Comparative Annotation of Viral Genomes with Non-Conserved Gene Structure

1
Comparative Annotation of Viral Genomes with
Non-Conserved Gene Structure
Saskia de Groot and Jotun Hein Department of
Statistics, University of Oxford

• Motivation
• Viral genome annotation is a complex task
• Overlapping and nested reading frames
• Atypical sequence evolution
• Non-conserved gene structure

Results HIV2 vs. HIV2 84-89 Sensitivity
97-99.9 Specificity HIV1 vs.
HIV2 84 Sensitivity 98.5
Specificity HIV1 HIV2 98.7
Sensitivity 99.5 Specificity
? Current comparative HMM methodologies cant
cope.

• Aim
• Introduce a pair hidden Markov model to annotate
  two aligned homologous genomes simultaneously
• Analyse HIV1 and HIV2 two sequences related,
  but with non-homologous gene structure
• Incorporate prior knowledge by annotating one
  sequence conditional on the other

Methods Introduce pair HMM specific to
overlapping reading frames. 3 reading frames
? 23 x23 64 states Define three different
types of start transition probability a, ß,
? depending on coding state Use evolutionary
model specific to overlapping reading frames
substitutions are accepted by a selection
factor f. Use EM with Forward-Backward and
Newton-Raphson for parameter estimation
Viterbi to get annotation.

• Conclusion
• Shown validity of overlapping pair HMM approach
• Demonstrated amount of information contained in
  conservation of gene structure
• Provided successful method for annotating new
  viral strains

• Future Work
• Improve model by adding varying selection levels
• Incorporate a viral genome aligner for de novo
  gene annotation
• Build viral genome evolution simulator to test
  hypotheses