this article were defrayed in part by payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact

this paper, we explicitly delineate the interdependencies among these parameters and explore the trade-o#s in parameter space: e.g., sizing error vs. digestion rate vs. total coverage. 1.1 Summary of the Main Results

This paper describes the underlying mathematical model and the dynamic programming algorithm technology for the validation of a (DNA) sequence against a (DNA) map. The sequence can be obtained from a variety of sources (e.g. GenBank, Sanger's Lab, or Celera P.E.) and it is assumed to be written out as a string of nucleotides. The map is an ordered restriction map obtained through an optical mapping process and is augmented with statistical information which will be used to place (or not) the sequence in the genome. Our approach has many other applications beyond validation: e.g. map-based sequence assembly, phasing sequence contigs, detecting and closing gaps and annotation of partially sequenced genomes to nd open reading frames, genes, and synteny groups. We tested our system by checking various maps against publicly available sequence data for Plasmodium falciparum (cf. [10, 11]). 1 Object Denitions and Processes Denitions The objects we will be dealing with in the following are...

Modern comparative genomics has been established, in part, by the sequencing and annotation of a broad range of microbial species. To gain further insights, new sequencing efforts are now dealing with the variety of strains or isolates that gives a species definition and range; however, this number vastly outstrips our ability to sequence them. Given the availability of a large number of microbial species, new whole genome approaches must be developed to fully leverage this information at the level of strain diversity that maximize discovery. Here, we describe how optical mapping, a single-molecule system, was used to identify and annotate chromosomal alterations between bacterial strains represented by several species. Since whole-genome optical maps are ordered restriction maps, sequenced strains of Shigella flexneri serotype 2a (2457T and 301), Yersinia pestis (CO 92 and KIM), and Escherichia coli were aligned as maps to identify regions of homology and to further characterize them as possible insertions, deletions, inversions, or translocations. Importantly, an unsequenced Shigella flexneri strain (serotype Y strain AMC[328Y]) was optically mapped and aligned with two sequenced ones to reveal one novel locus implicated in serotype conversion and several other loci containing insertion sequence elements or phage-related gene insertions. Our results suggest that genomic rearrangements and chromosomal breakpoints are readily identified and annotated against a prototypic sequenced strain by using the tools of optical mapping.

To my parents.

contigs; the resulting tool termed "ConVEx" (Contig Visualization and Exploration tool) has facilitated our mapping work on P.falciparum, D.radiodurans, E.coli and H.sapien. In these applications, Optical Mapping process was used to create partially-digested but ordered restriction maps from a large number of genomic DNA molecules---the fragments had up to 10% sizing error and occasionally contained optical cuts and optical chimerism. A statistical algorithm called Gentig (jointly developed with T.S. Anantharaman), by means of a powerful Bayesian inference, was able to contig these individual maps into multi-megabase islands quickly. For instance, a 0.6X coverage contigs for human DNA was assembled within few hours. The restriction maps of this size and complexity can be best understood when they are anchored to and interpreted in the context of all other available maps and sequence data in the same chromosomal region, organized in a multi-scale hierarchy. In order to face

This paper describes the underlying mathematical model and the dynamic programming algorithm technology for the validation of a (DNA) sequence against a (DNA) map. The sequence can be obtained from a variety of sources (e.g. GenBank, Sanger's Lab, or Celera P.E.) and it is assumed to be written out as a string of nucleotides. The map is an ordered restriction map obtained through an optical mapping process and is augmented with statistical information which will be used to place (or not) the sequence in the genome. Our approach has many other applications beyond validation: e.g. map-based sequence assembly, phasing sequence contigs, detecting and closing gaps and annotation of partially sequenced genomes to nd open reading frames, genes, and synteny groups. We tested our system by checking various maps against publicly available sequence data for Plasmodium falciparum (cf. [9, 10]). 1 Object Denitions and Processes Denitions The objects we will be dealing with in the following are ...

this paper; Saxena et al. 2000). The complexity of this locus has made the physical mapping of the DAZ region exceedingly difficult. The majority of STS markers derived from this locus are not single-copy, making the creation of clone contigs by PCR analysis virtually impossible

this paper (one 600-bp BamHI fragment is missing on the whole genome map). The success of this project has prompted the Malaria Genome Consortium to recommend support of whole genome mapping to assist in closure of chromosomes, as well as for verification of the final assembly

We collaborate in a research program aimed at creating a rigorous framework, experimental infrastructure, and computational environment for understanding, experimenting with, manipulating, and modifying a diverse set of fundamental biological processes at multiple scales and spatio-temporal modes. The novelty of our research is based on an approach that (i) requires coevolu- # The work reported in this paper was supported by grants from NSF's Qubic program, DARPA, HHMI biomedical support research grant, the US Department of Energy, the US Air Force, National Institutes of Health, and New York State O#ce of Science, Technology & Academic Research.