Structural basis for the shielding function of the dynamic trypanosome variant surface glycoprotein coat.

The most prominent defence of the unicellular parasite Trypanosoma brucei against the host immune system is a dense coat that comprises a variant surface glycoprotein (VSG). Despite the importance of the VSG family, no complete structure of a VSG has been reported. Making use of high-resolution structures of individual VSG domains, we employed small-angle X-ray scattering to elucidate the first two complete VSG structures. The resulting models imply that the linker regions confer great flexibility between domains, which suggests that VSGs can adopt two main conformations to respond to obstacles and changes of protein density, while maintaining a protective barrier at all times. Single-molecule diffusion measurements of VSG in supported lipid bilayers substantiate this possibility, as two freely diffusing populations could be detected. This translates into a highly flexible overall topology of the surface VSG coat, which displays both lateral movement in the plane of the membrane and variation in the overall thickness of the coat.

Learning interpretable SVMs for biological sequence classification.

BACKGROUND: Support Vector Machines (SVMs)--using a variety of string kernels--have been successfully applied to biological sequence classification problems. While SVMs achieve high classification accuracy they lack interpretability. In many applications, it does not suffice that an algorithm just detects a biological signal in the sequence, but it should also provide means to interpret its solution in order to gain biological insight. RESULTS: We propose novel and efficient algorithms for solving the so-called Support Vector Multiple Kernel Learning problem. The developed techniques can be used to understand the obtained support vector decision function in order to extract biologically relevant knowledge about the sequence analysis problem at hand. We apply the proposed methods to the task of acceptor splice site prediction and to the problem of recognizing alternatively spliced exons. Our algorithms compute sparse weightings of substring locations, highlighting which parts of the sequence are important for discrimination. CONCLUSION: The proposed method is able to deal with thousands of examples while combining hundreds of kernels within reasonable time, and reliably identifies a few statistically significant positions.

BCI Competition 2003--Data set III: probabilistic modeling of sensorimotor mu rhythms for classification of imaginary hand movements.

Brain-computer interfaces require effective online processing of electroencephalogram (EEG) measurements, e.g., as a part of feedback systems. We present an algorithm for single-trial online classification of imaginary left and right hand movements, based on time-frequency information derived from filtering EEG wideband raw data with causal Morlet wavelets, which are adapted to individual EEG spectra. Since imaginary hand movements lead to perturbations of the ongoing pericentral mu rhythm, we estimate probabilistic models for amplitude modulation in lower (10 Hz) and upper (20 Hz) frequency bands over the sensorimotor hand cortices both contra- and ipsilaterally to the imagined movements (i.e., at EEG channels C3 and C4). We use an integrative approach to accumulate over time evidence for the subject's unknown motor intention. Disclosure of test data labels after the competition showed this approach to succeed with an error rate as low as 10.7%.

Boosting bit rates and error detection for the classification of fast-paced motor commands based on single-trial EEG analysis.

Brain-computer interfaces (BCIs) involve two coupled adapting systems--the human subject and the computer. In developing our BCI, our goal was to minimize the need for subject training and to impose the major learning load on the computer. To this end, we use behavioral paradigms that exploit single-trial EEG potentials preceding voluntary finger movements. Here, we report recent results on the basic physiology of such premovement event-related potentials (ERP). 1) We predict the laterality of imminent left- versus right-hand finger movements in a natural keyboard typing condition and demonstrate that a single-trial classification based on the lateralized Bereitschaftspotential (BP) achieves good accuracies even at a pace as fast as 2 taps/s. Results for four out of eight subjects reached a peak information transfer rate of more than 15 b/min; the four other subjects reached 6-10 b/min. 2) We detect cerebral error potentials from single false-response trials in a forced-choice task, reflecting the subject's recognition of an erroneous response. Based on a specifically tailored classification procedure that limits the rate of false positives at, e.g., 2%, the algorithm manages to detect 85% of error trials in seven out of eight subjects. Thus, concatenating a primary single-trial BP-paradigm involving finger classification feedback with such secondary error detection could serve as an efficient online confirmation/correction tool for improvement of bit rates in a future BCI setting. As the present variant of the Berlin BCI is designed to achieve fast classifications in normally behaving subjects, it opens a new perspective for assistance of action control in time-critical behavioral contexts; the potential transfer to paralyzed patients will require further study.