Open AccessJournal Article10.1002/CHIN.200406230

ChipCheck — A Program Predicting Total Hybridization Equilibria for DNA Binding to Small Oligonucleotide Microarrays.

- 10 Feb 2004

- Vol. 35, Iss: 6

TL;DR: Chip as mentioned in this paper is a program that allows the computation of total hybridization equilibria for hybridization experiments involving small oligonucleotide arrays, which requires the free energies of binding for all pairs of probes and targets as well as total strand concentrations and probe molecule numbers.

Abstract: Presented here is the program ChipCheck that allows the computation of total hybridization equilibria for hybridization experiments involving small oligonucleotide arrays. The calculation requires the free energies of binding for all pairs of probes and targets as well as total strand concentrations and probe molecule numbers. ChipCheck has been tested computationally on microarrays with up to 100 spots and 42 target strands (4200 binding equilibria). It arrives at solutions through iterations employing the multidimensional Newton method. While currently running in simulation mode only, an extension of the approach to the exhaustive analysis of chip results is being outlined and may be implemented in the future. The output displays the extent of correct and cross hybridization both graphically and numerically. In principle, calculating total hybridization equilibria allows for eliminating noise from DNA chip results and thus an improvement in sensitivity and accuracy.

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1. What contributions have the authors mentioned in the paper "Chipchecksa program predicting total hybridization equilibria for dna binding to small oligonucleotide microarrays" ?

ChipCheck this paper uses the multidimensional Newton method to compute the bounding energies of all pairs of probes and targets as well as total strand concentrations and probe molecule numbers.

Figure 5. Screenshot of an output of a total hybridization calculation performed onExample 2. Total hybridizations per spot are shown with low level binding by cross-hybridizing strands highlighted in red. Mismatched nucleotides in probe sequences were entered as lower case letters, solely to highlight their position.

Figure 1. Cartoon of a hybridization on a DNA chip producing both correct and false signals.

Figure 6. Screenshot of the ChipCheck output of a total hybridization calculation onExample 3featuring 100 probe spots and 42 target strands. To improve the readability, the numerical information representing the extent of spot coverage was omitted. The full data set, with better readability, can be created on the ChipCheck Internet page using theExample 3file.

Figure 7. Comparison of experimental (a) and simulated (b) hybridization results with the sequences 5′-TAGTTGACTGCGAT3′ (MM), 5′-chl-TGGTTGACTGCGAT-3′(chl-PM), and 5′-TGGTTGACTGCGAT-3′ (PM) as immobilized probes and 5′-Cy3ATCGCAGTCAACCA-3′ as target. The integration area of the fluorescence values reported in Figure 2 of ref 40 are plotted in (a), whereas (b) shows the relative fluorescence intensities expected based on the ChipCheck simulation. See ref 40 for experimental details.

Figure 2. Compilation of terms and equations employed in this work.

Figure 4. Screenshots of ChipCheck outputs of calculations on Example 1showing total hybridizations per spot (a) with equimolar amounts of the target strands and (b) with target strands 4 and 5 depleted by 3 orders of magnitude.

Citations

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References

•Journal Article•10.1021/CI034049A