Biomedical subjects

A van der Vaart

Publications and source records attributed to A van der Vaart.

3 recordsLinked to original sources

PubMed2006

Cross-platform array comparative genomic hybridization meta-analysis separates hematopoietic and mesenchymal from epithelial tumors.

A series of studies have been published that evaluate the chromosomal copy number changes of different tumor classes using array comparative genomic hybridization (array CGH); however, the chromosomal aberrations that distinguish the different tumor classes have not been fully characterized. Therefore, we performed a meta-analysis of different array CGH data sets in an attempt to classify samples tested across different platforms. As opposed to RNA expression, a common reference is used in dual channel CGH arrays: normal human DNA, theoretically facilitating cross-platform analysis. To this aim, cell line and primary cancer data sets from three different dual channel array CGH platforms obtained by four different institutes were integrated. The cell line data were used to develop preprocessing methods, which performed noise reduction and transformed samples into a common format. The transformed array CGH profiles allowed perfect clustering by cell line, but importantly not by platform or institute. The same preprocessing procedures used for the cell line data were applied to data from 373 primary tumors profiled by array CGH, including controls. Results indicated that there is no apparent feature related to the institute or platform and that array CGH allows for unambiguous cross-platform meta-analysis. Major clusters with common tissue origin were identified. Interestingly, tumors of hematopoietic and mesenchymal origins cluster separately from tumors of epithelial origin. Therefore, it can be concluded that chromosomal aberrations of tumors from hematopoietic and mesenchymal origin versus tumors of epithelial origin are distinct, and these differences can be picked up by meta-analysis of array CGH data. This suggests the possibility of prospectively using combined analysis of diverse copy number data sets for cancer subtype classification.

Chromosome Aberrations↗

PubMed2005

Simulation of liquid water using semiempirical Hamiltonians and the divide and conquer approach.

This work examines the ability of semiempirical methods to describe the structure of liquid water. Particularly, the standard AM1 and PM3 methods together with recently developed PM3-PIF and PM3-MAIS parametrizations have been considered. We perform molecular dynamics simulations for a system consisting of 64 or 216 water molecules in a periodic cubic box. The whole system is described quantum mechanically. Calculations with 64 molecules have been carried out using standard SCF techniques whereas calculations with 216 molecules have been done using the divide and conquer approach. This method has also been used in one simulation case with 64 molecules for test purposes. Within this scope, the molecular dynamics program ROAR have been coupled with a linear scaling semiempirical code (DivCon) implemented in a parallel MPI version. The predicted liquid water structure using either AM1 or PM3 is shown to be very poor due to well-known limitations of these methods describing hydrogen bonds. In contrast, PM3-PIF and PM3-MAIS calculations lead to results in reasonably good agreement with experimental data. The best results for the heat of vaporization are obtained with the PM3-PIF method. The average induced dipole moment of the water molecule in the liquid is underestimated by all semiempirical techniques, which seems to be related to the NDDO approximation and to the use of minimal basis sets. A brief discussion on charge-transfer effects in liquid water is also presented.

Computer Simulation↗

PubMed2001

New developments in applying quantum mechanics to proteins.

Algorithmic improvements of quantum mechanical methodologies have increased our ability to study the electronic structure of fragments of a biomolecule (e.g. an enzyme active site) or entire biomolecules. Three main strategies have emerged as ways in which quantum mechanics can be applied to biomolecules. The supermolecule approach continues to be utilized, but it is slowly being replaced by the so-called coupled quantum mechanical/molecular mechanical methodologies. An exciting new direction is the continued development and application of linear-scaling quantum mechanical approaches to biomolecular systems.

Algorithms↗