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Biomedical subjects

David C Torney

Publications and source records attributed to David C Torney.

3 recordsLinked to original sources

New t-gap insertion-deletion-like metrics for DNA hybridization thermodynamic modeling.

We discuss the concept of t-gap block isomorphic subsequences and use it to describe new abstract string metrics that are similar to the Levenshtein insertion-deletion metric. Some of the metrics that we define can be used to model a thermodynamic distance function on single-stranded DNA sequences. Our model captures a key aspect of the nearest neighbor thermodynamic model for hybridized DNA duplexes. One version of our metric gives the maximum number of stacked pairs of hydrogen bonded nucleotide base pairs that can be present in any secondary structure in a hybridized DNA duplex without pseudoknots. Thermodynamic distance functions are important components in the construction of DNA codes, and DNA codes are important components in biomolecular computing, nanotechnology, and other biotechnical applications that employ DNA hybridization assays. We show how our new distances can be calculated by using a dynamic programming method, and we derive a Varshamov-Gilbert-like lower bound on the size of some of codes using these distance functions as constraints. We also discuss software implementation of our DNA code design methods.

Base Sequence↗

The sequence and analysis of duplication-rich human chromosome 16.

Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.

Animals↗

Group testing with DNA chips: generating designs and decoding experiments.

DNA microarrays are a valuable tool for massively parallel DNA-DNA hybridization experiments. Currently, most applications rely on the existence of sequence-specific oligonucleotide probes. In large families of closely related target sequences, such as different virus subtypes, the high degree of similarity often makes it impossible to find a unique probe for every target. Fortunately, this is unnecessary. We propose a microarray design methodology based on a group testing approach. While probes might bind to multiple targets simultaneously, a properly chosen probe set can still unambiguously distinguish the presence of one target set from the presence of a different target set. Our method is the first one that explicitly takes cross-hybridization and experimental errors into account while accommodating several targets. The approach consists of three steps: (1) Pre-selection of probe candidates, (2) Generation of a suitable group testing design, and (3) Decoding of hybridization results to infer presence or absence of individual targets. Our results show that this approach is very promising, even for challenging data sets and experimental error rates of up to 5%. On a data set of 28S rDNA sequences we were able to identify 660 sequences, a substantial improvement over a prior approach using unique probes which only identified 408 sequences.

Algorithms↗