S Kasif | PubMed Health

PubMed1998

Microbial gene identification using interpolated Markov models.

This paper describes a new system, GLIMMER, for finding genes in microbial genomes. In a series of tests on Haemophilus influenzae , Helicobacter pylori and other complete microbial genomes, this system has proven to be very accurate at locating virtually all the genes in these sequences, outperforming previous methods. A conservative estimate based on experiments on H.pylori and H. influenzae is that the system finds >97% of all genes. GLIMMER uses interpolated Markov models (IMMs) as a framework for capturing dependencies between nearby nucleotides in a DNA sequence. An IMM-based method makes predictions based on a variable context; i.e., a variable-length oligomer in a DNA sequence. The context used by GLIMMER changes depending on the local composition of the sequence. As a result, GLIMMER is more flexible and more powerful than fixed-order Markov methods, which have previously been the primary content-based technique for finding genes in microbial DNA.

Algorithms↗

PubMed1993

Protein secondary structure modelling with probabilistic networks.

In this paper we study the performance of probabilistic networks in the context of protein sequence analysis in molecular biology. Specifically, we report the results of our initial experiments applying this framework to the problem of protein secondary structure prediction. One of the main advantages of the probabilistic approach we describe here is our ability to perform detailed experiments where we can experiment with different models. We can easily perform local substitutions (mutations) and measure (probabilistically) their effect on the global structure. Window-based methods do not support such experimentation as readily. Our method is efficient both during training and during prediction, which is important in order to be able to perform many experiments with different networks. We believe that probabilistic methods are comparable to other methods in prediction quality. In addition, the predictions generated by our methods have precise quantitative semantics which is not shared by other classification methods. Specifically, all the causal and statistical independence assumptions are made explicit in our networks thereby allowing biologists to study and experiment with different causal models in a convenient manner.

Algorithms↗