BackgroundA rapidly increasing flow of genomic data requires the development of efficient methods for obtaining its compact representation. Feature extraction facilitates classification, clustering and model analysis for testing and refining biological hypotheses. “Shotgun” metagenome is an analytically challenging type of genomic data - containing sequences of all genes from the totality of a complex microbial community. Recently, researchers started to analyze metagenomes using reference-free methods based on the analysis of oligonucleotides (k-mers) frequency spectrum previously applied to isolated genomes. However, little is known about their correlation with the existing approaches for metagenomic feature extraction, as well as the limits of applicability. Here we evaluated a metagenomic pairwise dissimilarity measure based on short k-mer spectrum using the example of human gut microbiota, a biomedically significant object of study.ResultsWe developed a method for calculating pairwise dissimilarity (beta-diversity) of “shotgun” metagenomes based on short k-mer spectra (5≤k≤11). The method was validated on simulated metagenomes and further applied to a large collection of human gut metagenomes from the populations of the world (n=281). The k-mer spectrum-based measure was found to behave similarly to one based on mapping to a reference gene catalog, but different from one using a genome catalog. This difference turned out to be associated with a significant presence of viral reads in a number of metagenomes. Simulations showed limited impact of bacterial genetic variability as well as sequencing errors on k-mer spectra. Specific differences between the datasets from individual populations were identified.ConclusionsOur approach allows rapid estimation of pairwise dissimilarity between metagenomes. Though we applied this technique to gut microbiota, it should be useful for arbitrary metagenomes, even metagenomes with novel microbiota. Dissimilarity measure based on k-mer spectrum provides a wider perspective in comparison with the ones based on the alignment against reference sequence sets. It helps not to miss possible outstanding features of metagenomic composition, particularly related to the presence of an unknown bacteria, virus or eukaryote, as well as to technical artifacts (sample contamination, reads of non-biological origin, etc.) at the early stages of bioinformatic analysis. Our method is complementary to reference-based approaches and can be easily integrated into metagenomic analysis pipelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0875-7) contains supplementary material, which is available to authorized users.

The demographic history of any population is imprinted in the genomes of the individuals that make up the population. One of the most popular and convenient representations of genetic information is the allele frequency spectrum or AFS, the distribution of allele frequencies in populations. The joint allele frequency spectrum is commonly used to reconstruct the demographic history of multiple populations and several methods based on diffusion approximation (e.g., ∂a∂i) and ordinary differential equations (e.g., moments) have been developed and applied for demographic inference. These methods provide an opportunity to simulate AFS under a variety of researcher-specified demographic models and to estimate the best model and associated parameters using likelihood-based local optimizations. However, there are no known algorithms to perform global searches of demographic models with a given AFS.Here, we introduce a new method that implements a global search using a genetic algorithm for the automatic and unsupervised inference of demographic history from joint allele frequency spectrum data.Our method is implemented in the software GADMA (Genetic Algorithm for Demographic Analysis, https://github.com/ctlab/GADMA). We demonstrate the performance of GADMA by applying it to sequence data from humans and non-model organisms and show that it is able to automatically infer a demographic model close to or even better than the one that was previously obtained manually. Moreover, GADMA is able to infer demographic models at different local optima close to the global one, making it is possible to detect more biology corrected model during further research.

Background The demographic history of any population is imprinted in the genomes of the individuals that make up the population. One of the most popular and convenient representations of genetic information is the allele frequency spectrum (AFS), the distribution of allele frequencies in populations. The joint AFS is commonly used to reconstruct the demographic history of multiple populations, and several methods based on diffusion approximation (e.g., ∂a∂i) and ordinary differential equations (e.g., moments) have been developed and applied for demographic inference. These methods provide an opportunity to simulate AFS under a variety of researcher-specified demographic models and to estimate the best model and associated parameters using likelihood-based local optimizations. However, there are no known algorithms to perform global searches of demographic models with a given AFS. Results Here, we introduce a new method that implements a global search using a genetic algorithm for the automatic and unsupervised inference of demographic history from joint AFS data. Our method is implemented in the software GADMA (Genetic Algorithm for Demographic Model Analysis, https://github.com/ctlab/GADMA). Conclusions We demonstrate the performance of GADMA by applying it to sequence data from humans and non-model organisms and show that it is able to automatically infer a demographic model close to or even better than the one that was previously obtained manually. Moreover, GADMA is able to infer multiple demographic models at different local optima close to the global one, providing a larger set of possible scenarios to further explore demographic history.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.