Whole-genome comparative annotation and regulatory motif discovery in multiple yeast species

ABSTRACT

In [13] we reported the genome sequences of S. paradoxus, S. mikatae and S. bayanus and compared these three yeast species to their close relative, S. cerevisiae. Genome-wide comparative analysis allowed the identification of functionally important sequences, both coding and non-coding. In this companion paper we describe the mathematical and algorithmic results underpinning the analysis of these genomes.We developed statistical methods for the systematic de-novo identification of regulatory motifs. Without making use of co-regulated gene sets, we discovered virtually all previously known DNA regulatory motifs as well as several noteworthy novel motifs. With the additional use of gene ontology information, expression clusters and transcription factor binding profiles, we assigned candidate functions to the novel motifs discovered.Our results demonstrate that entirely automatic genome-wide annotation, gene validation, and discovery of regulatory motifs is possible. Our findings are validated by the extensive experimental knowledge in yeast, confirming their applicability to other genomes.

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INDEX TERMS

Primary Classification:
  J. Computer Applications
  J.3 LIFE AND MEDICAL SCIENCES
      Subjects: Biology and genetics

General Terms:
Algorithms

Keywords:
comparative genomics, computational biology, genome annotation, regulatory motif discovery