An Integrative Method for Accurate Comparative Genome Mapping

Abstract

We present MAGIC, an integrative and accurate method for comparative genome mapping. Our method consists of two phases: preprocessing for identifying “maximal similar segments,” and mapping for clustering and classifying these segments. MAGIC's main novelty lies in its biologically intuitive clustering approach, which aims towards both calculating reorder-free segments and identifying orthologous segments. In the process, MAGIC efficiently handles ambiguities resulting from duplications that occurred before the speciation of the considered organisms from their most recent common ancestor. We demonstrate both MAGIC's robustness and scalability: the former is asserted with respect to its initial input and with respect to its parameters' values. The latter is asserted by applying MAGIC to distantly related organisms and to large genomes. We compare MAGIC to other comparative mapping methods and provide detailed analysis of the differences between them. Our improvements allow a comprehensive study of the diversity of genetic repertoires resulting from large-scale mutations, such as indels and duplications, including explicitly transposable and phagic elements. The strength of our method is demonstrated by detailed statistics computed for each type of these large-scale mutations. MAGIC enabled us to conduct a comprehensive analysis of the different forces shaping prokaryotic genomes from different clades, and to quantify the importance of novel gene content introduced by horizontal gene transfer relative to gene duplication in bacterial genome evolution. We use these results to investigate the breakpoint distribution in several prokaryotic genomes.

Precise detection of rearrangement breakpoints in mammalian chromosomes

“…Methods for identifying orthologous markers and for constructing synteny blocks are numerous in the scientific literature, starting with blocks built from physical or genetic maps of the chromosomes [ 19 ], to conserved segments of genes or blocks grouping genomic markers from whole genomic alignments [ 20 - 30 ]. The method to refine breakpoints described in the previous section requires two properties of the synteny blocks.…”

Primary orthologs from local sequence context

“…The first conceptual definition to capture the gist of the problem might have been "positional ortholog" as articulated by (Koski et al 2001) and a little bit later by (Swidan et al 2006); a similar notion of "positional homolog" was proposed by (Bourque et al 2005) and (Burgetz et al 2006). Swidan et al remark that "positional orthologs are orthologs that have preserved their relative positioning or genomic contexts in the genomes," suggesting a criterion to assess positional orthology, namely context-the sequences of their flanking regions.…”

Rapid Core-Genome Alignment and Visualization for Thousands of Intraspecific Microbial Genomes

“…[25]) to reveal their evolutionary history [26,27]. While several tools exist (LS-BSR [28], Magic[29], Mavid[30], Mauve [31–33], MGA [34], M-GCAT [35], Mugsy [36], TBA [37], multi-LAGAN [38], PECAN [39]), multiple genome alignment remains a challenging task due to the prevalence of horizontal gene transfer [40,41], recombination, homoplasy, gene conversion, mobile genetic elements, pseudogenization, and convoluted orthology relationships [25]. In addition, the computational burden of multiple sequence alignment remains very high [42] despite recent progress [43].…”