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Biomedical subjects

C N Yee

Publications and source records attributed to C N Yee.

6 recordsLinked to original sources

A restriction mapping engine using constraint logic programming.

Restriction mapping generally requires the application of information from various digestions by restriction enzymes to find solution sets. We use both the predicate calculus and constraint solving capabilities of CLP(R) to develop an engine for restriction mapping. Many of the techniques employed by biologists to manually find solutions are supported by the engine in a consistent manner. We provide generalized pipeline and cross-multiply operators for combining sub-maps. Our approach encourages the building of maps iteratively. We show how other techniques can be readily incorporated.

Animals

Finite-state models in the alignment of macromolecules.

Minimum message length encoding is a technique of inductive inference with theoretical and practical advantages. It allows the posterior odds-ratio of two theories or hypotheses to be calculated. Here it is applied to problems of aligning or relating two strings, in particular two biological macromolecules. We compare the r-theory, that the strings are related, with the null-theory, that they are not related. If they are related, the probabilities of the various alignments can be calculated. This is done for one-, three-, and five-state models of relation or mutation. These correspond to linear and piecewise linear cost functions on runs of insertions and deletions. We describe how to estimate parameters of a model. The validity of a model is itself an hypothesis and can be objectively tested. This is done on real DNA strings and on artificial data. The tests on artificial data indicate limits on what can be inferred in various situations. The tests on real DNA support either the three- or five-state models over the one-state model. Finally, a fast, approximate minimum message length string comparison algorithm is described.

Algorithms

Minimum message length encoding and the comparison of macromolecules.

A comparison of inductive inference known as minimum message length encoding is applied to string comparison in molecular biology. The question of whether or not two strings are related and, if so, of how they are related and the problem of finding a good theory of string mutation are treated as inductive inference problems. The method allows the posterior odds-ratio of two string alignments or of two models of string mutation to be computed. The connection between models of mutation and existing string alignment algorithms is made explicit. A fast minimum message length alignment algorithm is also described.

Base Sequence

Restriction site mapping for three or more enzymes.

Restriction site mapping requires a generator to put forward possible maps and a constraint checker to reject false maps. Ideally these combine to give an algorithm which calculates a sound and complete solution set. Three algorithms for generation are presented and compared. Two decompose a multi-enzyme problem (greater than or equal to 3) into subproblems. The constraint checker is based on separation theory. Some insights into the extent of constraint checking involved in and feasibility of more checking for three or more enzymes are discussed. The trade-off between computation time and the soundness of the solution set is examined.

Algorithms

Restriction site mapping is in separation theory.

A computer algorithm for restriction-site mapping consists of a generator of partial maps and a consistency checker. This paper examines consistency checking and argues that a method based on separation theory extracts the maximum amount of information from fragment lengths in digest data. It results in the minimum number of false maps being generated.

Algorithms