Databases of homologous gene families: new developments and web interfaces. Equipe Bioinformatique et Génomique Evolutive Laboratoire de Biométrie et Biologie Evolutive Université Claude Bernard - Lyon 1 Simon Penel, Julien Grassot, Laurent Duret, Manolo Gouy, Guy Perrière. Pôle Bio-Informatique Lyonnais

Homologous Genes Databases Research fields: Proteome/genome comparative analysis Phylogenetic studies Orthology/Paralogy relationship assignments Development of generalist databases, specialised databases –HOVERGEN: families of homologous vertebrate genes –HOBACGEN: families of homologous bacterial genes –NureBase, RTKdb, Hoppsigen, Mitalib,.. Important regions identification in genomic sequences Evolution at the molecular level Species phylogeny Function prediction

Extension of HOVERGEN and HOBACGEN to all organisms for which the complete genome sequence has been determined Structured under the ACNUC (M. Gouy) retrieval system: flat file & index files Integrates : –Protein multiple alignments –Phylogenetic trees –Taxonomic data –Nucleic and protein sequences –Sequence annotations The HoGenom database: Homologous Genes Families of fully Sequenced Organisms European project TEMBLOR

Building of HoGenom Selection of fully sequenced organisms protein sequences on the EBI proteome site. Sequence comparison with BLAST on the whole sequences dataset Clustering of the sequences in genes family on the basis of sequence similarity (transitive association) Add the gene family info in the protein sequence annotations EMBL cross references calculations, nucleotide sequences selection Add gene family info in the EMBL/GenBank nucleotide annotations Protein Alignments Phylogenetic trees ACNUC Protein database ACNUC Nucleotide database For each family

Hogenprot: Q9DCD0 ID Q9DCD0 PRELIMINARY; PRT; 483 AA. AC Q9DCD0; DT 01-JUN-2001 (TrEMBLrel. 17, Created) DT 01-JUN-2001 (TrEMBLrel. 17, Last sequence update) DT 01-MAR-2002 (TrEMBLrel. 20, Last annotation update) DE A05RIK PROTEIN. GN A05RIK. OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Rodentia; Sciurognathi; Muridae; Murinae; Mus. OX NCBI_TaxID=10090 RN [1] RP SEQUENCE FROM N.A. RC STRAIN=C57BL/6J; TISSUE=KIDNEY; RX MEDLINE= ; PubMed= ; RA Kawai J., Shinagawa A., Shibata K., Yoshino M., Itoh M., Ishii Y., ---- RA Hayashizaki Y.; RT "Functional annotation of a full-length mouse cDNA collection."; RL Nature 409: (2001). CC -!- CATALYTIC ACTIVITY: 6-PHOSPHO-D-GLUCONATE + NADP(+) = D-RIBULOSE CC 5-PHOSPHATE + CO(2) + NADPH. CC -!- PATHWAY: HEXOSE MONOPHOSPHATE SHUNT. CC -!- SIMILARITY: BELONGS TO THE 6-PHOSPHOGLUCONATE DEHYDROGENASE CC FAMILY. CC -!- GENE_FAMILY: HBG [ FAMILY / ALN / TREE ] DR EMBL; AK002894; BAB ; -. DR HSSP; P00349; 2PGD. DR MGD; MGI: ; A05Rik. DR InterPro; IPR001744; 6PGD. DR Pfam; PF00393; 6PGD; 1. DR PRINTS; PR00076; 6PGDHDRGNASE. DR PROSITE; PS00461; 6PGD; 1. DR PRODOM; Q9DCD0. DR SWISS-2DPAGE; Q9DCD0. KW NADP; Oxidoreductase; Pentose shunt. FT DOMAIN 5 60 PRODOM:2001.3:PD FT DOMAIN PRODOM:2001.3:PD FT DOMAIN PRODOM:2001.3:PD SQ SEQUENCE 483 AA; MW; CD0A3F72EEC2831E CRC64; Protein sequence annotations

Hogennucl: AK PE1 AK PE1 Location/Qualifiers FT CDS_pept FT /codon_start=1 FT /db_xref="MGD:MGI: " FT /db_xref="SWISS-PROT:Q9DCD0" FT /note="data source:SPTR, source key:P52209, evidence:ISS" FT /note="homolog to 6-PHOSPHOGLUCONATE DEHYDROGENASE, FT DECARBOXYLATING (EC )" FT /note="putative" FT /transl_table=1 FT /gene_family="HBG000005" FT /protein_id="BAB " FT /translation="MAQADIALIGLAVMGQNLILNMNDHGFVVCAFNRTVSKVDDFLAN FT EAKGTKVVGAQSLKDMVSKLKKPRRVILLVKAGQAVDDFIEKLVPLLDTGDIIIDGGNS FT EYRDTTRRCRDLKAKGILFVGSGVSGGEEGARYGPSLMPGGNKEAWPHIKAIFQAIAAK FT VGTGEPCCDWVGDEGAGHFVKMVHNGIEYGDMQLICEAYHLMKDVLGMRHEEMAQAFEE FT WNKTELDSFLIEITANILKYRDTDGKELLPKIRDSAGQKGTGKWTAISALEYGMPVTLI FT GEAVFARCLSSLKEERVQASQKLKGPKVVQLEGSKKSFLEDIRKALYASKIISYAQGFM FT LLRQAATEFGWTLNYGGIALMWRGGCIIRSVFLGKIKDAFERNPELQNLLLDDFFKSAV FT DNCQDSWRRVISTGVQAGIPMPCFTTALSFYDGYRHEMLPANLIQAQRDYFGAHTYELL FT TKPGEFIHTNWTGHGGSVSSSSYNA" atggcccaag ctgacattgc actgatcgga ctggctgtca tgggccagaa cttaattttg 60 aacatgaatg atcatggatt tgtggtctgt gctttcaata ggacagtctc caaagtcgat 120 …. ccctgcttca ctactgccct ctccttctat gatgggtaca gacacgagat gctgccagca 1320 aacctcatcc aggctcaacg ggattacttt ggggctcaca cctatgaact cttaaccaaa 1380 ccgggagaat ttatccacac caactggacg ggccacgggg gcagtgtgtc atcctcttca 1440 tacaatgcct ag 1452 // Nucleotide sequence annotations

HoGenom ACNUC contents 8th September 2003 HoGenom Proteins 423,577 sequences HoGenom Nucleotide Sequences 448,582 cds 117 fully sequenced organisms Data Source Protein data from EBI: non-redondant complete proteome sets (SWISS-PROT, TrEMBL, TrEMBLnew) June 2003 Genomic data from EMBL, June 2003

117 organisms protein sequences Arabidopsis thaliana (plant) Caenorhabditis elegans (nematod) Drosophila melanogaster (fly) Encephalitozoon cuniculi (microsporidia) Guillardia theta (alguae) Homo sapiens (man) Mus musculus (mouse) Rattus norvegicus (rat) Saccharomyces cerevisiae (yeast) Schizosaccharomyces pombe (fungus) 31% 9% 60%

families protein sequences Sequences belonging to a family (72%) Orphan Sequences (27%)

Access to HoGenom is available at the PBIL: Web page of HoGenom :

Databases Access on the Web Two main www interfaces WWW Query –Multiple query on sequences (Guy Perrière) –Multiple query on families – Cross Taxa –Search of families in function of complex taxonomic criteria –Selection of families –

Cross Taxa: Selection of Gene Families example : selecting families of animal specific genes A list of families

√ √

display family

Family Page

Application to other databases Any sequence database can be structured under ACNUC and queried with WWW-Query Currently available : SWISS-PROT, EMBL, GenBank, etc. Any family database can be structured under ACNUC and queried with WWW-Query and Cross-Taxa For example, an ACNUC version of the HAMAP database developed by SWISS-PROT is currently available at the PBIL

Example: sequence Q8ZY16 in NiceProt : cross-references to HAMAP-ACNUC and HOBACGEN Cross-references with external databases 1 sequence associated family Display the family, alignment and phylogenetic tree associated to an sequence accession number via a URL link. http

Acknowledgements People from BBE: SWISS-PROT group Laurent Duret Alexandre Gattiker Manolo Gouy Julien Grassot Simon Penel Guy Perrière This project is supported by o the European Commission (TEMBLOR) o the Rhône-Alpes region (Projet Thématiques Prioritaires)