A branch-and-cut approach to physical mapping with end-probes
- Universitaet Heidelberg (Germany)
- Universitaet zu Koeln (Germany); and others
A fundamental problem in computational biology is the construction of physical maps of chromosomes from hybridization experiments between unique probes and clones of chromosome fragments in the presence of error. Alizadeh, Karp, Weisser and Zweig [AKWZ94] first considered a maximum-likelihood model of the problem that is equivalent to finding an ordering of the probes that minimizes a weighted sum of errors, and developed several effective heuristics. We show that by exploiting information about the end-probes of clones, this model can be formulated as a weighted Betweenness Problem. This affords the significant advantage of allowing the well-developed tools of integer linear-programming and branch-and-cut algorithms to be brought to bear on physical mapping, enabling us for the first time to solve small mapping instances to optimality even in the presence of high error. We also show that by combining the optimal solution of many small overlapping Betweenness Problems, one can effectively screen errors from larger instances, and solve the edited instance to optimality as a Hamming-Distance Traveling Salesman Problem. This suggests a new combined approach to physical map construction. 18 refs., 13 figs.
- Research Organization:
- Association for Computing Machinery, New York, NY (United States); Sloan (Alfred P.) Foundation, New York, NY (United States)
- OSTI ID:
- 548999
- Report Number(s):
- CONF-970137-; TRN: 97:005298-0011
- Resource Relation:
- Conference: RECOMB `97: 1. annual conference on research in computational molecular biology, Santa Fe, NM (United States), 20-22 Jan 1997; Other Information: PBD: 1997; Related Information: Is Part Of RECOMB 97. Proceedings of the first annual international conference on computational molecular biology; PB: 370 p.
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
99 MATHEMATICS
COMPUTERS
INFORMATION SCIENCE
MANAGEMENT
LAW
MISCELLANEOUS
HUMAN CHROMOSOMES
DNA HYBRIDIZATION
GENETIC MAPPING
CHROMOSOME BREAKAGE
DNA-CLONING
CHIMERAS
ALGORITHMS
ERRORS
LINEAR PROGRAMMING
MAXIMUM-LIKELIHOOD FIT
MATHEMATICAL MODELS
MOLECULAR BIOLOGY
PROBES