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Title: Optimal screening designs for biomedical technology

Technical Report ·
DOI:https://doi.org/10.2172/532702· OSTI ID:532702

This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). Screening a large number of different types of molecules to isolate a few with desirable properties is essential in biomedical technology. For example, trying to find a particular gene in the Human genome could be akin to looking for a needle in a haystack. Fortunately, testing of mixtures, or pools, of molecules allows the desirable ones to be identified, using a number of experiments proportional only to the logarithm of the total number of experiments proportional only to the logarithm of the total number of types of molecules. We show how to capitalize upon this potential by using optimize pooling schemes, or designs. We propose efficient non-adaptive pooling designs, such as {open_quotes}random sets{close_quotes} designs and modified {open_quotes}row and column{close_quotes} designs. Our results have been applied in the pooling and unique-sequence screening of clone libraries used in the Human Genome Project and in the mapping of Human chromosome 16. This required the use of liquid-transferring robots and manifolds--for the largest clone libraries. Finally, we developed an efficient technique for finding the posterior probability each molecule has the desirable property, given the pool assay results. This technique works well, in practice, even if there are substantial rates of errors in the pool assay data. Both our methods and our results are relevant to a broad spectrum of research in modern biology.

Research Organization:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Assistant Secretary for Human Resources and Administration, Washington, DC (United States)
DOE Contract Number:
W-7405-ENG-36
OSTI ID:
532702
Report Number(s):
LA-UR-97-3500; ON: DE98000071; TRN: 97:005350
Resource Relation:
Other Information: PBD: [1997]
Country of Publication:
United States
Language:
English

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