A Pseudolikelihood Approach for Simultaneous Analysis of Array Comparative Genomic Hybridizations (aCGH)

DNA sequence copy number has been shown to be associated with cancer development and progression. Array-based Comparative Genomic Hybridization (aCGH) is a recent development that seeks to identify the copy number ratio at large numbers of markers across the genome. Due to experimental and biological variations across chromosomes and across hybridizations, current methods are limited to analyses of single chromosomes. We propose a more powerful approach that borrows strength across chromosomes and across hybridizations. We assume a Gaussian mixture model, with a hidden Markov dependence structure, and with random effects to allow for intertumoral variation, as well as intratumoral clonal variation. For ease of computation, we base estimation on a pseudolikelihood function. The method produces quantitative assessments of the likelihood of genetic alterations at each clone, along with a graphical display for simple visual interpretation. We assess the characteristics of the method through simulation studies and through analysis of a brain tumor aCGH data set. We show that the pseudolikelihood approach is superior to existing methods both in detecting small regions of copy number alteration and in accurately classifying regions of change when intratumoral clonal variation is present

Imaging correlates of molecular signatures in oligodendrogliomas.

Molecular subsets of oligodendroglioma behave in biologically distinct ways. Their locations in the brain, rates of growth, and responses to therapy differ with their genotypes. Retrospectively, we inquired whether allelic loss of chromosomal arms 1p and 19q, an early molecular event and favorable prognostic marker in oligodendrogliomas, were reflected in their appearance on magnetic resonance imaging. Loss of 1p and 19q was associated with an indistinct border on T(1) images and mixed intensity signal on T(1) and T(2). Loss of 1p and 19q was also associated with paramagnetic susceptibility effect and with calcification, a common histopathological finding in oligodendrogliomas. These data encourage prospective evaluation of molecular alterations and magnetic resonance imaging characteristics of glial neoplasms

Multiple Quantum Oscillations in the de Haas van Alphen Spectra of the Underdoped High Temperature Superconductor YBa_2Cu_3O_6.5

By improving the experimental conditions and extensive data accumulation, we have achieved very high-precision in the measurements of the de Haas-van Alphen effect in the underdoped high-temperature superconductor YBa$_{2}$Cu$_{3}$O$_{6.5}$. We find that the main oscillation, so far believed to be single-frequency, is composed of three closely spaced frequencies. We attribute this to bilayer splitting and warping of a single quasi-2D Fermi surface, indicating that \emph{c}-axis coherence is restored at low temperature in underdoped cuprates. Our results do not support the existence of a larger frequency of the order of 1650 T reported recently in the same compound [S.E. Sebastian {\it et al}., Nature {\bf 454}, 200 (2008)]