title: Current Methods for Automated Filtering of Multiple Sequence Alignments Frequently Worsen Single-Gene Phylogenetic Inference.
abstract: Phylogenetic inference is generally performed on the basis of multiple sequence alignments (MSA). Because errors in an alignment can lead to errors in tree estimation, there is a strong interest in identifying and removing unreliable parts of the alignment. In recent years several automated filtering approaches have been proposed, but despite their popularity, a systematic and comprehensive comparison of different alignment filtering methods on real data has been lacking. Here, we extend and apply recently introduced phylogenetic tests of alignment accuracy on a large number of gene families and contrast the performance of unfiltered versus filtered alignments in the context of single-gene phylogeny reconstruction. Based on multiple genome-wide empirical and simulated data sets, we show that the trees obtained from filtered MSAs are on average worse than those obtained from unfiltered MSAs. Furthermore, alignment filtering often leads to an increase in the proportion of well-supported branches that are actually wrong. We confirm that our findings hold for a wide range of parameters and methods. Although our results suggest that light filtering (up to 20% of alignment positions) has little impact on tree accuracy and may save some computation time, contrary to widespread practice, we do not generally recommend the use of current alignment filtering methods for phylogenetic inference. By providing a way to rigorously and systematically measure the impact of filtering on alignments, the methodology set forth here will guide the development of better filtering algorithms.
authors.affiliation: Department of Computer Science, ETH Zurich, Universitätstr. 6, 8092 Zurich, Switzerland, Department of Molecular Sciences, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK; MRC Clinical Sciences Centre, London W12 0NN, UK;
authors.forename: Ge
authors.initials: G
authors.lastname: Tan
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK;
authors.forename: Matthieu
authors.initials: M
authors.lastname: Muffato
authors.affiliation: Department of Computer Science, ETH Zurich, Universitätstr. 6, 8092 Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Ledergerber
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK; University College London, Gower St, London WC1E 6BT, UK; and.
authors.forename: Javier
authors.initials: J
authors.lastname: Herrero
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK;
authors.forename: Nick
authors.initials: N
authors.lastname: Goldman
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstr. 190 , 8057 Zurich, Switzerland; and Swiss Institute of Bioinformatics, Universitätstr. 6, 8092 Zurich, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Gil
authors.affiliation: University College London, Gower St, London WC1E 6BT, UK; and European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK; c.dessimoz@ucl.ac.uk.
authors.forename: Christophe
authors.initials: C
authors.lastname: Dessimoz
mesh_terms: D000465:Algorithms; D002965:Classification / Q000379:methods*; D016678:Genome / Q000235:genetics; D010802:Phylogeny; D015203:Reproducibility of Results; D016415:Sequence Alignment
keywords: alignment filtering; alignment trimming; molecular phylogeny; multiple sequence alignment; phylogenetic inference; phylogenetics; phylogeny