Bréhélin et al. BMC Genomics 2010, 11:35 http://www.biomedcentral.com/1471-2164/11/35 Gene Ontology annotations (red = Molecular Function, green = Biological Process, blue = Cellular Component). Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2164-11- 35-S3.HTML ] Additional file 4: Bozdech - Spellman analysis. This file presents the cluster pairs identified as revealing a conservation of coexpression when comparing the Bozdech and Spellman data. This file also provide additional information on the available functional annotations, as well as links to the BLAST alignments and the different databases (click on the ‘?’s to access PlasmoDB, SGD, and Amigo databases). Gene functional annotations are as follows. The short description immediately following each P. falciparum gene comes from PlasmoDB (red = functional gene, blue = putative gene, black = hypothetical gene). Other annotations are Gene Ontology annotations (red = Molecular Function, green = Biological Process, blue = Cellular Component). Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2164-11- 35-S4.HTML ] Additional file 5: Bozdech - Pilot analysis. This file presents the cluster pairs identified as revealing a conservation of coexpression when comparing the Bozdech and Pilot data. This file also provide additional information on the available functional annotations, as well as links to the BLAST alignments and the different databases (click on the ‘?’s to access PlasmoDB, FlyBase, and Amigo databases). Gene functional annotations are as follows. The short description immediately following each P. falciparum gene comes from PlasmoDB (red = functional gene, blue = putative gene, black = hypothetical gene). Other annotations are Gene Ontology annotations (red = Molecular Function, green = Biological Process, blue = Cellular Component). Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2164-11- 35-S5.HTML ] Additional file 6: Predicted annotations of P. falciparum gene coding for putative ribosomal proteins (structural constituent of ribosomes, GO:0003735). Prediction gained by co-coexpression analyses compared to PlasmoDB 5.4: (0) confirmed annotation; (1) refined annotation of an incomplete or wrong original functional inference; (2) previously hypothetical; (N): no advance based on co-coexpression analyses; (+) functional inference of hypothetical gene products by Smits et al. (2007) [32]; (*) correction of Smits et al. (2007) annotation; (Z) pair also identified in Zhou et al. (2008) [15]; (x): pairing of P. falciparum and S. cerevisiae or P. falciparum and D. melanogaster genes in co- coexpression analyses. Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2164-11- 35-S6.PDF ] Additional file 7: Predicted annotations of P. falciparum gene products involved in ribosome biogenesis and assembly (GO:0042254), rRNA metabolic process (GO:0016072) and tRNA processing (GO:0008033). Prediction gained by co-coexpression analyses when compared to PlasmoDB 5.4: (0) confirmed annotation; (1) refined annotation of an incomplete or wrong original functional inference; (2) previously hypothetical; (Z) pair also identified in Zhou et al. (2008) [15]. (x): pairing of P. falciparum and S. cerevisiae or P. falciparum and D. melanogaster genes in co-coexpression analyses. (§): pairing of P. falciparum and S. cerevisiae genes in co-coexpression with different clustering parameters. (*): Correction of the gene models of PF14_0436 and PF14_0437, forming a unique gene coding for a putative nucleolar DEAD/DEAH box ATP-dependent RNA helicase (see Add. File 8). Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2164-11- 35-S7.PDF ] Additional file 8: Correction of the gene structures and functional inference of PF14_0436 and PF14_0437 based on P. falciparum vs. S. cerevisiae co-coexpression analyses. In co-coxpression analyses, both PF14_0436 and PF14_0437 were in the same expression cluster and with the same yeast sequence, YNL112W, involved in ribosome biogenesis and assembly (GO:0042254, see Add. File 7). Sequence comparison of these Page 13 of 14 contiguous predicted open reading frames shows that they align with both extremities of YNL112W, and that their overlapping region is an error of the gene model, corrected in updated versions of PlasmoDB. Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2164-11- 35-S8.PDF ] Additional file 9: Other annotations of P. falciparum gene products based on co-coexpression analyses. Prediction gained by co- coexpression analyses when compared to PlasmoDB 5.4: (0) confirmed annotation; (1) refined annotation of an incomplete or wrong original functional inference; (2) previously hypothetical; (Z) pair also identified in Zhou et al. (2008) [15]. (x): pairing of P. falciparum and S. cerevisiae or P. falciparum and D. melanogaster genes in co-coexpressed analyses. (§): pairing of P. falciparum and S. cerevisiae genes in co-coexpression with different clustering parameters. This table summarizes important functional annotation predicted for P. falciparum genes previously reported as “hypotheticals” or with little indication of a putative function. Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2164-11- 35-S9.PDF ] Acknowledgements This research is supported by the French National Research Agency (PlasmoExplore project, ANR-06-CIS6-MDCA-014). Author details 1Méthodes et algorithmes pour la Bioinformatique, LIRMM, Univ. Montpellier 2, CNRS; 161 rue Ada, 34392 MONTPELLIER, France. 2FRE3206 CNRS/MNHN, USM504, Biologie Fonctionnelle des Protozoaires, RDDM, Muséum National d’Histoire Naturelle, Paris, France. 3UMR 5168 CNRS-CEA-INRA-Grenoble Université, Institut de Recherches en Technologies et Sciences pour le Vivant, CEA-Grenoble; 17, rue des Martyrs, 38054 Grenoble, France. Authors’ contributions LB conceived, designed and implemented the method, carried out the experiments, and drafted the manuscript. IF and EM designed and analyzed the experiments and drafted the manuscript. OG revised the manuscript and initiated the project. All authors read and approved the final manuscript. Received: 10 July 2009 Accepted: 15 January 2010 Published: 15 January 2010 References 1. Tuteja R: Malaria - an overview. FEBS J 2007, 274(18):4670-4679. 2. Yeh I, Altman R: Drug Targets for Plasmodium falciparum: a post- genomic review/survey. Mini Rev Med Chem 2006, 6(2):177-202. 3. Greenwood B, Fidock D, Kyle D, Kappe S, Alonso P, Collins F, Duffy P: Malaria: progress, perils, and prospects for eradication. J Clin Invest 2008, 118(4):1266-1276. 4. Gardner M, Hall N, Fung E, White O, Berriman M, Hyman R, Carlton J, Pain A, Nelson K, Bowman S, Paulsen I, James K, Eisen J, Rutherford K, Salzberg S, Craig A, Kyes S, Chan M, Nene V, Shallom S, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather M, Vaidya A, Martin D, Fairlamb A, Fraunholz M, Roos D, Ralph S, McFadden G, Cummings L, Subramanian G, Mungall C, Venter J, Carucci D, Hoffman S, Newbold C, Davis R, Fraser C, Barrell B: Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 2002, 419(6906):498-511. 5. Adl S, Leander B, Simpson A, Archibald J, Anderson O, Bass D, Bowser S, Brugerolle G, Farmer M, Karpov S, Kolisko M, Lane C, Lodge D, Mann D, Meisterfeld R, Mendoza L, Moestrup O, Mozley-Standridge S, Smirnov A, Spiegel F: Diversity, nomenclature, and taxonomy of protists. Syst Biol 2007, 56(4):684-689. 6. Baldauf S: The deep roots of eukaryotes. Science 2003, 300(5626):1703-1706. 7. Pizzi E, Frontali C: Low-complexity regions in Plasmodium falciparum proteins. Genome Res 2001, 11(2):218-229. 8. Altschul S, Gish W, Miller W, Myers E, Lipman D: Basic local alignment search tool. J Mol Biol 1990, 215(3):403-410.