The overall objective of this research has been and continues to be the development of computer techniques for constructing high-resolution restriction maps, pushing the boundary of automated construction as far as possible. In this phase of the activity, the focus will turn to: (a) whole-chromosome mapping at the cosmid level, eliminating a dependence on prior mapping of the chromosome at the YAC level, and (b) the transfer of Multile-Complete-Digestion (MCD) high-resolution restriction-fragment mapping techniques to creating sequence-ready maps. These activities are in direct support of: (i) decreasing the human-intensive component required for mapping and sequencing, (ii) increasing the quality and continuity of the maps and sequences produced, and (iii) reducing the overall time and cost of mapping and sequencing. Computer techniques that we have already developed to produce restriction maps of YACs with cosmid clones will be refined to address whole- chromosome mapping with cosmids and enhanced to producing sequence-ready maps of small-insert clones, such as M13 and plasmids. We plan to allow synchronizing the sequence-ready maps with the """"""""parent"""""""" maps composed of cosmids, using tie-point landmarks common to both.
Our specific aims are to: 1) Upgrade our current mapping techniques to produce a system capable of perform whole-chromosome mapping at the cosmid level. The primary mapping technique for achieving this will be the construction of a new bridging MCD approach. 2) Transfer the high-resolution restriction-mapping technology that has been developed to the construction of sequence-ready maps of at the small-insert clone level. This transfer will include enhancements of the basic MCD mapping technique to take advantage of forms of data other than complete- restriction-fragment data, such as sequence data and end-labeled-fragment data. 3) Enhance supporting techniques to push automated mapping as far as possible. This will include the development and integration of a number of independent techniques which are currently done by human-intensive activities. 4) Convert the system to a true object-oriented paradigm so that its components are modifiable, extendible, and embeddable in production environments. This will be achieved by converting the present functionality to C++, refurbishing the code during the conversion.
| Gillett, W; Hanks, L; Wong, G K et al. (1996) Assembly of high-resolution restriction maps based on multiple complete digests of a redundant set of overlapping clones. Genomics 33:389-408 |
| Gillett, W; Daues, J; Hanks, L et al. (1995) Fragment collapsing and splitting while assembling high-resolution restriction maps. J Comput Biol 2:185-205 |
