BINF8210-Fall2009 - ComputationalncRNAgenefinding...

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C omputational ncRNA gene finding (&  nc RNA structure prediction)   Liming Cai    (BINF8210@UGA, Fall 2009)  nc RNA structure prediction   (& computational ncRNA gene  finding)
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Non-coding RNAs • Functions other than coding proteins,  e.g., structural, catalytic, and  regulatory factors functional RNAs = ncRNAs + UTR motifs • (-) No strong statistical features, such  as ORFs, or polyadenylated, demonstrated  in coding genes • (+) Transcribed ncRNA molecules can fold  into secondary and tertiary structures  (more conserved than sequences)
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Sources of ncRNAs • Non-coding RNA genes encode RNAs, e.g.,  miRNAs, rox1 and rox2 RNAs in male  Drosophila melanogaster . • In introns and intergenic regions, e.g.,  snoRNAs • In 5’ and 3’ UTRs, e.g., regulatory  motifs (functional RNAs)
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Functions of ncRNAs • rRNAs and tRNAs • RNA maturation: snRNA in recognizing  splicing sites • RNA modification: snoRNA converting  uridine to pseudo-uridine • Regulation of gene expression and  translation: e.g., miRNAs • DNA replication: e.g., telomerase RNAs -  template for addition of telomeric  repeats • Etc.
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Classes of ncRNAs (Bompfunewerer, et al, 2005) Class Size Function Phylogenetic distribution tRNA 70-80 Translation ubiquitous rRNA 16S/18S 28S+5.8S/23S 5S 1.5K 3K 130 translation ubiquitous RNase P MRP 220-440 250-350 tRNA -maturation ubiquitous eukarya snoRNA telomerase 130 400-550 pseudouridinyl ation addition of repeats snRNA U1 ~ U6 100-600 130-140 Spliceosome mRNA maturation Eukarya Eukarya, archaea U7 ~65 Histone mRNA Eukayotes
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Some ncRNAs databases • Rfam (280,000 regions of 379 families) • NONCODE (109 transitional classes and 9  groups)  • RNAdb (800 mammalian ncRNAs, excluding  tRNAs, rRNAs and snRNAs) • Arabidposis small RNA Project (ASRP) • Etc.
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ncRNA gene finding strategies 1. Computational predictive methods  2. cDNA cloning to enrich ncRNAs 3. Detecting new transcripts with  oligonucleotide microarrays
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ncRNA gene finding:  a computational challenge • ncRNA genes do not have significant  statistical signals • large in number • diverse, 20 nts to 22,000 nts - Not sure what to look for - Computationally intensive - Simply no good method - Methods compromising  accuracy 
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Computational ncRNA gene finding  methods Specific (custom-designed) ncRNA search and  annotation (e.g., tRNAscan, methylattion-guide snoRNA,  miRNA, tmRNA) Reconfigurable search systems (e.g., SCFG, CM,  ERPIN) – mechanism to profile the target ncRNA (structure) -  need training data De novo ncRNA gene detection with – base composition (e.g., G+C %) – structure fold (e.g., RNAFold) Comparative analysis (e.g., QRNA, EvolFold) - consensus structure  ncRNA “holy grail” ?
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Review literature in computational  ncRNA gene finding and annotation A. Laederach (2007) Informatics challenges in 
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BINF8210-Fall2009 - ComputationalncRNAgenefinding...

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