Discovering Conformational Sub-States Relevant to Protein Function

Background: Internal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states) contain properties that may be functionally relevant. However, low populations in these sub-states and the transient nature of conformational transitions between these substates present significant challenges for their identification and characterization. Methods and Findings: To overcome these challenges we have developed a new computational technique, quasianharmonic analysis (QAA). QAA utilizes higher-order statistics of protein motions to identify sub-states in the conformational landscape. Further, the focus on anharmonicity allows identification of conformational fluctuations that enable transitions between sub-states. QAA applied to equilibrium simulations of human ubiquitin and T4 lysozyme reveals functionally relevant sub-states and protein motions involved in molecular recognition. In combination with a reaction pathway sampling method, QAA characterizes conformational sub-states associated with cis/trans peptidyl-prolyl isomerization catalyzed by the enzyme cyclophilin A. In these three proteins, QAA allows identification of conformational sub-states, with critical structural and dynamical features relevant to protein function. Conclusions: Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function. © 2011 Ramanathan et al

Estimation of white matter fiber parameters from compressed multiresolution diffusion MRI using sparse Bayesian learning

We present a sparse Bayesian unmixing algorithm BusineX: Bayesian Unmixing for Sparse Inference-based Estimation of Fiber Crossings (X), for estimation of white matter fiber parameters from compressed (under-sampled) diffusion MRI (dMRI) data. BusineX combines compressive sensing with linear unmixing and introduces sparsity to the previously proposed multiresolution data fusion algorithm RubiX, resulting in a method for improved reconstruction, especially from data with lower number of diffusion gradients. We formulate the estimation of fiber parameters as a sparse signal recovery problem and propose a linear unmixing framework with sparse Bayesian learning for the recovery of sparse signals, the fiber orientations and volume fractions. The data is modeled using a parametric spherical deconvolution approach and represented using a dictionary created with the exponential decay components along different possible diffusion directions. Volume fractions of fibers along these directions define the dictionary weights. The proposed sparse inference, which is based on the dictionary representation, considers the sparsity of fiber populations and exploits the spatial redundancy in data representation, thereby facilitating inference from under-sampled q-space. The algorithm improves parameter estimation from dMRI through data-dependent local learning of hyperparameters, at each voxel and for each possible fiber orientation, that moderate the strength of priors governing the parameter variances. Experimental results on synthetic and in-vivo data show improved accuracy with a lower uncertainty in fiber parameter estimates. BusineX resolves a higher number of second and third fiber crossings. For under-sampled data, the algorithm is also shown to produce more reliable estimates

Non-parametric estimation of finite mixtures from repeated measurements

SummaryThis paper provides methods to estimate finite mixtures from data with repeated measurements non-parametrically. We present a constructive identification argument and use it to develop simple two-step estimators of the component distributions and all their functionals. We discuss a computationally efficient method for estimation and derive asymptotic theory. Simulation experiments suggest that our theory provides confidence intervals with good coverage in small samples.</jats:p

Independent EEG Sources Are Dipolar

Independent component analysis (ICA) and blind source separation (BSS) methods are increasingly used to separate individual brain and non-brain source signals mixed by volume conduction in electroencephalographic (EEG) and other electrophysiological recordings. We compared results of decomposing thirteen 71-channel human scalp EEG datasets by 22 ICA and BSS algorithms, assessing the pairwise mutual information (PMI) in scalp channel pairs, the remaining PMI in component pairs, the overall mutual information reduction (MIR) effected by each decomposition, and decomposition ‘dipolarity’ defined as the number of component scalp maps matching the projection of a single equivalent dipole with less than a given residual variance. The least well-performing algorithm was principal component analysis (PCA); best performing were AMICA and other likelihood/mutual information based ICA methods. Though these and other commonly-used decomposition methods returned many similar components, across 18 ICA/BSS algorithms mean dipolarity varied linearly with both MIR and with PMI remaining between the resulting component time courses, a result compatible with an interpretation of many maximally independent EEG components as being volume-conducted projections of partially-synchronous local cortical field activity within single compact cortical domains. To encourage further method comparisons, the data and software used to prepare the results have been made available (http://sccn.ucsd.edu/wiki/BSSComparison)

Independent component analysis and source analysis of auditory evoked potentials for assessment of cochlear implant users

Source analysis of the Auditory Evoked Potential (AEP) has been used before to evaluate the maturation of the auditory system in both adult and children; in the same way, this technique could be applied to ongoing EEG recordings, in response to acoustic specific frequency stimuli, from children with cochlear implants (CI). This is done in oder to objectively assess the performance of this electronic device and the maturation of the child?s hearing. However, these recordings are contaminated by an artifact produced by the normal operation of the CI; this artifact in particular makes the detection and analysis of AEPs much harder and generates errors in the source analysis process. The artifact can be spatially filtered using Independent Component Analysis (ICA); in this research, three different ICA algorithms were compared in order to establish the more suited algorithm to remove the CI artifact. Additionally, we show that pre-processing the EEG recording, using a temporal ICA algorithm, facilitates not only the identification of the AEP peaks but also the source analysis procedure. From results obtained in this research and limited dataset of CI vs normal recordings, it is possible to conclude that the AEPs source locations change from the inferior temporal areas in the first 2 years after implantation to the superior temporal area after three years using the CIs, close to the locations obtained in normal hearing children. It is intended that the results of this research are used as an objective technique for a general evaluation of the performance of children with CIs

Proceedings of the 2011 New York Workshop on Computer, Earth and Space Science

The purpose of the New York Workshop on Computer, Earth and Space Sciences is to bring together the New York area's finest Astronomers, Statisticians, Computer Scientists, Space and Earth Scientists to explore potential synergies between their respective fields. The 2011 edition (CESS2011) was a great success, and we would like to thank all of the presenters and participants for attending. This year was also special as it included authors from the upcoming book titled "Advances in Machine Learning and Data Mining for Astronomy". Over two days, the latest advanced techniques used to analyze the vast amounts of information now available for the understanding of our universe and our planet were presented. These proceedings attempt to provide a small window into what the current state of research is in this vast interdisciplinary field and we'd like to thank the speakers who spent the time to contribute to this volume.Comment: Author lists modified. 82 pages. Workshop Proceedings from CESS 2011 in New York City, Goddard Institute for Space Studie