Nucleic acids, arrays

The manufacture and processing of the protein microarray should be conducted in such a manner that the arrayed proteins remain in their native and active state. For most proteins, this usually means the hydrated state in order to avoid surface denaturation. For antibody arrays which are perhaps more forgiving than other proteins, it has been our experience that while these could be stored cold and dry, it is most important to rehydrate them prior to use. This process is in sharp contrast to the preparation of nucleic acid arrays in which strand melting or denaturahon is necessary to achieve optimal binding to the solid support. While the hybridization process is well understood and can be controlled under thermodynamic principles, the folding and renaturation of proteins on planar (microarray) surfaces is under study. 

Nucleic acid arrays are used in the research labs at F. Hoffmann-La Roche in two varieties. One is represented by the commercially available high-density oUgonn-cleotide arrays in which the samples are synthesized in situ and covalently bonnd to the substrate (Affymetrix ). The other is the so-called custom spotted arrays in which the droplets that contain different molecules are deposited on the substrate. If the nucleic acid sequence is known, but not available on a commercial chip, oligonucleotides are synthesized and deposited, hi cases for which the sequence is not known, microarrays of cDNA fragments or plasmids are used. 

ANALYSIS OF GENE EXPRESSION PATTERNS USING NUCLEIC ACID ARRAYS... 

The methodological advances just presented have brought the field of nucleic acid force field calculations to a point where results from the calculations can be used with reasonable confidence to aid in the interpretation of experimental data as well as to be used for scientific investigations that are not accessible to experiment. Accordingly, a number of studies based on MD simulations, as well as other methods, have been undertaken to study a wide array of biologically relevant events associated with DNA. A brief overview of some of these efforts follows. 

Thompson KL et al (2005) Use of a mixed tissue RNA design for performance assessments on multiple micro-array formats. Nucleic Acids Res 33 el 87... 

A microscopic, ordered array of nucleic acids, proteins, small molecules, cells or other substances that enables parallel analysis of complex biochemical samples. 

Microarray hybridization is a process by which nucleic acids are detected by hybridizing with complementary sequences bound to wafers at specific array coordinates. Hundreds to thousands of gene products may be measured in a single experiment. 

Some virus particles have their protein subunits symmetrically packed in a helical array, forming hollow cylinders. The tobacco mosaic virus (TMV) is the classic example. X-ray diffraction data and electron micrographs have revealed that 16 subunits per turn of the helix project from a central axial hole that runs the length of the particle. The nucleic acid does not lie in this hole, but is embedded into ridges on the inside of each subunit and describes its own helix from one end of the particle to the other. 

The development of DNA sensors and high-density DNA arrays has been prompted by the tremendous demands for innovative analytical tools capable of delivering the genetic information in a faster, simpler, and cheaper manner at the sample source, compared to traditional nucleic acid assays. Nanoparticle-biopolymer conjugates offer great potential for DNA diagnostics and can have a profound impact upon bioanalytical chemistry. Nanoparticle/polynucleotide assemblies for advanced electrical detection of DNA sequences have been reviewed by Wang [145]. 

Shi Y., Simpson P.C., Scherer J.R., Wexler D., Skibola C., Smith, M.T., and Mathies R.A., Radial capillary array electrophoresis microplate and scanner for high-performance nucleic acid analysis, Anal. Chem. 71, 5354, 1999. 

The compounds that are identifiable in the sea represent a vast array of biochemicals attributable to the life and death of marine plants and animals. They are generally grouped into six classes based on structural similarities hydrocarbons, carbohydrates, lipids, fatty acids, amino acids, and nucleic acids. Because they represent compounds that can be quantified and understood for their chemical properties and known role in biological systems, a great deal of information has been accumulated over the years about these groups and the specific compounds found within them.7... 

The difficulty with protein arrays is that proteins do not behave as uniformly as nucleic acid. Protein function is dependent on a precise, and fragile, three-dimensional structure that may be difficult to maintain in an array format. In addition, the strength and stability of interactions between proteins are not nearly as standardized as nucleic acid hybridization. Each protein-protein interaction is unique and could assume a wide range of affinities. Currently, protein expression mapping is performed almost exclusively by two-dimensional electrophoresis and mass spectrometry. The development of protein arrays, however, could provide another powerful... 

Second is the application of a wide range of experimental designs and techniques. DNA CT is observed in a diverse array of systems over different distance and time regimes. Consequently, a versatile approach which draws upon complementary methods is required to explore different facets of this chemistry and develop a complete picture. We interrogate a variety of nucleic acid assemblies using spectroscopic, biochemical and electrochemical tools to define mechanistic features, exploit biological applications, and explore biological consequences of DNA CT. 

Ylstra B, Van den IJssel P, Carvalho B, et al. BAC to the future or oligonucleotides a perspective for micro array comparative genomic hybridization (array CGH). Nucleic Acids Res. 2006 34 445 150. 

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