Construction of Line Densities for Parallel Coordinate Plots

The graphical representation of high dimensional data may be accomplished by using the parallel coordinate plotting system. In such a representation points in Euclidian n-space are mapped into line segments in Euclidian 2-space by a projective transformation. This representation preserves much of the geometric structure found in hyperspace but not easily representable by other methods. In large data set applications, the graphical displays may be heavily overplotted like ordinary scatterplots yielding uninterpretable displays. In this paper, we suggest replacing the raw data display with a density plot. In order to define densities for lines sensibly, we introduce the notion of line densities and develop their basic construction. We illustrate with theoretical parallel coordinate density plots for the normal and the uniform cases. Finally we illustrate sample density plots with 4-dimensional spheres

Dynamic combinatorial mass spectrometry leads to inhibitors of a 2-oxoglutarate-dependent nucleic acid demethylase.

2-Oxoglutarate-dependent nucleic acid demethylases are of biological interest because of their roles in nucleic acid repair and modification. Although some of these enzymes are linked to physiology, their regulatory roles are unclear. Hence, there is a desire to develop selective inhibitors for them; we report studies on AlkB, which reveal it as being amenable to selective inhibition by small molecules. Dynamic combinatorial chemistry linked to mass spectrometric analyses (DCMS) led to the identification of lead compounds, one of which was analyzed by crystallography. Subsequent structure-guided studies led to the identification of inhibitors of improved potency, some of which were shown to be selective over two other 2OG oxygenases. The work further validates the use of the DCMS method and will help to enable the development of inhibitors of nucleic acid modifying 2OG oxygenases both for use as functional probes and, in the longer term, for potential therapeutic use