooted core genes (593 orthologs) were generated with one outgroup sequence in the alignment, which, whenever possible, was Arcrobacter. The sequences were first aligned at the amino acid level using Probalign (v1.1) (Roshan and Livesay 2006), then backtranslated to DNA, and alignment columns with a posterior probability <0.6 were removed. Alignments with >50% of the sites removed were discarded from the analysis, resulting in 571 alignments.…”

Section: Methodsmentioning

confidence: 99%

Pervasive, genome-wide positive selection leading to functional divergence in the bacterial genus Campylobacter

Lefébure

Stanhope²

2009

Genome Res.

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An open question in bacterial genomics is the role that adaptive evolution of the core genome plays in diversification and adaptation of bacterial species, and how this might differ between groups of bacteria occupying different environmental circumstances. The genus Campylobacter encompasses several important human and animal enteric pathogens, with genome sequence data available for eight species. We estimate the Campylobacter core genome at 647 genes, with 92.5% of the nonrecombinant core genome loci under positive selection in at least one lineage and the same gene frequently under positive selection in multiple lineages. Tests are provided that reject recombination, saturation, and variation in codon usage bias as factors contributing to this high level of selection. We suggest this genome-wide adaptive evolution may result from a Red Queen macroevolutionary dynamic, in which species are involved in competition for resources within the mammalian and/or vertebrate gastrointestinal tract. Much reduced levels of positive selection evident in Streptococcus, as reported by the authors in an earlier work, may be a consequence of these taxa inhabiting less species-rich habitats, and more unique niches. Despite many common loci under positive selection in multiple Campylobacter lineages, we found no evidence for molecular adaptive convergence at the level of the same or adjacent codons, or even protein domains. Taken collectively, these results describe the diversification of a bacterial genus that involves pervasive natural selection pressure across virtually the entire genome, with this adaptation occurring in different ways in different lineages, despite the species tendency toward a common gastrointestinal habitat.

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Section: Methodsmentioning

confidence: 99%

Pervasive, genome-wide positive selection leading to functional divergence in the bacterial genus Campylobacter

Lefébure

Stanhope²

2009

Genome Res.

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“…Computing match probabilities via a statistical mechanics model has been introduced for sequence-based pairwise alignment by Probalign (Roshan and Livesay 2006). However, the analogous approach has not been considered for structure-based multiple alignment.…”

Section: Match Probabilitiesmentioning

confidence: 99%

LocARNA-P: Accurate boundary prediction and improved detection of structural RNAs

Will¹,

Joshi²,

Hofacker³

et al. 2012

RNA

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Current genomic screens for noncoding RNAs (ncRNAs) predict a large number of genomic regions containing potential structural ncRNAs. The analysis of these data requires highly accurate prediction of ncRNA boundaries and discrimination of promising candidate ncRNAs from weak predictions. Existing methods struggle with these goals because they rely on sequencebased multiple sequence alignments, which regularly misalign RNA structure and therefore do not support identification of structural similarities. To overcome this limitation, we compute columnwise and global reliabilities of alignments based on sequence and structure similarity; we refer to these structure-based alignment reliabilities as STARs. The columnwise STARs of alignments, or STAR profiles, provide a versatile tool for the manual and automatic analysis of ncRNAs. In particular, we improve the boundary prediction of the widely used ncRNA gene finder RNAz by a factor of 3 from a median deviation of 47 to 13 nt. Post-processing RNAz predictions, LocARNA-P's STAR score allows much stronger discrimination between true-and false-positive predictions than RNAz's own evaluation. The improved accuracy, in this scenario increased from AUC 0.71 to AUC 0.87, significantly reduces the cost of successive analysis steps. The ready-to-use software tool LocARNA-P produces structure-based multiple RNA alignments with associated columnwise STARs and predicts ncRNA boundaries. We provide additional results, a web server for LocARNA/LocARNA-P, and the software package, including documentation and a pipeline for refining screens for structural ncRNA, at http://www.bioinf.uni-freiburg.de/Supplements/LocARNA-P/.

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“…This suggests that, rather than using a standard maximum-likelihood approach such as the Viterbi algorithm, posteriors could be profitably used to identify good alignments. Posterior decoding-alignment algorithms were proposed some time ago (Krogh 1997;Durbin et al 1998;Holmes and Durbin 1998), and recently there has been a renewed interest in probabilistic alignment algorithms, mostly focusing on proteins (Do et al 2005;Kall et al 2005;Roshan and Livesay 2006;Paten and Birney 2007), and similar approaches were found to improve RNA folding (Ding et al 2005). In contrast, the performance of posterior decoding algorithms on genomic DNA sequences has, to our knowledge, not been investigated in detail before.…”

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confidence: 99%

Uncertainty in homology inferences: Assessing and improving genomic sequence alignment

Lunter¹,

Rocco²,

Mimouni³

et al. 2007

Genome Res.

142

176

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Sequence alignment underpins all of comparative genomics, yet it remains an incompletely solved problem. In particular, the statistical uncertainty within inferred alignments is often disregarded, while parametric or phylogenetic inferences are considered meaningless without confidence estimates. Here, we report on a theoretical and simulation study of pairwise alignments of genomic DNA at human-mouse divergence. We find that >15% of aligned bases are incorrect in existing whole-genome alignments, and we identify three types of alignment error, each leading to systematic biases in all algorithms considered. Careful modeling of the evolutionary process improves alignment quality; however, these improvements are modest compared with the remaining alignment errors, even with exact knowledge of the evolutionary model, emphasizing the need for statistical approaches to account for uncertainty. We develop a new algorithm, Marginalized Posterior Decoding (MPD), which explicitly accounts for uncertainties, is less biased and more accurate than other algorithms we consider, and reduces the proportion of misaligned bases by a third compared with the best existing algorithm. To our knowledge, this is the first nonheuristic algorithm for DNA sequence alignment to show robust improvements over the classic Needleman-Wunsch algorithm. Despite this, considerable uncertainty remains even in the improved alignments. We conclude that a probabilistic treatment is essential, both to improve alignment quality and to quantify the remaining uncertainty. This is becoming increasingly relevant with the growing appreciation of the importance of noncoding DNA, whose study relies heavily on alignments. Alignment errors are inevitable, and should be considered when drawing conclusions from alignments. Software and alignments to assist researchers in doing this are provided at

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Probalign: multiple sequence alignment using partition function posterior probabilities

Abstract: Open source code implementing Probalign as well as for producing the simulated data, and all real and simulated data are freely available from http://www.cs.njit.edu/usman/probalign

Cited by 207 publications

References 21 publications

Pervasive, genome-wide positive selection leading to functional divergence in the bacterial genus Campylobacter

Pervasive, genome-wide positive selection leading to functional divergence in the bacterial genus Campylobacter

LocARNA-P: Accurate boundary prediction and improved detection of structural RNAs

Uncertainty in homology inferences: Assessing and improving genomic sequence alignment

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