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2005

Genetics

Articles 1 - 4 of 4

Full-Text Articles in Biomedical Engineering and Bioengineering

Genome-Wide Requirements For Resistance To Functionally Distinct Dna-Damaging Agents, Patrick Flaherty Jul 2005

Genome-Wide Requirements For Resistance To Functionally Distinct Dna-Damaging Agents, Patrick Flaherty

Patrick Flaherty

The mechanistic and therapeutic differences in the cellular response to DNA-damaging compounds are not completely understood, despite intense study. To expand our knowledge of DNA damage, we assayed the effects of 12 closely related DNA-damaging agents on the complete pool of ;4,700 barcoded homozygous deletion strains of
Saccharomyces cerevisiae. In our protocol, deletion strains are pooled together and grown competitively in the presence of compound. Relative strain sensitivity is determined by hybridization of PCR-amplified barcodes to an oligonucleotide array carrying the barcode complements. These screens identified genes in well-characterized DNAdamage-response pathways as well as genes whose role in the …

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A Latent Variable Model For Chemogenomic Profiling, Patrick Flaherty Jul 2005

A Latent Variable Model For Chemogenomic Profiling, Patrick Flaherty

Patrick Flaherty

Motivation: In haploinsufficiency profiling data, pleiotropic genes
are often misclassified by clustering algorithms that impose the constraint that a gene or experiment belong to only one cluster. We
have developed a general probabilistic model that clusters genes and
experiments without requiring that a given gene or drug only appear
in one cluster. The model also incorporates the functional annotation
of known genes to guide the clustering procedure.
Results: We applied our model to the clustering of 79 chemogenomic
experiments in yeast. Known pleiotropic genes PDR5 and MAL11 are
more accurately represented by the model than by a clustering procedure that …

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Genome-Wide Requirements For Resistance To Functionally Distinct Dna-Damaging Agents, Patrick Flaherty Jan 2005

Genome-Wide Requirements For Resistance To Functionally Distinct Dna-Damaging Agents, Patrick Flaherty

Mathematics and Statistics Department Faculty Publication Series

The mechanistic and therapeutic differences in the cellular response to DNA-damaging compounds are not completely understood, despite intense study. To expand our knowledge of DNA damage, we assayed the effects of 12 closely related DNA-damaging agents on the complete pool of ;4,700 barcoded homozygous deletion strains of Saccharomyces cerevisiae. In our protocol, deletion strains are pooled together and grown competitively in the presence of compound. Relative strain sensitivity is determined by hybridization of PCR-amplified barcodes to an oligonucleotide array carrying the barcode complements. These screens identified genes in well-characterized DNAdamage-response pathways as well as genes whose role in the DNA-damage …

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A Latent Variable Model For Chemogenomic Profiling, Patrick Flaherty Jan 2005

A Latent Variable Model For Chemogenomic Profiling, Patrick Flaherty

Mathematics and Statistics Department Faculty Publication Series

Motivation: In haploinsufficiency profiling data, pleiotropic genes are often misclassified by clustering algorithms that impose the constraint that a gene or experiment belong to only one cluster. We have developed a general probabilistic model that clusters genes and experiments without requiring that a given gene or drug only appear in one cluster. The model also incorporates the functional annotation of known genes to guide the clustering procedure. Results: We applied our model to the clustering of 79 chemogenomic experiments in yeast. Known pleiotropic genes PDR5 and MAL11 are more accurately represented by the model than by a clustering procedure that …

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