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. 2013 May;30(5):1218-23.
doi: 10.1093/molbev/mst025. Epub 2013 Feb 14.

Detecting Sequence Homology at the Gene Cluster Level With MultiGeneBlast

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Free PMC article

Detecting Sequence Homology at the Gene Cluster Level With MultiGeneBlast

Marnix H Medema et al. Mol Biol Evol. .
Free PMC article

Abstract

The genes encoding many biomolecular systems and pathways are genomically organized in operons or gene clusters. With MultiGeneBlast, we provide a user-friendly and effective tool to perform homology searches with operons or gene clusters as basic units, instead of single genes. The contextualization offered by MultiGeneBlast allows users to get a better understanding of the function, evolutionary history, and practical applications of such genomic regions. The tool is fully equipped with applications to generate search databases from GenBank or from the user's own sequence data. Finally, an architecture search mode allows searching for gene clusters with novel configurations, by detecting genomic regions with any user-specified combination of genes. Sources, precompiled binaries, and a graphical tutorial of MultiGeneBlast are freely available from http://multigeneblast.sourceforge.net/.

Figures

F<sc>ig</sc>. 1.
Fig. 1.
Outline of the homology search process by MultiGeneBlast. First, the amino acid translation of each gene sequence within the query gene cluster is searched against the selected MultiGeneBlast database, yielding a data set of BLAST hits. The BLAST hits are then mapped to their parent nucleotide scaffolds, based on the information from the database. The nucleotide scaffolds are then sorted according to their empirical similarity scores with the query gene cluster. Finally, the sorted list of genomic loci is displayed in an interactive XHTML file that can be viewed with any modern web browser.
F<sc>ig</sc>. 2.
Fig. 2.
A user-friendly GUI allows easy construction of databases and easy use of the program. (A) User-friendly selection of input files and databases. (B) Direct download of GenBank entries from NCBI and simple button to download MultiGeneBlast-reformatted GenBank database. (C) Options to design databases from files, from online GenBank entries or from entire GenBank divisions. (D) Link to the MultiGeneBlast website with help pages, a tutorial, and various downloads.
F<sc>ig</sc>. 3.
Fig. 3.
Example output of a MultiGeneBlast run. The output consists of an interactive XHTML page, in which additional information on each gene appears on mouse-over or by clicking on a gene. This feature works for colored homologous genes and white nonhomologous genes. The first example output shown here displays a homology search for the coumermycin biosynthetic gene cluster, which identifies gene clusters encoding related compounds. The second example output shows the power of an architecture search to find specific pathways: By using a query of a type III polyketide synthase and a terpene cyclase, biosynthetic gene clusters encoding hybrid polyketide-terpene compounds are identified straightforwardly. Single alignments of the query gene clusters with any particular hit gene cluster can also be selected from a drop-down menu. All gene cluster images are stored in SVG format, so they can easily be transformed into publication-quality figures.

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