dorsal/arxiv
View SchemaDNA hybridization to mismatched templates: a chip study
| Authors | Felix Naef, Daniel A. Lim, Nila Patil, Marcelo Magnasco |
|---|---|
| Categories | |
| ArXiv ID | physics/0111199 |
| URL | https://arxiv.org/abs/physics/0111199 |
| DOI | 10.1103/PhysRevE.65.040902 |
Abstract
High-density oligonucleotide arrays are among the most rapidly expanding technologies in biology today. In the {\sl GeneChip} system, the reconstruction of the target concentration depends upon the differential signal generated from hybridizing the target RNA to two nearly identical templates: a perfect match (PM) and a single mismatch (MM) probe. It has been observed that a large fraction of MM probes repeatably bind targets better than the PMs, against the usual expectation from sequence-specific hybridization; this is difficult to interpret in terms of the underlying physics. We examine this problem via a statistical analysis of a large set of microarray experiments. We classify the probes according to their signal to noise ($S/N$) ratio, defined as the eccentricity of a (PM, MM) pair's `trajectory' across many experiments. Of those probes having large $S/N$ ($>3$) only a fraction behave consistently with the commonly assumed hybridization model. Our results imply that the physics of DNA hybridization in microarrays is more complex than expected, and they suggest new ways of constructing estimators for the target RNA concentration.
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"abstract": "High-density oligonucleotide arrays are among the most rapidly expanding\ntechnologies in biology today. In the {\\sl GeneChip} system, the reconstruction\nof the target concentration depends upon the differential signal generated from\nhybridizing the target RNA to two nearly identical templates: a perfect match\n(PM) and a single mismatch (MM) probe. It has been observed that a large\nfraction of MM probes repeatably bind targets better than the PMs, against the\nusual expectation from sequence-specific hybridization; this is difficult to\ninterpret in terms of the underlying physics. We examine this problem via a\nstatistical analysis of a large set of microarray experiments. We classify the\nprobes according to their signal to noise ($S/N$) ratio, defined as the\neccentricity of a (PM, MM) pair\u0027s `trajectory\u0027 across many experiments. Of\nthose probes having large $S/N$ ($\u003e3$) only a fraction behave consistently with\nthe commonly assumed hybridization model. Our results imply that the physics of\nDNA hybridization in microarrays is more complex than expected, and they\nsuggest new ways of constructing estimators for the target RNA concentration.",
"arxiv_id": "physics/0111199",
"authors": [
"Felix Naef",
"Daniel A. Lim",
"Nila Patil",
"Marcelo Magnasco"
],
"categories": [
"physics.bio-ph",
"physics.data-an",
"q-bio"
],
"doi": "10.1103/PhysRevE.65.040902",
"title": "DNA hybridization to mismatched templates: a chip study",
"url": "https://arxiv.org/abs/physics/0111199"
},
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