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Why N-SCAN Works Part 3 of 5,498

Why N-SCAN Works Part 3 of 5,498. Bob Zimmermann 12/14/2005 (My 25th Birthday). Why Are We Concerned?. N-SCAN works just about as well in human with one informant as it does with eight.

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Why N-SCAN Works Part 3 of 5,498

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  1. Why N-SCAN WorksPart 3 of 5,498 Bob Zimmermann 12/14/2005 (My 25th Birthday)

  2. Why Are We Concerned? • N-SCAN works just about as well in human with one informant as it does with eight. • This means N-SCAN’s fancy phylogenetic mutation rate model has little effect on the outcome of the human predictions • Not always the case (fly).

  3. What Are We Doing to Find Out What’s Going On? • Take all the differences between N-SCAN and Twinscan and run them on both to compare the results • (Hopefully) discover that some additional information is coded in the conservation model that wasn’t there before • Eventually improve the conservation model

  4. What’s Different • UTR States (Randy/Sam) • PSC “Magic Constant” (Rachel/Randy) • MultiZ alignments (Bob/Randy) • CNC State (Bob/Randy) • Independence Assumptions (Randy) • The Model Itself (Randy) Could there be (gasp!) a bug?

  5. MultiZ Alignments • “Threaded Blockset Aligner” • Multiple alignments are usually done with a “reference sequence” -- not here • Constructed from pair BlastZ alignments • Reducing to Human-Mouse alignment should be nearly equivalent to pair BlastZ alignment

  6. Doesn’t Help • Blast • Multiz Gene Sensitivity 24.07% Gene Specificity 12.44% Transcript Sensitivity 21.32% Transcript Specificity 12.44% Exon Sensitivity 83.56% Exon Specificity 34.91% Nucleotide Sensitivity 89.83% Nucleotide Specificity 44.08% Gene Sensitivity 23.41% Gene Specificity 9.51% Transcript Sensitivity 20.74% Transcript Specificity 9.51% Exon Sensitivity 82.19% Exon Specificity 32.66% Nucleotide Sensitivity 88.72% Nucleotide Specificity 41.73%

  7. What’s the CNC State?

  8. What’s the CNC State? • In N-SCAN, prevents the 5’ UTR state from being entered too often • In theory, it should favor taking an OK-scoring CNC State over what should be a low-scoring CDS state visit. • Not really “trained” per se, just given the same conservation parameters as the 5’ UTR states

  9. So What? • This probably isn’t how N-Scan gets its boost. (Good.) • Perhaps the CNC state can be trained better. • More later….

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