Frameshift alignment: statistics and post-genomic applications

Sheetlin, Sergey L.; Park, Yonil; Frith, Martin C.; Spouge, John L.

doi:10.1093/bioinformatics/btu576

Cited by 37 publications

(42 citation statements)

References 43 publications

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“…Classic frameshift alignment analysis aids in the identification of frameshifts in DNA sequences. 25 As AnABlast profiles identify coding sequences in the different reading frames, coding frameshifts can be also easily inferred from this computational analysis (see Cdc2 exons in Fig. 3 A).…”

Section: Resultsmentioning

confidence: 99%

AnABlast: a newin silicostrategy for the genome-wide search of novel genes and fossil regions

Jiménez

Duncan

Gallardo

et al. 2015

DNA Res

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Genome annotation, assisted by computer programs, is one of the great advances in modern biology. Nevertheless, the in silico identification of small and complex coding sequences is still challenging. We observed that amino acid sequences inferred from coding—but rarely from non-coding—DNA sequences accumulated alignments in low-stringency BLAST searches, suggesting that this alignments accumulation could be used to highlight coding regions in sequenced DNA. To investigate this possibility, we developed a computer program (AnABlast) that generates profiles of accumulated alignments in query amino acid sequences using a low-stringency BLAST strategy. To validate this approach, all six-frame translations of DNA sequences between every two annotated exons of the fission yeast genome were analysed with AnABlast. AnABlast-generated profiles identified three new copies of known genes, and four new genes supported by experimental evidence. New pseudogenes, ancestral carboxyl- and amino-terminal subtractions, complex gene rearrangements, and ancient fragments of mitDNA and of bacterial origin, were also inferred. Thus, this novel in silico approach provides a powerful tool to uncover new genes, as well as fossil-coding sequences, thus providing insight into the evolutionary history of annotated genomes.

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Section: Resultsmentioning

confidence: 99%

AnABlast: a newin silicostrategy for the genome-wide search of novel genes and fossil regions

Jiménez

Duncan

Gallardo

et al. 2015

DNA Res

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“…The LAST program [ 23 , 24 ] uses a frame-shift aware algorithm to align DNA to proteins and produces long protein alignments on long reads, even in the presence of many frame-shifts. Initial indexing of the NCBI–nr database (containing over 100 million sequences) by LAST takes over one day on a server.…”

Section: Methodsmentioning

confidence: 99%

MEGAN-LR: new algorithms allow accurate binning and easy interactive exploration of metagenomic long reads and contigs

et al. 2018

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BackgroundThere are numerous computational tools for taxonomic or functional analysis of microbiome samples, optimized to run on hundreds of millions of short, high quality sequencing reads. Programs such as MEGAN allow the user to interactively navigate these large datasets. Long read sequencing technologies continue to improve and produce increasing numbers of longer reads (of varying lengths in the range of 10k-1M bps, say), but of low quality. There is an increasing interest in using long reads in microbiome sequencing, and there is a need to adapt short read tools to long read datasets.MethodsWe describe a new LCA-based algorithm for taxonomic binning, and an interval-tree based algorithm for functional binning, that are explicitly designed for long reads and assembled contigs. We provide a new interactive tool for investigating the alignment of long reads against reference sequences. For taxonomic and functional binning, we propose to use LAST to compare long reads against the NCBI-nr protein reference database so as to obtain frame-shift aware alignments, and then to process the results using our new methods.ResultsAll presented methods are implemented in the open source edition of MEGAN, and we refer to this new extension as MEGAN-LR (MEGAN long read). We evaluate the LAST+MEGAN-LR approach in a simulation study, and on a number of mock community datasets consisting of Nanopore reads, PacBio reads and assembled PacBio reads. We also illustrate the practical application on a Nanopore dataset that we sequenced from an anammox bio-rector community.ReviewersThis article was reviewed by Nicola Segata together with Moreno Zolfo, Pete James Lockhart and Serghei Mangul.ConclusionThis work extends the applicability of the widely-used metagenomic analysis software MEGAN to long reads. Our study suggests that the presented LAST+MEGAN-LR pipeline is sufficiently fast and accurate.

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“…Pseudogenes are annotated using protein-DNA alignments allowing for frame shifts ( 16 ) using the LAST aligner ( 17 ). The resulting alignments are combined into superhits using an approach similar to the one employed by PseudoPipe ( 18 ).…”

Section: Methodsmentioning

confidence: 99%

Companion: a web server for annotation and analysis of parasite genomes

et al. 2016

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Currently available sequencing technologies enable quick and economical sequencing of many new eukaryotic parasite (apicomplexan or kinetoplastid) species or strains. Compared to SNP calling approaches, de novo assembly of these genomes enables researchers to additionally determine insertion, deletion and recombination events as well as to detect complex sequence diversity, such as that seen in variable multigene families. However, there currently are no automated eukaryotic annotation pipelines offering the required range of results to facilitate such analyses. A suitable pipeline needs to perform evidence-supported gene finding as well as functional annotation and pseudogene detection up to the generation of output ready to be submitted to a public database. Moreover, no current tool includes quick yet informative comparative analyses and a first pass visualization of both annotation and analysis results. To overcome those needs we have developed the Companion web server (http://companion.sanger.ac.uk) providing parasite genome annotation as a service using a reference-based approach. We demonstrate the use and performance of Companion by annotating two Leishmania and Plasmodium genomes as typical parasite cases and evaluate the results compared to manually annotated references.

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Frameshift alignment: statistics and post-genomic applications

Cited by 37 publications

References 43 publications

AnABlast: a newin silicostrategy for the genome-wide search of novel genes and fossil regions

AnABlast: a newin silicostrategy for the genome-wide search of novel genes and fossil regions

MEGAN-LR: new algorithms allow accurate binning and easy interactive exploration of metagenomic long reads and contigs

Companion: a web server for annotation and analysis of parasite genomes

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