Biology subjects

Ari Löytynoja

Publications and source records attributed to Ari Löytynoja.

3 recordsLinked to original sources

bioRxiv2016

Co-estimation of Phylogeny-aware Alignment and Phylogenetic Tree

The phylogeny-aware alignment algorithm implemented in both PRANK and PAGAN has been found to produce highly accurate alignments for comparative sequence analysis. However, the algorithms reliance on a guide tree during the alignment process can bias the resulting alignment rendering it unsuitable for phylogenetic inference. To overcome these issues, we have developed a new tool, Canopy, for parallelized iterative search of optimal alignment. Using Canopy, we studied the impact of the guide tree as well as the number and relative divergence of sequences on the accuracy of the alignment and inferred phylogeny. We find that PAGAN is the more robust of the two phylogeny-aware alignment methods to errors in the guide tree, but Canopy largely resolves the guide tree-related biases in PRANK. We demonstrate that, for all experimental settings tested, Canopy produces the most accurate sequence alignments and, further, that the inferred phylogenetic trees are of comparable accuracy to those obtained with the leading alternative method, SATe. Our analyses also show that, unlike traditional alignment algorithms, the phylogeny-aware algorithm effectively uses the information from denser sequence sampling and produces more accurate alignments when additional closely-related sequences are included. All methods are available for download at http://wasabiapp.org/software.

Bioinformatics↗

bioRxiv2016

Glutton: large-scale integration of non-model organism transcriptome data for comparative analysis

High-throughput RNA-seq data has become ubiquitous in the study of non-model organisms, but its use in comparative analysis remains a challenge. Without a reference genome for mapping, sequence data has to be de novo assembled, producing large numbers of short, highly redundant contigs. Preparing these assemblies for comparative analyses requires the removal of redundant isoforms, assignment of orthologs and converting fragmented transcripts into gene alignments. In this article we present Glutton, a novel tool to process transcriptome assemblies for downstream evolutionary analyses. Glutton takes as input a set of fragmented, possibly erroneous transcriptome assemblies. Utilising phylogeny-aware alignment and reference data from a closely related species, it reconstructs one transcript per gene, finds orthologous sequences and produces accurate multiple alignments of coding sequences. We present a comprehensive analysis of Gluttons performance across a wide range of divergence times between study and reference species. We demonstrate the impact choice of assembler has on both the number of alignments and the correctness of ortholog assignment and show substantial improvements over heuristic methods, without sacrificing correctness. Finally, using inference of Darwinian selection as an example of downstream analysis, we show that Glutton-processed RNA-seq data give results comparable to those obtained from full length gene sequences even with distantly related reference species. Glutton is available from http://wasabiapp.org/software/glutton/ and is licensed under the GPLv3.

Bioinformatics↗

bioRxiv2016

Short template switch events explain mutation clusters in the human genome

Resequencing efforts are uncovering the extent of genetic variation in humans and provide data to study the evolutionary processes shaping our genome. One recurring puzzle in both intra- and inter-species studies is the high frequency of complex mutations comprising multiple nearby base substitutions or insertion-deletions. We devised a generalized mutation model of template switching during replication that extends existing models of genome rearrangement, and used this to study the role of template switch events in the origin of such mutation clusters. Applied to the human genome, our model detects thousands of template switch events during the evolution of human and chimp from their common ancestor, and hundreds of events between two independently sequenced human genomes. While many of these are consistent with the template switch mechanism previously proposed for bacteria but not thought significant in higher organisms, our model also identifies new types of mutations that create short inversions, some flanked by paired inverted repeats. The local template switch process can create numerous complex mutation patterns, including hairpin loop structures, and explains multi-nucleotide mutations and compensatory substitutions without invoking positive selection, complicated and speculative mechanisms, or implausible coincidence. Clustered sequence differences are challenging for mapping and variant calling methods, and we show that detection of mutation clusters with current resequencing methodologies is difficult and many erroneous variant annotations exist in human reference data. Template switch events such as those we have uncovered may have been neglected as an explanation for complex mutations because of biases in commonly used analyses. Incorporation of our model into reference-based analysis pipelines and comparisons of de novo-assembled genomes will lead to improved understanding of genome variation and evolution.

Genomics↗