MOTIVATION: Understanding gene regulation in Plasmodium, the causative agent of malaria, is an important step in deciphering its complex life cycle as well as leading to possible new targets for therapeutic applications. Very little is known about gene regulation in Plasmodium, and in particular, few regulatory elements have been identified. Such discovery has been significantly hampered by the high A-T content of some of the genomes of Plasmodium species, as well as the challenge in associating discovered regulatory elements to gene regulatory cascades due to Plasmodium's complex life cycle. RESULTS: We report a new method of using comparative genomics to systematically discover motifs in Plasmodium without requiring any functional data. Different from previous methods, our method does not depend on sequence alignments, and thus is particularly suitable for highly divergent genomes. We applied our method to discovering regulatory motifs between the human parasite, P.falciparum, and its rodent-infectious relative, P.yoelii. We also tested our procedure against comparisons between P.falciparum and the primate-infectious, P.knowlesi. Our computational effort leads to an initial catalog of 38 distinct motifs, corresponding to over 16 200 sites in the Plasmodium genome. The functionality of these motifs was further supported by their defined distribution within the genome as well as a correlation with gene expression patterns. This initial map provides a systematic view of gene regulation in Plasmodium, which can be refined as additional genomes become available. AVAILABILITY: The new algorithm, named motif discovery using orthologous sequences (MDOS), is available at http://www.ics.uci.edu/ approximately xhx/project/mdos/.
MOTIVATION: Understanding gene regulation in Plasmodium, the causative agent of malaria, is an important step in deciphering its complex life cycle as well as leading to possible new targets for therapeutic applications. Very little is known about gene regulation in Plasmodium, and in particular, few regulatory elements have been identified. Such discovery has been significantly hampered by the high A-T content of some of the genomes of Plasmodium species, as well as the challenge in associating discovered regulatory elements to gene regulatory cascades due to Plasmodium's complex life cycle. RESULTS: We report a new method of using comparative genomics to systematically discover motifs in Plasmodium without requiring any functional data. Different from previous methods, our method does not depend on sequence alignments, and thus is particularly suitable for highly divergent genomes. We applied our method to discovering regulatory motifs between the human parasite, P.falciparum, and its rodent-infectious relative, P.yoelii. We also tested our procedure against comparisons between P.falciparum and the primate-infectious, P.knowlesi. Our computational effort leads to an initial catalog of 38 distinct motifs, corresponding to over 16 200 sites in the Plasmodium genome. The functionality of these motifs was further supported by their defined distribution within the genome as well as a correlation with gene expression patterns. This initial map provides a systematic view of gene regulation in Plasmodium, which can be refined as additional genomes become available. AVAILABILITY: The new algorithm, named motif discovery using orthologous sequences (MDOS), is available at http://www.ics.uci.edu/ approximately xhx/project/mdos/.
Authors: Alexander Stark; Michael F Lin; Pouya Kheradpour; Jakob S Pedersen; Leopold Parts; Joseph W Carlson; Madeline A Crosby; Matthew D Rasmussen; Sushmita Roy; Ameya N Deoras; J Graham Ruby; Julius Brennecke; Emily Hodges; Angie S Hinrichs; Anat Caspi; Benedict Paten; Seung-Won Park; Mira V Han; Morgan L Maeder; Benjamin J Polansky; Bryanne E Robson; Stein Aerts; Jacques van Helden; Bassem Hassan; Donald G Gilbert; Deborah A Eastman; Michael Rice; Michael Weir; Matthew W Hahn; Yongkyu Park; Colin N Dewey; Lior Pachter; W James Kent; David Haussler; Eric C Lai; David P Bartel; Gregory J Hannon; Thomas C Kaufman; Michael B Eisen; Andrew G Clark; Douglas Smith; Susan E Celniker; William M Gelbart; Manolis Kellis Journal: Nature Date: 2007-11-08 Impact factor: 49.962
Authors: Jane M Carlton; Samuel V Angiuoli; Bernard B Suh; Taco W Kooij; Mihaela Pertea; Joana C Silva; Maria D Ermolaeva; Jonathan E Allen; Jeremy D Selengut; Hean L Koo; Jeremy D Peterson; Mihai Pop; Daniel S Kosack; Martin F Shumway; Shelby L Bidwell; Shamira J Shallom; Susan E van Aken; Steven B Riedmuller; Tamara V Feldblyum; Jennifer K Cho; John Quackenbush; Martha Sedegah; Azadeh Shoaibi; Leda M Cummings; Laurence Florens; John R Yates; J Dale Raine; Robert E Sinden; Michael A Harris; Deirdre A Cunningham; Peter R Preiser; Lawrence W Bergman; Akhil B Vaidya; Leo H van Lin; Chris J Janse; Andrew P Waters; Hamilton O Smith; Owen R White; Steven L Salzberg; J Craig Venter; Claire M Fraser; Stephen L Hoffman; Malcolm J Gardner; Daniel J Carucci Journal: Nature Date: 2002-10-03 Impact factor: 49.962
Authors: Yingyao Zhou; Vandana Ramachandran; Kota Arun Kumar; Scott Westenberger; Phillippe Refour; Bin Zhou; Fengwu Li; Jason A Young; Kaisheng Chen; David Plouffe; Kerstin Henson; Victor Nussenzweig; Jane Carlton; Joseph M Vinetz; Manoj T Duraisingh; Elizabeth A Winzeler Journal: PLoS One Date: 2008-02-13 Impact factor: 3.240
Authors: Douglas H Sieglaff; W Augustine Dunn; Xiaohui S Xie; Karyn Megy; Osvaldo Marinotti; Anthony A James Journal: Proc Natl Acad Sci U S A Date: 2009-02-11 Impact factor: 11.205
Authors: Tracey L Campbell; Erandi K De Silva; Kellen L Olszewski; Olivier Elemento; Manuel Llinás Journal: PLoS Pathog Date: 2010-10-28 Impact factor: 6.823
Authors: Sanne Nygaard; Alexander Braunstein; Gareth Malsen; Stijn Van Dongen; Paul P Gardner; Anders Krogh; Thomas D Otto; Arnab Pain; Matthew Berriman; Jon McAuliffe; Emmanouil T Dermitzakis; Daniel C Jeffares Journal: PLoS Genet Date: 2010-09-09 Impact factor: 5.917