Sensitivity, Specificity and the Hybridization Isotherms of DNA Chips

Competitve hybridization, at the surface and in the bulk, lowers the sensitivity of DNA chips. Competitive surface hybridization occurs when different targets can hybridize with the same probe. Competitive bulk hybridization takes place when the targets can hybridize with free complementary chains in the solution. The effects of competitive hybridization on the thermodynamically attainable performance of DNA chips are quantified in terms of the hybridization isotherms of the spots. These relate the equilibrium degree of the hybridization to the bulk composition. The hybridization isotherm emerges as a Langmuir isotherm modified for electrostatic interactions within the probe layer. The sensitivity of the assay in equilibrium is directly related to the slope of the isotherm. A simpler description is possible in terms of $c_{50}$s specifying the bulk composition corresponding to 50% hybridization at the surface. The effects of competitive hybridization are important for the quantitative analysis of DNA chip results especially when used to study point mutations.Comment: 18 pages and 7 figures. To be published in Biophys.

On Limits of Performance of DNA Microarrays

DNA microarray technology relies on the hybridization process which is stochastic in nature. Probabilistic cross-hybridization of non-specific targets, as well as the shot-noise originating from specific targets binding, are among the many obstacles for achieving high accuracy in DNA microarray analysis. In this paper, we use statistical model of hybridization and cross-hybridization processes to derive a lower bound (viz., the Cramer-Rao bound) on the minimum mean-square error of the target concentrations estimation. A preliminary study of the Cramer-Rao bound for estimating the target concentrations suggests that, in some regimes, cross-hybridization may, in fact, be beneficial—a result with potential ramifications for probe design, which is currently focused on minimizing cross-hybridization

Competing Orderings in an Extended Falicov-Kimball Model

We present a Hartree-Fock study of the Falicov-Kimball model extended by both on-site and non-local hybridization. We examine the interplay between excitonic effects and the charge-density wave (CDW) instability known to exist at zero hybridization. It is found that the CDW state remains stable in the presence of finite hybridization; for on-site hybridization the Coulomb interaction nevertheless strongly enhances the excitonic average above its value in the noninteracting system. In contrast, for non-local hybridization, we observe no such enhancement of the excitonic average or a spontaneous on-site hybridization potential. Instead, we find only a significant suppression of the excitonic correlations in the CDW state. A phenomenological Ginzburg-Landau analysis is also provided to understand the interplay.Comment: RevTex, 5 pages, 4 figures; expanded and corrected, typos added, references adde

Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNAs with radioactive and non-radioactive in situ hybridization techniques: diagnosis of trisomy 18 with probe L1.84

The localization of chromosome 18 in human interphase nuclei is demonstrated by use of radioactive and nonradioactive in situ hybridization techniques with a DNA clone designated L1.84. This clone represents a distinct subpopulation of the repetitive human alphoid DNA family, located in the centric region of chromosome 18. Under stringent hybridization conditions hybridization of L1.84 is restricted to chromosome 18 and reflects the number of these chromosomes present in the nuclei, namely, two in normal diploid human cells and three in nuclei from cells with trisomy 18. Under conditions of low stringency, cross-hybridization with other subpopulations of the alphoid DNA family occurs in the centromeric regions of the whole chromosome complement, and numerous hybridization sites are detected over interphase nuclei. Detection of chromosome-specific target DNAs by non-radioactive in situ hybridization with appropriate DNA probes cloned from individual chromosomal subregions presents a rapid means of identifying directly numerical or even structural chromosome aberrations in the interphase nucleus. Present limitations and future applications of interphase cytogenetics are discussed

Modeling the kinetics of hybridization in microarrays

Conventional fluorescent-based microarrays acquire data after the hybridization phase. In this phase the targets analytes (i.e., DNA fragments) bind to the capturing probes on the array and supposedly reach a steady state. Accordingly, microarray experiments essentially provide only a single, steady-state data point of the hybridization process. On the other hand, a novel technique (i.e., realtime microarrays) capable of recording the kinetics of hybridization in fluorescent-based microarrays has recently been proposed in [5]. The richness of the information obtained therein promises higher signal-to-noise ratio, smaller estimation error, and broader assay detection dynamic range compared to the conventional microarrays. In the current paper, we develop a probabilistic model of the kinetics of hybridization and describe a procedure for the estimation of its parameters which include the binding rate and target concentration. This probabilistic model is an important step towards developing optimal detection algorithms for the microarrays which measure the kinetics of hybridization, and to understanding their fundamental limitations

Slave boson theory of the extended Falicov-Kimball model

The extended Falicov-Kimball model, with both an on-site hybridization potential and dispersive narrow band, is examined within the saddle-point approximation to the Kotliar-Ruckenstein slave boson theory. We first set the hybridization potential to zero and find that the phase diagram depends strongly upon the orbital structure: for degenerate orbitals, a correlated-insulating state is found at sufficiently strong interaction strengths, whereas a finite orbital energy difference can lead to discontinuous valence transitions. The obtained phase diagram is very sensitive to the presence of a finite hybridization potential. As in Hartree-Fock theory, we find an enhancement of the hybridization by the inter-orbital Coulomb repulsion. The more precise treatment of correlation effects, however, leads to large deviations from the Hartree-Fock results. In the limit of vanishing hybridization an excitonic insulator state is only found when the orbitals are degenerate, which restricts this phase to a much smaller parameter space than in other available mean-field theories.Comment: 23 pages, 10 figure