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Enhancing Gene Prediction with Conservation Score Coefficient (CSC) in ISCAN

Investigating the impact of Conservation Score Coefficient (CSC) on gene prediction accuracy in ISCAN. Learn how CSC combines target DNA and conservation sequences to improve predictions. Discover results, modifications required for ISCAN, and comparison with NSCAN.

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Enhancing Gene Prediction with Conservation Score Coefficient (CSC) in ISCAN

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  1. Conservation Score Coefficient (CSC) Does the choice of CSC improve gene prediction in ISCAN? Rachel Pusey 27 July 2005

  2. Value added prediction Conservation sequence Mouse:••││-││-•• ISCAN Prediction Target DNA sequence Human: TATTCAG Informant sequence(s) Mouse: GGACGTG Chicken:GTACGAG NSCAN

  3. What is the CSC? In the midst of the Viterbi algorithm: • log likelihood used to decide the most likely state for this base/position • normally just for the DNA target sequence • in NSCAN/ISCAN also have the informant/conservation sequence(s) • combine the two log likelihoods: just add them together

  4. What is the CSC? ISCAN log(Ts(i)/Tnull(i)) + CSC • log(Cs(i)/Cnull(i)) T : target DNA C : conservation CSC : conservation sequence constant NSCAN log(Ts(i)/Tnull(i)) + PSC • log(Is(i)/Inull(i)) T : target DNA I : informant PSC : phylogenetic sequence constant

  5. NSCAN results • Results already calculated for NSCAN, showing how prediction accuracy varied with PSC. • Noticable improvement for values ~0.4 i.e. less influence for the informants. Ref: Using Multiple Alignments to Improve Gene PredictionSamuel S. Grossand Michael R. Brent

  6. NSCAN results

  7. NSCAN results

  8. What about ISCAN? • Alter current version of ISCAN/zoe code • only need to change half a dozen lines • (CVS not updated) • Run on the human genome • parameter source • /bio/pkg/parameter/human/human_iscan_utr.zhmm • DNA source • /bio/pro/Homo_sapiens/assembly/hg17/chr_split/<chr#>/fragment_<frag#>/<frag#>.seq.masked

  9. The usual pipeline • Run modified ISCAN on 1MB fragments → gtf output • Run unsplit_twinscan_gtf.pl to glue the fragments back together • Run evaluate_gtf.pl on individual chromosomes, also on aggregate lists • source for gtf for evaluation • /bio/db/Homo_sapiens/assembly/hg17/annotation/refseqs_v2/chr<chr#>.eval.gtf

  10. ISCAN results

  11. ISCAN results

  12. ISCAN results

  13. ISCAN results

  14. NSCAN vs. ISCAN

  15. NSCAN vs. ISCAN

  16. Summary • Less pronounced effect for CSC than PSC • Peak around 0.6-0.7 • Considerable variation between chromosomes e.g. • chr1 similar to aggregate, smooth curve • chr13, chrY flat with noise

  17. Conclusion? • Haven't been missing out on the panacea for all ills – or at least this isn't it.

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