1. 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

2. 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

3. 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

4. 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

5. 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 0610042A05RIK PROTEIN. GN 0610042A05RIK. 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=21085660; PubMed=11217851; 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 409:685-690(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: HBG000005 [ FAMILY / ALN / TREE ] DR EMBL; AK002894; BAB22439.1; -. DR HSSP; P00349; 2PGD. DR MGD; MGI:1914101; 0610042A05Rik. 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:PD001594 134 FT DOMAIN 63 296 PRODOM:2001.3:PD001025 91 FT DOMAIN 316 469 PRODOM:2001.3:PD001549 79 SQ SEQUENCE 483 AA; 53247 MW; CD0A3F72EEC2831E CRC64; Protein sequence annotations

6. Hogennucl: AK002894.PE1 AK002894.PE1 Location/Qualifiers FT CDS_pept 76..1527 FT /codon_start=1 FT /db_xref="MGD:MGI:1914101" 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 1.1.1.44)" FT /note="putative" FT /transl_table=1 FT /gene_family="HBG000005" FT /protein_id="BAB22439.1" 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

7. 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) http://www.ebi.ac.uk/proteome, June 2003 Genomic data from EMBL, June 2003

8. 117 organisms 423 577 protein sequences 1016 91 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%

9. 41 907 families 423 577 protein sequences Sequences belonging to a family 305 514 (72%) 305 514 115 373 Orphan Sequences (27%) 115 373

10. Access to HoGenom is available at the PBIL: http://pbil.univ-lyon1.fr/ Web page of HoGenom : http://pbil.univ-lyon1.fr/databases/hogenom.html

11. Databases Access on the Web Two main www interfaces WWW Query –Multiple query on sequences (Guy Perrière) –Multiple query on families –http://pbil.univ-lyon1.fr/search/query_fam.phphttp://pbil.univ-lyon1.fr/search/query_fam.php Cross Taxa –Search of families in function of complex taxonomic criteria –Selection of families –http://pbil.univ-lyon1.fr/search/cross_fam.phphttp://pbil.univ-lyon1.fr/search/cross_fam.php

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

13. √ √

14. display family

15. Family Page

17. 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

18. 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 http://pbil.univ-lyon1.fr/cgi-bin/acnuc-link-ac2fam?db=HAMAPprot&query=Q8ZY16

19. 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)