MetaMine--a tool to detect and analyse gene patterns in their environmental context.

BACKGROUND: Modern sequencing technologies allow rapid sequencing and bioinformatic analysis of genomes and metagenomes. With every new sequencing project a vast number of new proteins become available with many genes remaining functionally unclassified based on evidences from sequence similarities alone. Extending similarity searches with gene pattern approaches, defined as genes sharing a distinct genomic neighbourhood, have shown to significantly improve the number of functional assignments. Further functional evidences can be gained by correlating these gene patterns with prevailing environmental parameters. MetaMine was developed to approach the large pool of unclassified proteins by searching for recurrent gene patterns across habitats based on key genes. RESULTS: MetaMine is an interactive data mining tool which enables the detection of gene patterns in an environmental context. The gene pattern search starts with a user defined environmentally interesting key gene. With this gene a BLAST search is carried out against the Microbial Ecological Genomics DataBase (MEGDB) containing marine genomic and metagenomic sequences. This is followed by the determination of all neighbouring genes within a given distance and a search for functionally equivalent genes. In the final step a set of common genes present in a defined number of distinct genomes is determined. The gene patterns found are associated with their individual pattern instances describing gene order and directions. They are presented together with information about the sample and the habitat. MetaMine is implemented in Java and provided as a client/server application with a user-friendly graphical user interface. The system was evaluated with environmentally relevant genes related to the methane-cycle and carbon monoxide oxidation. CONCLUSION: MetaMine offers a targeted, semi-automatic search for gene patterns based on expert input. The graphical user interface of MetaMine provides a user-friendly overview of the computed gene patterns for further inspection in an ecological context. Prevailing biological processes associated with a key gene can be used to infer new annotations and shape hypotheses to guide further analyses. The use-cases demonstrate that meaningful gene patterns can be quickly detected using MetaMine.MetaMine is freely available for academic use from http://www.megx.net/metamine.

PhyloGena--a user-friendly system for automated phylogenetic annotation of unknown sequences.

MOTIVATION: Phylogenomic approaches towards functional and evolutionary annotation of unknown sequences have been suggested to be superior to those based only on pairwise local alignments. User-friendly software tools making the advantages of phylogenetic annotation available for the ever widening range of bioinformatically uninitiated biologists involved in genome/EST annotation projects are, however, not available. We were particularly confronted with this issue in the annotation of sequences from different groups of complex algae originating from secondary endosymbioses, where the identification of the phylogenetic origin of genes is often more problematic than in taxa well represented in the databases (e.g. animals, plants or fungi). RESULTS: We present a flexible pipeline with a user-friendly, interactive graphical user interface running on desktop computers that automatically performs a basic local alignment search tool (BLAST) search of query sequences, selects a representative subset of them, then creates a multiple alignment from the selected sequences, and finally computes a phylogenetic tree. The pipeline, named PhyloGena, uses public domain software for all standard bioinformatics tasks (similarity search, multiple alignment, and phylogenetic reconstruction). As the major technological innovation, selection of a meaningful subset of BLAST hits was implemented using logic programming, mimicing the selection procedure (BLAST tables, multiple alignments and phylogenetic trees) are displayed graphically, allowing the user to interact with the pipeline and deduce the function and phylogenetic origin of the query. PhyloGena thus makes phylogenomic annotation available also for those biologists without access to large computing facilities and with little informatics background. Although phylogenetic annotation is particularly useful when working with composite genomes (e.g. from complex algae), PhyloGena can be helpful in expressed sequence tag and genome annotation also in other organisms. AVAILABILITY: PhyloGena (executables for LINUX and Windows 2000/XP as well as source code) is available by anonymous ftp from http://www.awi.de/en/phylogena.