Gene expression data annotation, effective storage, and enrichment through data mining

This thesis describes the development of different bioinformatics resources and data-mining strategies for managing and analysing the large amounts of data produced by microarray gene expression experiments. Initially, this involved addressing the problem of effectively capturing gene expression microarray data and the accompanying meta-data annotations de scribing the experimental process. This is necessary for reasons of archiving, interchange and reproducibility of datasets and comparability between them. This was achieved by the development of meditor, a graphical computer programme which allows the description of microarray experimental information through the use of diagrams and ontology-driven forms, meditor adheres to the standards set by the Microarray Gene Expression Data Society (MGED), and therefore is able to capture all the experimental information describable within the standard in a platform-independent manner. Subsequently, in order to provide capabilities for the formal modelling of gene expression analysis concepts, the concepts involved in the external validation of gene expression clusterings were formalised and defined as an object model. This model was developed with the implementation of data interchange file formats in mind. This work complements the object model of the MGED Society and attempts to cover an area that has not been formalised in a platform-independent manner by the standard object model. Finally, a method was developed to allow the use of knowledge on protein functions and protein-protein interactions to identify coherent sets of co-regulated genes suggested by the clustering of gene expression profiles. This was achieved through the development of a gene expression clustering quality metric, which judges the tightness and separation of gene expression clusters, thus providing a quality measure on a clustering or a per-cluster basis. Cluster tightness and separation are assessed by harnessing the manual annotations provided by the Gene Ontology, enriched using integrated biological information available through an in-house data warehouse (BioMap). The metric was tested on a human B-cell gene expression dataset and refined on the basis of the results produced

Transient chaos and resonant phase mixing in violent relaxation

This paper explores how orbits in a galactic potential can be impacted by large amplitude time-dependences of the form that one might associate with galaxy or halo formation or strong encounters between pairs of galaxies. A period of time-dependence with a strong, possibly damped, oscillatory component can give rise to large amounts of transient chaos, and it is argued that chaotic phase mixing associated with this transient chaos could play a major role in accounting for the speed and efficiency of violent relaxation. Analysis of simple toy models involving time-dependent perturbations of an integrable Plummer potential indicates that this chaos results from a broad, possibly generic, resonance between the frequencies of the orbits and harmonics thereof and the frequencies of the time-dependent perturbation. Numerical computations of orbits in potentials exhibiting damped oscillations suggest that, within a period of 10 dynamical times t_D or so, one could achieve simultaneously both `near-complete' chaotic phase mixing and a nearly time-independent, integrable end state.Comment: 11 pages and 12 figures: an extended version of the original manuscript, containing a modified title, one new figure, and approximately one page of additional text, to appear in Monthly Notices of the Royal Astronomical Societ

Multivariable stability margin calculation with uncertain correlated parameters

An algorithm is developed for the computation of the multivariable stability margin in the case of real uncertain system parameters which can be related to each other

Smooth potential chaos and N-body simulations

Integrations in fixed N-body realisations of smooth density distributions corresponding to a chaotic galactic potential can be used to derive reliable estimates of the largest (finite time) Lyapunov exponent X_S associated with an orbit in the smooth potential generated from the same initial condition, even though the N-body orbit is typically characterised by an N-body exponent X_N >> X_S. This can be accomplished either by comparing initially nearby orbits in a single N-body system or by tracking orbits with the same initial condition evolved in two different N-body realisations of the same smooth density.Comment: 9 pages plus 7 figures, expanded version to appear in Astrophysical Journa

Dynamics of Cuspy Triaxial Galaxies with a Supermassive Black Hole

This talk provides a progress report on an extended collaboration which has aimed to address two basic questions, namely: Should one expect to see cuspy, triaxial galaxies in nature? And can one construct realistic cuspy, triaxial equilibrium models that are robust? Three technical results are described: (1) Unperturbed chaotic orbits in cuspy triaxial potentials can be extraordinarily sticky, much more so than orbits in many other three-dimensional potentials. (2) Even very weak perturbations can be important by drastically reducing, albeit not completely eliminating, this stickiness. (3) A simple toy model facilitates a simple understanding of why black holes and cusps can serve as an effective source of chaos. These results suggest that, when constructing models of galaxies using Schwarzschild's method or any analogue thereof, astronomers would be well advised to use orbital building blocks that have been perturbed by `noise' or other weak irregularities, since such building blocks are likely to be more nearly time-independent than orbits evolved in the absence of all perturbations.Comment: a contributed talk at The International Conference on Stellar Dynamics: From Classical to Modern, Sobolev Astronomical Institute, St. Petersburg State University, August 200

Developmental Markers of Genetic Liability to Autism in Parents: A Longitudinal, Multigenerational Study

Genetic liability to autism spectrum disorder (ASD) can be expressed in unaffected relatives through subclinical, genetically meaningful traits, or endophenotypes. This study aimed to identify developmental endophenotypes in parents of individuals with ASD by examining parents' childhood academic development over the school-age period. A cohort of 139 parents of individuals with ASD were studied, along with their children with ASD and 28 controls. Parents' childhood records in the domains of language, reading, and math were studied from grades K-12. Results indicated that relatively lower performance and slower development of skills (particularly language related skills), and an uneven rate of development across domains predicted ASD endophenotypes in adulthood for parents, and the severity of clinical symptoms in children with ASD. These findings may mark childhood indicators of genetic liability to ASD in parents, that could inform understanding of the subclinical expression of AS