GOHTAM: a website for ‘Genomic Origin of Horizontal Transfers, Alignment and Metagenomics’

Copyedited by: TRJ MANUSCRIPT CATEGORY: APPLICATIONS NOTE BIOINFORMATICS APPLICATIONS NOTE Genome analysis Vol. 28 no. 9 2012, pages 1270–1271 doi:10.1093/bioinformatics/bts118 Advance Access publication March 15, 2012 GOHTAM: a website for ‘Genomic Origin of Horizontal Transfers, Alignment and Metagenomics’ Sabine Ménigaud† , Ludovic Mallet∗† , Géraldine Picord, Cécile Churlaud, Alexandre Borrel and Patrick Deschavanne∗ Molécules Thérapeutiques in silico, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-S 973, Université Paris Diderot, Sorbonne Paris Cité, 35 rue Héléne Brion, 75013, Paris, France Associate Editor: Martin Bishop Received on August 16, 2011; revised on March 2, 2012; accepted on March 6, 2012 1 INTRODUCTION Horizontal transfers (HTs) are a major force of evolution (Keeling and Palmer, 2008; Ochman et al., 2000) and this website proposes methods for their detection. The genomic signature was demonstrated to be species-specific (Deschavanne et al., 1999; Sandberg et al., 2001) and allows HT detection in terms of tetranucleotide frequencies (Dufraigne et al., 2005). Parametric methods were designed to work only with the information contained in genomic sequences. They rely either on the whole set of genes or on local variations of genomic signature (Dufraigne et al., 2005; Mallet et al., 2010). Recently, a benchmark has determined the most efficient parametric methods in different conditions and has proposed to use a combination of methods to analyze HTs in genomes (Becq et al., 2010). This site provides user-friendly access to such methods as well as some unique features including signaturebased phylogeny and potential origin of a set of metagenomics sequences. Fig. 1. Some partial screens of the website. (A) Window-based HT detection; (B) table of neighbors; (C) signature-based phylogenetic tree; (D) species signature; and (E) genome alignment. 2 2.1 whom correspondence should be addressed. authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors. † The HT detection The two methods proposed can be used alone or in combination. The first is a window-based signature method as described in Dufraigne et al. (2005), except that the distance used is the Jensen–Shannon divergence, a symmetric version of the Kullback–Leibler divergence (Azad and Lawrence, 2007; Becq et al., 2010). Either sensitivity or specificity can be increased by adjustable classification process (Azad and Lawrence, 2007). A gene-based method is also proposed with the same distance (Becq et al., 2010). Up to now, these methods were never proposed for online genome analysis (Fig. 1A). 2.2 Bank of genomic signatures A key feature of GOHTAM is the biggest bank of genomic signatures to date. Instead of using only complete genomes (van Passel et al., 2005; Teeling et al., 2004), this bank is based on the whole set of sequences of Genbank (release 188, only sequences <1 kb were discarded) and contains ∼248 000 tetranucleotide species signatures. The bank is updated at each major release. 2.3 ∗ To GOHTAM SERVICES ABSTRACT Motivation: This website allows the detection of horizontal transfers based on a combination of parametric methods and proposes an origin by researching neighbors in a bank of genomic signatures. This bank is also used to research an origin to DNA fragments from metagenomics studies. Results: Different services are provided like the possibility of inferring a phylogenetic tree with sequence signatures or comparing two genomes and displaying the rearrangements that happened since their separation. Availability and implementation: http://gohtam.rpbs.univ-parisdiderot.fr/ Contact: ; ludovic.mallet @jouy.inra.fr Supplementary information: Supplementary data are available at Bioinformatics online http://gohtam.rpbs.univ-paris-diderot.fr:8080/ Data/bin/GOHTAM_bin.tgz Origin of transferred regions Each detected region signature is compared with the signatures of the bank and the 10 closest neighbors are displayed with a confidence rating depending on the length of both query and reference sequences and the distance between the two signatures (Fig. 1B). © The Author(s) 2012. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. [15:35 10/4/2012 Bioinformatics-bts118.tex] Page: 1270 1270–1271 Copyedited by: TRJ MANUSCRIPT CATEGORY: APPLICATIONS NOTE GOHTAM 2.4 Metagenomics In the case of a metagenomics study, a sequence or a set of sequences (multi-Fasta) is loaded; the signatures of these sequences are compared as above to propose a species of origin. 2.5 Oligonucleotide content The whole set of tetranucleotides of a sequence represents the signature of a sequence (Deschavanne et al., 1999). This signature of the 256 possible tetranucleotides is under the form of a 16×16 frequency matrix and can be displayed as a signature image (Fig. 1D). 2.6 Phylogenetic tree of sequence signatures 2.7 Genome alignment The website uses maximum unique matches (MUMs) to align genomes. All rearrangements superiors to 1 kb between two genomes are graphically displayed with the possibility to choose a region or modify the length of MUMs (Fig. 1E; Delcher et al. 1999). 3 IMPLEMENTATION Except for use of programs like the Phylip package (http://evolution .gs.washington.edu/phylip.html) or Mummer (http://mummer .sourceforge.net/), the original programs are written in Python, Perl or R and available at: http://gohtam.rpbs.univ-paris-diderot.fr:8080/ Data/bin/GOHTAM_bin.tgz An online help is available. Some analyses require time; HT detection lasts ∼6 min and the research for neighbors ∼2 min depending on the server load and the sequence length. This site provides some unique features in terms of HT detection, origin of HT regions, metagenomics studies as well as for Funding: This work was supported by a grant from ANR MIE/TBHits 2010. Conflict of Interest: none declared. REFERENCES Azad,R.K. and LawrenceJ.G. (2007) Detecting laterally transferred genes: use of entropic clustering methods and genome position. Nucleic Acids Res., 35, 4629–4639. Becq,J. et al. (2010) ‘A benchmark of parametric methods for horizontal transfers detection’. PLoS ONE, 5, e9989. Chapus,C. et al. (2005) ‘Exploration of phylogenetic data using a global sequence analysis method’ BMC Evol. Biol., 5, 63–83. Delcher,A.L. et al. (1999) ‘Alignment of whole genomes’ Nucleic Acids Res, 27, 2369–2376. Deschavanne,P.J. et al. (1999). ‘Genomic signature: characterization and classification of species assessed by Chaos Game Representation of sequences’. Mol. Biol. Evol., 16, 1391–1399. Dufraigne,C. et al. (2005) ‘Detection and character (...truncated)