Data visualization during the early stages of drug discovery

Multidimensional compound optimization is a new paradigm in the drug discovery process, yielding efficiencies during early stages and reducing attrition in the later stages of drug development. The success of this strategy relies heavily on understanding this multidimensional data and extracting useful information from it. This paper demonstrates how principled visualization algorithms can be used to understand and explore a large data set created in the early stages of drug discovery. The experiments presented are performed on a real-world data set comprising biological activity data and some whole-molecular physicochemical properties. Data visualization is a popular way of presenting complex data in a simpler form. We have applied powerful principled visualization methods, such as generative topographic mapping (GTM) and hierarchical GTM (HGTM), to help the domain experts (screening scientists, chemists, biologists, etc.) understand and draw meaningful decisions. We also benchmark these principled methods against relatively better known visualization approaches, principal component analysis (PCA), Sammon's mapping, and self-organizing maps (SOMs), to demonstrate their enhanced power to help the user visualize the large multidimensional data sets one has to deal with during the early stages of the drug discovery process. The results reported clearly show that the GTM and HGTM algorithms allow the user to cluster active compounds for different targets and understand them better than the benchmarks. An interactive software tool supporting these visualization algorithms was provided to the domain experts. The tool facilitates the domain experts by exploration of the projection obtained from the visualization algorithms providing facilities such as parallel coordinate plots, magnification factors, directional curvatures, and integration with industry standard software. © 2006 American Chemical Society.

Performance management in the United States and France:four case studies in the retail and airline industries

The profusion of performance measurement models suggested by Management Accounting literature in the 1990’s is one illustration of the substantial changes in Management Accounting teaching materials since the publication of “Relevance Lost” in 1987. At the same time, in the general context of increasing competition and globalisation it is widely thought that national cultural differences are tending to disappear, meaning that management techniques used in large companies, including performance measurement and management instruments (PMS), tend to be the same, irrespective of the company nationality or location. North American management practice is traditionally described as a contractually based model, mainly focused on financial performance information and measures (FPMs), more shareholder-focused than French companies. Within France, literature historically defined performance as being broadly multidimensional, driven by the idea that there are no universal rules of management and that efficient management takes into account local culture and traditions. As opposed to their North American brethren, French companies are pressured more by the financial institutions that fund them rather than by capital markets. Therefore, they pay greater attention to the long-term because they are not subject to quarterly capital market objectives. Hence, management in France should rely more on long-term qualitative information, less financial, and more multidimensional data to assess performance than their North American counterparts. The objective of this research is to investigate whether large French and US companies’ practices have changed in the way the textbooks have changed with regards to performance measurement and management, or whether cultural differences are still driving differences in performance measurement and management between them. The research findings support the idea that large US and French companies share the same PMS features, influenced by ‘universal’ PM models.

MILVA:An interactive tool for the exploration of multidimensional microarray data

Clustering techniques such as k-means and hierarchical clustering are commonly used to analyze DNA microarray derived gene expression data. However, the interactions between processes underlying the cell activity suggest that the complexity of the microarray data structure may not be fully represented with discrete clustering methods.

Artefactual structure from least squares multidimensional scaling

We consider the problem of illusory or artefactual structure from the visualisation of high-dimensional structureless data. In particular we examine the role of the distance metric in the use of topographic mappings based on the statistical field of multidimensional scaling. We show that the use of a squared Euclidean metric (i.e. the SSTRESs measure) gives rise to an annular structure when the input data is drawn from a high-dimensional isotropic distribution, and we provide a theoretical justification for this observation.

Feed-forward neural networks and topographic mappings for exploratory data analysis

A recent novel approach to the visualisation and analysis of datasets, and one which is particularly applicable to those of a high dimension, is discussed in the context of real applications. A feed-forward neural network is utilised to effect a topographic, structure-preserving, dimension-reducing transformation of the data, with an additional facility to incorporate different degrees of associated subjective information. The properties of this transformation are illustrated on synthetic and real datasets, including the 1992 UK Research Assessment Exercise for funding in higher education. The method is compared and contrasted to established techniques for feature extraction, and related to topographic mappings, the Sammon projection and the statistical field of multidimensional scaling.

Developing multidimensional metrics for evaluating paediatric neurodevelopmental disorders

Healthy brain functioning depends on efficient communication of information between brain regions, forming complex networks. By quantifying synchronisation between brain regions, a functionally connected brain network can be articulated. In neurodevelopmental disorders, where diagnosis is based on measures of behaviour and tasks, a measure of the underlying biological mechanisms holds promise as a potential clinical tool. Graph theory provides a tool for investigating the neural correlates of neuropsychiatric disorders, where there is disruption of efficient communication within and between brain networks. This research aimed to use recent conceptualisation of graph theory, along with measures of behaviour and cognitive functioning, to increase understanding of the neurobiological risk factors of atypical development. Using magnetoencephalography to investigate frequency-specific temporal dynamics at rest, the research aimed to identify potential biological markers derived from sensor-level whole-brain functional connectivity. Whilst graph theory has proved valuable for insight into network efficiency, its application is hampered by two limitations. First, its measures have hardly been validated in MEG studies, and second, graph measures have been shown to depend on methodological assumptions that restrict direct network comparisons. The first experimental study (Chapter 3) addressed the first limitation by examining the reproducibility of graph-based functional connectivity and network parameters in healthy adult volunteers. Subsequent chapters addressed the second limitation through adapted minimum spanning tree (a network analysis approach that allows for unbiased group comparisons) along with graph network tools that had been shown in Chapter 3 to be highly reproducible. Network topologies were modelled in healthy development (Chapter 4), and atypical neurodevelopment (Chapters 5 and 6). The results provided support to the proposition that measures of network organisation, derived from sensor-space MEG data, offer insights helping to unravel the biological basis of typical brain maturation and neurodevelopmental conditions, with the possibility of future clinical utility.

Improved data visualisation through multiple dissimilarity modelling

Popular dimension reduction and visualisation algorithms rely on the assumption that input dissimilarities are typically Euclidean, for instance Metric Multidimensional Scaling, t-distributed Stochastic Neighbour Embedding and the Gaussian Process Latent Variable Model. It is well known that this assumption does not hold for most datasets and often high-dimensional data sits upon a manifold of unknown global geometry. We present a method for improving the manifold charting process, coupled with Elastic MDS, such that we no longer assume that the manifold is Euclidean, or of any particular structure. We draw on the benefits of different dissimilarity measures allowing for the relative responsibilities, under a linear combination, to drive the visualisation process.