Whole genome evaluation of horizontal transfers in the pathogenic fungus Aspergillus fumigatus

<p>Abstract</p> <p>Background</p> <p>Numerous cases of horizontal transfers (HTs) have been described for eukaryote genomes, but in contrast to prokaryote genomes, no whole genome evaluation of HTs has been carried out. This is mainly due to a lack of parametric methods specially designed to take the intrinsic heterogeneity of eukaryote genomes into account. We applied a simple and tested method based on local variations of genomic signatures to analyze the genome of the pathogenic fungus <it>Aspergillus fumigatus</it>.</p> <p>Results</p> <p>We detected 189 atypical regions containing 214 genes, accounting for about 1 Mb of DNA sequences. However, the fraction of atypical DNA detected was smaller than the average amount detected in the same conditions in prokaryote genomes (3.1% vs 5.6%). It appeared that about one third of these regions contained no annotated genes, a proportion far greater than in prokaryote genomes. When analyzing the origin of these HTs by comparing their signatures to a home made database of species signatures, 3 groups of donor species emerged: bacteria (40%), fungi (25%), and viruses (22%). It is to be noticed that though inter-domain exchanges are confirmed, we only put in evidence very few exchanges between eukaryotic kingdoms.</p> <p>Conclusions</p> <p>In conclusion, we demonstrated that HTs are not negligible in eukaryote genomes, bearing in mind that in our stringent conditions this amount is a floor value, though of a lesser extent than in prokaryote genomes. The biological mechanisms underlying those transfers remain to be elucidated as well as the biological functions of the transferred genes.</p

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

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

Exploration of phylogenetic data using a global sequence analysis method

BACKGROUND: Molecular phylogenetic methods are based on alignments of nucleic or peptidic sequences. The tremendous increase in molecular data permits phylogenetic analyses of very long sequences and of many species, but also requires methods to help manage large datasets. RESULTS: Here we explore the phylogenetic signal present in molecular data by genomic signatures, defined as the set of frequencies of short oligonucleotides present in DNA sequences. Although violating many of the standard assumptions of traditional phylogenetic analyses – in particular explicit statements of homology inherent in character matrices – the use of the signature does permit the analysis of very long sequences, even those that are unalignable, and is therefore most useful in cases where alignment is questionable. We compare the results obtained by traditional phylogenetic methods to those inferred by the signature method for two genes: RAG1, which is easily alignable, and 18S RNA, where alignments are often ambiguous for some regions. We also apply this method to a multigene data set of 33 genes for 9 bacteria and one archea species as well as to the whole genome of a set of 16 γ-proteobacteria. In addition to delivering phylogenetic results comparable to traditional methods, the comparison of signatures for the sequences involved in the bacterial example identified putative candidates for horizontal gene transfers. CONCLUSION: The signature method is therefore a fast tool for exploring phylogenetic data, providing not only a pretreatment for discovering new sequence relationships, but also for identifying cases of sequence evolution that could confound traditional phylogenetic analysis

ColorPhylo: A Color Code to Accurately Display Taxonomic Classifications

Color may be very useful to visualise complex data. As far as taxonomy is concerned, color may help observing various species’ characteristics in correlation with classification. However, choosing the number of subclasses to display is often a complex task: on the one hand, assigning a limited number of colors to taxa of interest hides the structure imbedded in the subtrees of the taxonomy; on the other hand, differentiating a high number of taxa by giving them specific colors, without considering the underlying taxonomy, may lead to unreadable results since relationships between displayed taxa would not be supported by the color code. In the present paper, an automatic color coding scheme is proposed to visualise the levels of taxonomic relationships displayed as overlay on any kind of data plot. To achieve this goal, a dimensionality reduction method allows displaying taxonomic “distances” onto a Euclidean two-dimensional space. The resulting map is projected onto a 2D color space (the Hue, Saturation, Brightness colorimetric space with brightness set to 1). Proximity in the taxonomic classification corresponds to proximity on the map and is therefore materialised by color proximity. As a result, each species is related to a color code showing its position in the taxonomic tree. The so called ColorPhylo displays taxonomic relationships intuitively and can be combined with any biological result. A Matlab version of ColorPhylo is available at http://sy.lespi.free.fr/ColorPhylo-homepage.html. Meanwhile, an ad-hoc distance in case of taxonomy with unknown edge lengths is proposed

Chaos game representation for comparison of whole genomes

BACKGROUND: Chaos game representation of genome sequences has been used for visual representation of genome sequence patterns as well as alignment-free comparisons of sequences based on oligonucleotide frequencies. However the potential of this representation for making alignment-based comparisons of whole genome sequences has not been exploited. RESULTS: We present here a fast algorithm for identifying all local alignments between two long DNA sequences using the sequence information contained in CGR points. The local alignments can be depicted graphically in a dot-matrix plot or in text form, and the significant similarities and differences between the two sequences can be identified. We demonstrate the method through comparison of whole genomes of several microbial species. Given two closely related genomes we generate information on mismatches, insertions, deletions and shuffles that differentiate the two genomes. CONCLUSION: Addition of the possibility of large scale sequence alignment to the repertoire of alignment-free sequence analysis applications of chaos game representation, positions CGR as a powerful sequence analysis tool

Biological sequences as pictures – a generic two dimensional solution for iterated maps

<p>Abstract</p> <p>Background</p> <p>Representing symbolic sequences graphically using iterated maps has enjoyed an enduring popularity since it was first proposed in Jeffrey 1990 as chaos game representation (CGR). The usefulness of this representation goes beyond the convenience of a scale independent representation. It provides a variable memory length representation of transition. This includes the representation of succession with non-integer order, which comes with the promise of generalizing Markovian formalisms. The original proposal targeted genomic sequences only but since then several generalizations have been proposed, many specifically designed to handle protein data.</p> <p>Results</p> <p>The challenge of a general solution is that of deriving a bijective transformation of symbolic sequences into bi-dimensional planes. More specifically, it requires the regular fractal nesting of polygons. A first attempt at a general solution was proposed by Fiser 1994 by using non-overlapping circles that contain the polygons. This was used as a starting point to identify a more efficient solution where the encapsulating circles can overlap without the same happening for the sequence maps which are circumscribed to fractal polygon domains.</p> <p>Conclusion</p> <p>We identified the optimal inscribed packing solution for iterated maps of any Biological sequence, indeed of any symbolic sequence. The new solution maintains the prized bijective mapping property and includes the Sierpinski triangle and the CGR square as particular solutions of the more encompassing formulation.</p

PHACTS, a computational approach to classifying the lifestyle of phages

Motivation: Bacteriophages have two distinct lifestyles: virulent and temperate. The virulent lifestyle has many implications for phage therapy, genomics and microbiology. Determining which lifestyle a newly sequenced phage falls into is currently determined using standard culturing techniques. Such laboratory work is not only costly and time consuming, but also cannot be used on phage genomes constructed from environmental sequencing. Therefore, a computational method that utilizes the sequence data of phage genomes is needed

A Benchmark of Parametric Methods for Horizontal Transfers Detection

Horizontal gene transfer (HGT) has appeared to be of importance for prokaryotic species evolution. As a consequence numerous parametric methods, using only the information embedded in the genomes, have been designed to detect HGTs. Numerous reports of incongruencies in results of the different methods applied to the same genomes were published. The use of artificial genomes in which all HGT parameters are controlled allows testing different methods in the same conditions. The results of this benchmark concerning 16 representative parametric methods showed a great variety of efficiencies. Some methods work very poorly whatever the type of HGTs and some depend on the conditions or on the metrics used. The best methods in terms of total errors were those using tetranucleotides as criterion for the window methods or those using codon usage for gene based methods and the Kullback-Leibler divergence metric. Window methods are very sensitive but less specific and detect badly lone isolated gene. On the other hand gene based methods are often very specific but lack of sensitivity. We propose using two methods in combination to get the best of each category, a gene based one for specificity and a window based one for sensitivity

FluentDNA: Nucleotide Visualization of Whole Genomes, Annotations, and Alignments

Researchers seldom look at naked genome assemblies: instead the attributes of DNA sequences are mediated through statistics, annotations and high level summaries. Here we present software that visualizes the bare sequences of whole genome assemblies in a zoomable interface. This can assist in detection of chromosome architecture and contamination by the naked eye through changes in color patterns, in the absence of any other annotation. When available, annotations can be visualized alongside or on top of the naked sequence. Genome alignments can also be visualized, laying two genomes side by side in an alignment and highlighting their differences at nucleotide resolution. FluentDNA gives researchers direct visualization of whole genome assemblies, annotations and alignments, for quality control, hypothesis generation, and communicating results

W-Curve Alignments for HIV-1 Genomic Comparisons

The W-curve was originally developed as a graphical visualization technique for viewing DNA and RNA sequences. Its ability to render features of DNA also makes it suitable for computational studies. Its main advantage in this area is utilizing a single-pass algorithm for comparing the sequences. Avoiding recursion during sequence alignments offers advantages for speed and in-process resources. The graphical technique also allows for multiple models of comparison to be used depending on the nucleotide patterns embedded in similar whole genomic sequences. The W-curve approach allows us to compare large numbers of samples quickly.We are currently tuning the algorithm to accommodate quirks specific to HIV-1 genomic sequences so that it can be used to aid in diagnostic and vaccine efforts. Tracking the molecular evolution of the virus has been greatly hampered by gap associated problems predominantly embedded within the envelope gene of the virus. Gaps and hypermutation of the virus slow conventional string based alignments of the whole genome. This paper describes the W-curve algorithm itself, and how we have adapted it for comparison of similar HIV-1 genomes. A treebuilding method is developed with the W-curve that utilizes a novel Cylindrical Coordinate distance method and gap analysis method. HIV-1 C2-V5 env sequence regions from a Mother/Infant cohort study are used in the comparison.The output distance matrix and neighbor results produced by the W-curve are functionally equivalent to those from Clustal for C2-V5 sequences in the mother/infant pairs infected with CRF01_AE.Significant potential exists for utilizing this method in place of conventional string based alignment of HIV-1 genomes, such as Clustal X. With W-curve heuristic alignment, it may be possible to obtain clinically useful results in a short time-short enough to affect clinical choices for acute treatment. A description of the W-curve generation process, including a comparison technique of aligning extremes of the curves to effectively phase-shift them past the HIV-1 gap problem, is presented. Besides yielding similar neighbor-joining phenogram topologies, most Mother and Infant C2-V5 sequences in the cohort pairs geometrically map closest to each other, indicating that W-curve heuristics overcame any gap problem