CiteULike: Author Jörg

Kernel Functions for Attributed Molecular Graphs - A New Similarity-Based Approach to ADME Prediction in Classification and Regression

Holger Fröhlich — 2008-08-05T10:16:48-00:00

QSAR & Combinatorial Science, Vol. 25, No. 4. (2006), pp. 317-326.

Kernel methods, like the well-known Support Vector Machine (SVM), have received growing attention in recent years for designing QSAR models that have a high predictive strength. One of the key concepts of SVMs is the usage of a so-called kernel function, which can be thought of as a special similarity measure. In this paper we consider kernels for molecular structures, which are based on a graph representation of chemical compounds. The similarity score is calculated by computing an optimal assignment of the atoms from one molecule to those of another one, including information on specific chemical properties, membership to a substructure (e.g., aromatic ring, carbonyl group, etc.) and neighborhood for each atom. We show that by using this kernel we can achieve a generalization performance comparable to a classical model with a few descriptors, which are a-priori known to be relevant for the problem, and significantly better results than with and without performing an automatic descriptor selection. For this purpose we investigate ADME classification and regression datasets for predicting bioavailability (Yoshida), Human Intestinal Absorption (HIA), Blood-Brain-Barrier (BBB) penetration and a dataset consisting of four different inhibitor classes (SOL). We further explore the effect of combining our kernel with a problem-dependent descriptor set. We also demonstrate the usefulness of an extension of our method to a reduced graph representation of molecules, in which certain structural features, like, e.g., rings, donors or acceptors, are represented as a single node in the molecular graph.

Human tuberculous granulomas induce peripheral lymphoid follicle-like structures to orchestrate local host defence in the lung.

T Ulrichs — 2008-06-16T16:43:46-00:00

The Journal of pathology, Vol. 204, No. 2. (October 2004), pp. 217-228.

The human tuberculous granuloma provides the morphological basis for local immune processes central to the outcome of tuberculosis. Because of the scarcity of information in human patients, the aim of the present study was to gain insights into the functional and structural properties of infiltrated tissue. To this end, the mycobacterial load in lesions and dissemination to different tissue locations were investigated, as well as distribution, biological functions, and interactions of host immune cells. Analysis of early granuloma formation in formerly healthy lung tissue revealed a spatio-temporal sequence of cellular infiltration to sites of mycobacterial infection. A general structure of the developing granuloma was identified, comprising an inner cell layer with few CD8(+) cells surrounding the necrotic centre and an outer area of lymphocyte infiltration harbouring mycobacteria-containing antigen-presenting cells as well as CD4(+), CD8(+), and B cells in active follicle-like centres resembling secondary lymphoid organs. It is concluded that the follicular structures in the peripheral rim of granulomas serve as a morphological substrate for the orchestration of the enduring host response in pulmonary tuberculosis.

Towards a new, complexity science of learning and education

T Jörg — 2008-05-19T20:02:36-00:00

Educational Research Review, Vol. 2, No. 2. (2007), pp. 145-156.