Using gene therapy to produce systemic levels of human factor IX for the treatment of hemophilia B has been clinically evaluated using viral-based vectors. The efficacy of this approach has been limited because of immune responses against the viral components. An alternative approach is to ...
Non-viral gene transfer into skeletal muscle in vivo is enhanced by electroporation (EP) to efficiencies far beyond any other (non-EP) method reported to date. Electroporation consistently delivers high levels of transgene to muscle and has been used extensively for the delivery of the ...
Here, we present a novel computational method, and related software, to synthesize signal transduction networks from single and double causal evidences. This is a significant and topical problem because there are currently no high-throughput experimental methods for construct ...
A genetic algorithm (GA) is a procedure that mimics processes occurring in Darwinian evolution to solve computational problems. A GA introduces variation through “mutation” and “recombination” in a “population” of possible solutions to a problem, encoded as strings of characters in “g ...
Several sequencing technologies have been introduced in recent years that dramatically outperform the traditional Sanger technology in terms of throughput and cost. The data generated by these technologies are characterized by generally shorter read lengths (as low as 35 bp) and dif ...
We give an overview of RNA structure predictions in this chapter. We discuss here the main approaches to RNA structure prediction: combinatorial approaches, comparative approaches, and kinetic approaches. The main algorithms and mathematical concepts such as transformational ...
Here, we describe transmembrane topology and signal peptide predictors and highlight their advantages and shortcomings. We also discuss the relation between these two types of prediction.
Expression microarrays are designed to quantify the amount of mRNA in a specific sample. However, this can only be done indirectly through quantifying the color intensities returned by labeled mRNA molecules bound to the array surface. Translating pixel intensities into transcript e ...
The tertiary structure of proteins can reveal information that is hard to detect in a linear sequence. Knowing the tertiary structure is valuable when generating hypothesis and interpreting data. Unfortunately, the gap between the number of known protein sequences and their associat ...
Functional characterization of a protein is often facilitated by its 3D structure. However, the fraction of experimentally known 3D models is currently less than 1% due to the inherently time-consuming and complicated nature of structure determination techniques. Computational ...
The main drawback of protein NMR spectroscopy today is still the extensive amount of time required for solving a single structure. The main bottleneck in this respect is the manual evaluation of the experimental spectra. A clear solution to this challenge is the development of automated metho ...
Protein crystallography emerged in the early 1970s and is, to this day, one of the most powerful techniques for the analysis of enzyme mechanisms and macromolecular interactions at the atomic level. It is also an extremely powerful tool for drug design. This field has evolved together with devel ...
Single-particle reconstruction is a methodology whereby transmission electron microscopy (TEM) is used to record images of individual monodisperse molecules or macromolecular assemblies, then sets of images of individual particles are computationally combined to prod ...
To support and guide an extensive experimental research into systems biology of signaling pathways, increasingly more mechanistic models are being developed with hopes of gaining further insight into biological processes. In order to analyze these models, computational and sta ...
The objective of the project reported in the present chapter was the reverse engineering of gene regulatory networks related to quorum sensing in the plant pathogen Pectobacterium atrosepticum from micorarray gene expression profiles, obtained from the wild-type and eight knocko ...
The nuclear pore complex (NPC) is the sole mediator of transport between the nucleus and the cytoplasm. The NPC is composed of about 30 distinct proteins, termed nucleoporins or nups. The yeast (Rout et al., J Cell Biol 148:635–651, 2000) and mammalian (Cronshaw et al., J Cell Biol 158:915–927, 2002) NPC have b ...
The complexity of proteomes makes good experimental design essential for their successful investigation. Here, we describe how proteomics experiments can be modeled and how computer simulations of these models can be used to improve experimental designs.
Mass spectrometry is a method of choice for quantifying low-abundance proteins and peptides in many biological studies. Here, we describe a range of computational aspects of protein and peptide quantitation, including methods for finding and integrating mass spectrometric pepti ...
A major challenge in proteomics is to fully identify and characterize posttranslational modification (PTM) patterns present at any given time in cells, tissues, and organisms. Currently, the most frequently used method for identifying PTMs is tandem mass spectrometry combined with ...
Protein identification by mass spectrometry is widely used in biological research. Here, we describe how the global proteome machine (GPM) can be used for protein identification and for validation of the results. We cover identification by searching protein sequence collections and s ...