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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 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
Multiple ITS Copies Reveal Extensive Hybridization within Rheum (Polygonaceae), a Genus That Has Undergone Rapid Radiation
During adaptive radiation events, characters can arise multiple times due to parallel evolution, but transfer of traits through hybridization provides an alternative explanation for the same character appearing in apparently non-sister lineages. The signature of hybridization can be detected in incongruence between phylogenies derived from different markers, or from the presence of two divergent versions of a nuclear marker such as ITS within one individual.In this study, we cloned and sequenced ITS regions for 30 species of the genus Rheum, and compared them with a cpDNA phylogeny. Seven species contained two divergent copies of ITS that resolved in different clades from one another in each case, indicating hybridization events too recent for concerted evolution to have homogenised the ITS sequences. Hybridization was also indicated in at least two further species via incongruence in their position between ITS and cpDNA phylogenies. None of the ITS sequences present in these nine species matched those detected in any other species, which provides tentative evidence against recent introgression as an explanation. Rheum globulosum, previously indicated by cpDNA to represent an independent origin of decumbent habit, is indicated by ITS to be part of clade of decumbent species, which acquired cpDNA of another clade via hybridization. However decumbent and glasshouse morphology are confirmed to have arisen three and two times, respectively.These findings suggested that hybridization among QTP species of Rheum has been extensive, and that a role of hybridization in diversification of Rheum requires investigation
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