Shing-Chung Ngan

Analysis of functional magnetic resonance imaging data using self-organizing mapping with spatial connectivity.

Commonly used methods in analyzing functional magnetic resonance imaging (fMRI) data, such as the Students t‐test and cross‐correlation analysis, are model‐based approaches. Although these methods are easy to implement and are effective in analyzing data obtained with simple paradigms, they are not applicable in situations in which patterns of neuronal response are complicated and when fMRI response is unknown. In this work, Kohonens self‐organizing mapping (SOM), which is a model‐free approach, is adapted for analyzing fMRI data. Because spatial connectivity is an important function in the identification of activation sites in functional brain imaging, it is incorporated into the SOM algorithm. Receiver operating characteristic analysis on simulated data shows that the new algorithm achieves measurable improvement over the standard algorithm. The applicability of the new algorithm is demonstrated on experimental data. Magn Reson Med 41:939–946, 1999.

PROTINFO: new algorithms for enhanced protein structure predictions

We describe new algorithms and modules for protein structure prediction available as part of the PROTINFO web server. The modules, comparative and de novo modelling, have significantly improved back-end algorithms that were rigorously evaluated at the sixth meeting on the Critical Assessment of Protein Structure Prediction methods. We were one of four server groups invited to make an oral presentation (only the best performing groups are asked to do so). These two modules allow a user to submit a protein sequence and return atomic coordinates representing the tertiary structure of that protein. The PROTINFO server is available at .

Wavelet transform-based Wiener filtering of event-related fMRI data

The advent of event‐related functional magnetic resonance imaging (fMRI) has resulted in many exciting studies that have exploited its unique capability. However, the utility of event‐related fMRI is still limited by several technical difficulties. One significant limitation in event‐related fMRI is the low signal‐to‐noise ratio (SNR). In this work, a method based on Wiener filtering in the wavelet domain is developed and demonstrated for denoising event‐related fMRI data. Application of the technique to simulated and experimental data demonstrates that the technique is effective in reducing noise while preserving neuronal activity‐induced response. Magn Reson Med 44:746–757, 2000.

A knowledge-based scoring function based on residue triplets for protein structure prediction

Abstract One of the general paradigms for ab initio protein structure prediction involves sampling the conformational space such that a large set of decoy (candidate) structures are generated and then selecting native-like conformations from those decoys using various scoring functions. In this study, based on a physical/geometric approach first suggested by Banavar and colleagues, we formulate a knowledge-based scoring function, which uses the radii of curvature formed among triplets of residues in a protein conformation. By analyzing its performance on various decoy sets, we determine a good set of parameters—the distance cutoff and the number of distance bins—to use for configuring such a function. Furthermore, we investigate the effect of using various approaches for compiling the prior distribution on the performance of the knowledge-based function. Possible extensions to the current form of the residue triplet scoring function are discussed.

Temporal filtering of event-related fMRI data using cross-validation

To circumvent the problem of low signal-to-noise ratio (SNR) in event-related fMRI data, the fMRI experiment is typically designed to consist of repeated presentations of the stimulus and measurements of the response, allowing for subsequent averaging of the resulting data. Due to factors such as time limitation, subject motion, habituation, and fatigue, practical constraints on the number of repetitions exist. Thus, filtering is commonly applied to further improve the SNR of the averaged data. Here, a time-varying filter based on theoretical work by Nowak is employed. This filter operates under the stationary wavelet transform framework and is demonstrated to lead to good estimates of the true signals in simulated data. The utility of the filter is also shown using experimental data obtained with a visual-motor paradigm.

Activation detection in event-related fMRI data based on spatio-temporal properties.

Template-based activation detection methods, such as cross-correlation, could be difficult to apply in event-related functional MRI data because accurate a priori knowledge about the activation signal patterns is often not available. As a result, several categories of template-free data analysis techniques have been introduced in the fMRI literature. One previously described template-free activation detection technique is based on the feature that activated voxels yield reproducible time course patterns as the subject undergoes the same simulation in repeated epochs. In this paper, spatial information is incorporated as a second feature and a combined univariate measure is formed. The resulting method is shown to offer measurable improvement in detecting activation regions in simulated data in a highly computationally efficient manner. Its practical utility is demonstrated with an experimental data set obtained with a visually guided motor paradigm.

Improvement of spectral density-based activation detection of event-related fMRI data

For event-related data obtained from an experimental paradigm with a periodic design, spectral density at the fundamental frequency of the paradigm has been used as a template-free activation detection measure. In this article, we build and expand upon this detection measure to create an improved, integrated measure. Such an integrated measure linearly combines information contained in the spectral densities at the fundamental frequency as well as the harmonics of the paradigm and in a spatial correlation function characterizing the degree of co-activation among neighboring voxels. Several figures of merit are described and used to find appropriate values for the coefficients in the linear combination. Using receiver-operating characteristic analysis on simulated functional magnetic resonance imaging (fMRI) data sets, we quantify and validate the improved performance of the integrated measure over the spectral density measure based on the fundamental frequency as well as over some other popular template-free data analysis methods. We then demonstrate the application of the new method on an experimental fMRI data set. Finally, several extensions to this work are suggested.

De Novo Protein Structure Prediction

An unparalleled amount of sequence data is being made available from large-scale genome sequencing efforts. The data provide a shortcut to the determination of the function of a gene of interest, as long as there is an existing sequenced gene with similar sequence and of known function. This has spurred structural genomic initiatives with the goal of determining as many protein folds as possible (Brenner and Levitt, 2000; Burley, 2000; Brenner, 2001; Heinemann et al., 2001). The purpose of this is twofold: First, the structure of a gene product can often lead to direct inference of its function. Second, since the function of a protein is dependent on its structure, direct comparison of the structures of gene products can be more sensitive than the comparison of sequences of genes for detecting homology. Presently, structural determination by crystallography and NMR techniques is still slow and expensive in terms of manpower and resources, despite attempts to automate the processes. Computer structure prediction algorithms, while not providing the accuracy of the traditional techniques, are extremely quick and inexpensive and can provide useful low-resolution data for structure comparisons (Bonneau and Baker, 2001). Given the immense number of structures which the structural genomic projects are attempting to solve, there would be a considerable gain even if the computer structure prediction approach were applicable to a subset of proteins.

Nonadditive Two-Way ANOVA for Event-Related fMRI Data Analysis

A significant recent development in functional magnetic resonance imaging (fMRI) is the introduction of event-related fMRI, also known as time-resolved fMRI. Because the exact shape of the MR response in an event-related fMRI experiment is often not known, traditional methods developed for block design experiments, such as t test and correlation analysis, are not well-suited for extracting activated pixels from the event-related data. In this work, a statistical technique based on nonadditive two-way analysis of variance is developed for use in event-related studies. Theoretical and experimental work were carried out for establishing a statistical threshold to determine pixel activation. Experimental studies were performed to demonstrate the utility of this approach.

Detecting nonlinear dynamics of functional connectivity

Functional magnetic resonance imaging (fMRI) is a technique that is sensitive to correlates of neuronal activity. The application of fMRI to measure functional connectivity of related brain regions across hemispheres (e.g. left and right motor cortices) has great potential for revealing fundamental physiological brain processes. Primarily, functional connectivity has been characterized by linear correlations in resting-state data, which may not provide a complete description of its temporal properties. In this work, we broaden the measure of functional connectivity to study not only linear correlations, but also those arising from deterministic, non-linear dynamics. Here the delta-epsilon approach is extended and applied to fMRI time series. The method of delays is used to reconstruct the joint system defined by a reference pixel and a candidate pixel. The crux of this technique relies on determining whether the candidate pixel provides additional information concerning the time evolution of the reference. As in many correlation-based connectivity studies, we fix the reference pixel. Every brain location is then used as a candidate pixel to estimate the spatial pattern of deterministic coupling with the reference. Our results indicate that measured connectivity is often emphasized in the motor cortex contra-lateral to the reference pixel, demonstrating the suitability of this approach for functional connectivity studies. In addition, discrepancies with traditional correlation analysis provide initial evidence for non-linear dynamical properties of resting-state fMRI data. Consequently, the non-linear characterization provided from our approach may provide a more complete description of the underlying physiology and brain function measured by this type of data.