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Open Access Software

Unsupervised genome-wide recognition of local relationship patterns

Neda Zamani1, Pamela Russell2, Henrik Lantz1, Marc P Hoeppner1, Jennifer RS Meadows1, Nagarjun Vijay3, Evan Mauceli4, Federica di Palma2, Kerstin Lindblad-Toh12, Patric Jern1 and Manfred G Grabherr12*

Author Affiliations

1 Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

2 Broad Institute of MIT and Harvard, Cambridge, MA, USA

3 Department of Ecology and Genetics, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden

4 Boston Children’s Hospital, Boston, MA, USA

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BMC Genomics 2013, 14:347  doi:10.1186/1471-2164-14-347

Published: 24 May 2013

Abstract

Background

Phenomena such as incomplete lineage sorting, horizontal gene transfer, gene duplication and subsequent sub- and neo-functionalisation can result in distinct local phylogenetic relationships that are discordant with species phylogeny. In order to assess the possible biological roles for these subdivisions, they must first be identified and characterised, preferably on a large scale and in an automated fashion.

Results

We developed Saguaro, a combination of a Hidden Markov Model (HMM) and a Self Organising Map (SOM), to characterise local phylogenetic relationships among aligned sequences using cacti, matrices of pair-wise distance measures. While the HMM determines the genomic boundaries from aligned sequences, the SOM hypothesises new cacti in an unsupervised and iterative fashion based on the regions that were modelled least well by existing cacti. After testing the software on simulated data, we demonstrate the utility of Saguaro by testing two different data sets: (i) 181 Dengue virus strains, and (ii) 5 primate genomes. Saguaro identifies regions under lineage-specific constraint for the first set, and genomic segments that we attribute to incomplete lineage sorting in the second dataset. Intriguingly for the primate data, Saguaro also classified an additional ~3% of the genome as most incompatible with the expected species phylogeny. A substantial fraction of these regions was found to overlap genes associated with both the innate and adaptive immune systems.

Conclusions

Saguaro detects distinct cacti describing local phylogenetic relationships without requiring any a priori hypotheses. We have successfully demonstrated Saguaro’s utility with two contrasting data sets, one containing many members with short sequences (Dengue viral strains: n = 181, genome size = 10,700 nt), and the other with few members but complex genomes (related primate species: n = 5, genome size = 3 Gb), suggesting that the software is applicable to a wide variety of experimental populations. Saguaro is written in C++, runs on the Linux operating system, and can be downloaded from http://saguarogw.sourceforge.net/ webcite.