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2006


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Structure validation of the Josephin domain of ataxin-3: Conclusive evidence for an open conformation

Nicastro, G., Habeck, M., Masino, L., Svergun, DI., Pastore, A.

Journal of Biomolecular NMR, 36(4):267-277, December 2006 (article)

Abstract
The availability of new and fast tools in structure determination has led to a more than exponential growth of the number of structures solved per year. It is therefore increasingly essential to assess the accuracy of the new structures by reliable approaches able to assist validation. Here, we discuss a specific example in which the use of different complementary techniques, which include Bayesian methods and small angle scattering, resulted essential for validating the two currently available structures of the Josephin domain of ataxin-3, a protein involved in the ubiquitin/proteasome pathway and responsible for neurodegenerative spinocerebellar ataxia of type 3. Taken together, our results demonstrate that only one of the two structures is compatible with the experimental information. Based on the high precision of our refined structure, we show that Josephin contains an open cleft which could be directly implicated in the interaction with polyubiquitin chains and other partners.

ei

Web DOI [BibTex]

2006


Web DOI [BibTex]


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A Unifying View of Wiener and Volterra Theory and Polynomial Kernel Regression

Franz, M., Schölkopf, B.

Neural Computation, 18(12):3097-3118, December 2006 (article)

Abstract
Volterra and Wiener series are perhaps the best understood nonlinear system representations in signal processing. Although both approaches have enjoyed a certain popularity in the past, their application has been limited to rather low-dimensional and weakly nonlinear systems due to the exponential growth of the number of terms that have to be estimated. We show that Volterra and Wiener series can be represented implicitly as elements of a reproducing kernel Hilbert space by utilizing polynomial kernels. The estimation complexity of the implicit representation is linear in the input dimensionality and independent of the degree of nonlinearity. Experiments show performance advantages in terms of convergence, interpretability, and system sizes that can be handled.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Minimal Logical Constraint Covering Sets

Sinz, F., Schölkopf, B.

(155), Max Planck Institute for Biological Cybernetics, Tübingen, December 2006 (techreport)

Abstract
We propose a general framework for computing minimal set covers under class of certain logical constraints. The underlying idea is to transform the problem into a mathematical programm under linear constraints. In this sense it can be seen as a natural extension of the vector quantization algorithm proposed by Tipping and Schoelkopf. We show which class of logical constraints can be cast and relaxed into linear constraints and give an algorithm for the transformation.

ei

PDF [BibTex]

PDF [BibTex]


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New Methods for the P300 Visual Speller

Biessmann, F.

(1), (Editors: Hill, J. ), Max-Planck Institute for Biological Cybernetics, Tübingen, Germany, November 2006 (techreport)

ei

PDF [BibTex]

PDF [BibTex]


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Statistical Analysis of Slow Crack Growth Experiments

Pfingsten, T., Glien, K.

Journal of the European Ceramic Society, 26(15):3061-3065, November 2006 (article)

Abstract
A common approach for the determination of Slow Crack Growth (SCG) parameters are the static and dynamic loading method. Since materials with small Weibull module show a large variability in strength, a correct statistical analysis of the data is indispensable. In this work we propose the use of the Maximum Likelihood method and a Baysian analysis, which, in contrast to the standard procedures, take into account that failure strengths are Weibull distributed. The analysis provides estimates for the SCG parameters, the Weibull module, and the corresponding confidence intervals and overcomes the necessity of manual differentiation between inert and fatigue strength data. We compare the methods to a Least Squares approach, which can be considered the standard procedure. The results for dynamic loading data from the glass sealing of MEMS devices show that the assumptions inherent to the standard approach lead to significantly different estimates.

ei

PDF PDF DOI [BibTex]

PDF PDF DOI [BibTex]


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Mining frequent stem patterns from unaligned RNA sequences

Hamada, M., Tsuda, K., Kudo, T., Kin, T., Asai, K.

Bioinformatics, 22(20):2480-2487, October 2006 (article)

Abstract
Motivation: In detection of non-coding RNAs, it is often necessary to identify the secondary structure motifs from a set of putative RNA sequences. Most of the existing algorithms aim to provide the best motif or few good motifs, but biologists often need to inspect all the possible motifs thoroughly. Results: Our method RNAmine employs a graph theoretic representation of RNA sequences, and detects all the possible motifs exhaustively using a graph mining algorithm. The motif detection problem boils down to finding frequently appearing patterns in a set of directed and labeled graphs. In the tasks of common secondary structure prediction and local motif detection from long sequences, our method performed favorably both in accuracy and in efficiency with the state-of-the-art methods such as CMFinder.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Geometric Analysis of Hilbert Schmidt Independence criterion based ICA contrast function

Shen, H., Jegelka, S., Gretton, A.

(PA006080), National ICT Australia, Canberra, Australia, October 2006 (techreport)

ei

Web [BibTex]

Web [BibTex]


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Large-Scale Gene Expression Profiling Reveals Major Pathogenetic Pathways of Cartilage Degeneration in Osteoarthritis

Aigner, T., Fundel, K., Saas, J., Gebhard, P., Haag, J., Weiss, T., Zien, A., Obermayr, F., Zimmer, R., Bartnik, E.

Arthritis and Rheumatism, 54(11):3533-3544, October 2006 (article)

Abstract
Objective. Despite many research efforts in recent decades, the major pathogenetic mechanisms of osteo- arthritis (OA), including gene alterations occurring during OA cartilage degeneration, are poorly under- stood, and there is no disease-modifying treatment approach. The present study was therefore initiated in order to identify differentially expressed disease-related genes and potential therapeutic targets. Methods. This investigation consisted of a large gene expression profiling study performed based on 78 normal and disease samples, using a custom-made complementar y DNA array covering >4,000 genes. Results. Many differentially expressed genes were identified, including the expected up-regulation of ana- bolic and catabolic matrix genes. In particular, the down-regulation of important oxidative defense genes, i.e., the genes for superoxide dismutases 2 and 3 and glutathione peroxidase 3, was prominent. This indicates that continuous oxidative stress to the cells and the matrix is one major underlying pathogenetic mecha- nism in OA. Also, genes that are involved in the phenot ypic stabilit y of cells, a feature that is greatly reduced in OA cartilage, appeared to be suppressed. Conclusion. Our findings provide a reference data set on gene alterations in OA cartilage and, importantly, indicate major mechanisms underlying central cell bio- logic alterations that occur during the OA disease process. These results identify molecular targets that can be further investigated in the search for therapeutic interventions.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Implicit Surface Modelling with a Globally Regularised Basis of Compact Support

Walder, C., Schölkopf, B., Chapelle, O.

Computer Graphics Forum, 25(3):635-644, September 2006 (article)

Abstract
We consider the problem of constructing a globally smooth analytic function that represents a surface implicitly by way of its zero set, given sample points with surface normal vectors. The contributions of the paper include a novel means of regularising multi-scale compactly supported basis functions that leads to the desirable interpolation properties previously only associated with fully supported bases. We also provide a regularisation framework for simpler and more direct treatment of surface normals, along with a corresponding generalisation of the representer theorem lying at the core of kernel-based machine learning methods. We demonstrate the techniques on 3D problems of up to 14 million data points, as well as 4D time series data and four-dimensional interpolation between three-dimensional shapes.

ei

PDF GZIP DOI [BibTex]


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An Online Support Vector Machine for Abnormal Events Detection

Davy, M., Desobry, F., Gretton, A., Doncarli, C.

Signal Processing, 86(8):2009-2025, August 2006 (article)

Abstract
The ability to detect online abnormal events in signals is essential in many real-world Signal Processing applications. Previous algorithms require an explicit signal statistical model, and interpret abnormal events as statistical model abrupt changes. Corresponding implementation relies on maximum likelihood or on Bayes estimation theory with generally excellent performance. However, there are numerous cases where a robust and tractable model cannot be obtained, and model-free approaches need to be considered. In this paper, we investigate a machine learning, descriptor-based approach that does not require an explicit descriptors statistical model, based on Support Vector novelty detection. A sequential optimization algorithm is introduced. Theoretical considerations as well as simulations on real signals demonstrate its practical efficiency.

ei

PDF PostScript PDF DOI [BibTex]

PDF PostScript PDF DOI [BibTex]


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A tutorial on spectral clustering

von Luxburg, U.

(149), Max Planck Institute for Biological Cybernetics, Tübingen, August 2006 (techreport)

Abstract
In recent years, spectral clustering has become one of the most popular modern clustering algorithms. It is simple to implement, can be solved efficiently by standard linear algebra software, and very often outperforms traditional clustering algorithms such as the k-means algorithm. Nevertheless, on the first glance spectral clustering looks a bit mysterious, and it is not obvious to see why it works at all and what it really does. This article is a tutorial introduction to spectral clustering. We describe different graph Laplacians and their basic properties, present the most common spectral clustering algorithms, and derive those algorithms from scratch by several different approaches. Advantages and disadvantages of the different spectral clustering algorithms are discussed.

ei

PDF [BibTex]

PDF [BibTex]


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Integrating Structured Biological data by Kernel Maximum Mean Discrepancy

Borgwardt, K., Gretton, A., Rasch, M., Kriegel, H., Schölkopf, B., Smola, A.

Bioinformatics, 22(4: ISMB 2006 Conference Proceedings):e49-e57, August 2006 (article)

Abstract
Motivation: Many problems in data integration in bioinformatics can be posed as one common question: Are two sets of observations generated by the same distribution? We propose a kernel-based statistical test for this problem, based on the fact that two distributions are different if and only if there exists at least one function having different expectation on the two distributions. Consequently we use the maximum discrepancy between function means as the basis of a test statistic. The Maximum Mean Discrepancy (MMD) can take advantage of the kernel trick, which allows us to apply it not only to vectors, but strings, sequences, graphs, and other common structured data types arising in molecular biology. Results: We study the practical feasibility of an MMD-based test on three central data integration tasks: Testing cross-platform comparability of microarray data, cancer diagnosis, and data-content based schema matching for two different protein function classification schemas. In all of these experiments, including high-dimensional ones, MMD is very accurate in finding samples that were generated from the same distribution, and outperforms its best competitors. Conclusions: We have defined a novel statistical test of whether two samples are from the same distribution, compatible with both multivariate and structured data, that is fast, easy to implement, and works well, as confirmed by our experiments.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Towards the Inference of Graphs on Ordered Vertexes

Zien, A., Raetsch, G., Ong, C.

(150), Max Planck Institute for Biological Cybernetics, Tübingen, August 2006 (techreport)

Abstract
We propose novel methods for machine learning of structured output spaces. Specifically, we consider outputs which are graphs with vertices that have a natural order. We consider the usual adjacency matrix representation of graphs, as well as two other representations for such a graph: (a) decomposing the graph into a set of paths, (b) converting the graph into a single sequence of nodes with labeled edges. For each of the three representations, we propose an encoding and decoding scheme. We also propose an evaluation measure for comparing two graphs.

ei

PDF [BibTex]

PDF [BibTex]


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Large Scale Transductive SVMs

Collobert, R., Sinz, F., Weston, J., Bottou, L.

Journal of Machine Learning Research, 7, pages: 1687-1712, August 2006 (article)

Abstract
We show how the Concave-Convex Procedure can be applied to the optimization of Transductive SVMs, which traditionally requires solving a combinatorial search problem. This provides for the first time a highly scalable algorithm in the nonlinear case. Detailed experiments verify the utility of our approach.

ei

PostScript PDF PDF [BibTex]

PostScript PDF PDF [BibTex]


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Building Support Vector Machines with Reduced Classifier Complexity

Keerthi, S., Chapelle, O., DeCoste, D.

Journal of Machine Learning Research, 7, pages: 1493-1515, July 2006 (article)

Abstract
Support vector machines (SVMs), though accurate, are not preferred in applications requiring great classification speed, due to the number of support vectors being large. To overcome this problem we devise a primal method with the following properties: (1) it decouples the idea of basis functions from the concept of support vectors; (2) it greedily finds a set of kernel basis functions of a specified maximum size ($dmax$) to approximate the SVM primal cost function well; (3) it is efficient and roughly scales as $O(ndmax^2)$ where $n$ is the number of training examples; and, (4) the number of basis functions it requires to achieve an accuracy close to the SVM accuracy is usually far less than the number of SVM support vectors.

ei

PDF [BibTex]

PDF [BibTex]


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ARTS: Accurate Recognition of Transcription Starts in Human

Sonnenburg, S., Zien, A., Rätsch, G.

Bioinformatics, 22(14):e472-e480, July 2006 (article)

Abstract
Motivation: One of the most important features of genomic DNA are the protein-coding genes. While it is of great value to identify those genes and the encoded proteins, it is also crucial to understand how their transcription is regulated. To this end one has to identify the corresponding promoters and the contained transcription factor binding sites. TSS finders can be used to locate potential promoters. They may also be used in combination with other signal and content detectors to resolve entire gene structures. Results: We have developed a novel kernel based method - called ARTS - that accurately recognizes transcription start sites in human. The application of otherwise too computationally expensive Support Vector Machines was made possible due to the use of efficient training and evaluation techniques using suffix tries. In a carefully designed experimental study, we compare our TSS finder to state-of-the-art methods from the literature: McPromoter, Eponine and FirstEF. For given false positive rates within a reasonable range, we consistently achieve considerably higher true positive rates. For instance, ARTS finds about 24% true positives at a false positive rate of 1/1000, where the other methods find less than half (10.5%). Availability: Datasets, model selection results, whole genome predictions, and additional experimental results are available at http://www.fml.tuebingen.mpg.de/raetsch/projects/arts

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Large Scale Multiple Kernel Learning

Sonnenburg, S., Rätsch, G., Schäfer, C., Schölkopf, B.

Journal of Machine Learning Research, 7, pages: 1531-1565, July 2006 (article)

Abstract
While classical kernel-based learning algorithms are based on a single kernel, in practice it is often desirable to use multiple kernels. Lanckriet et al. (2004) considered conic combinations of kernel matrices for classification, leading to a convex quadratically constrained quadratic program. We show that it can be rewritten as a semi-infinite linear program that can be efficiently solved by recycling the standard SVM implementations. Moreover, we generalize the formulation and our method to a larger class of problems, including regression and one-class classification. Experimental results show that the proposed algorithm works for hundred thousands of examples or hundreds of kernels to be combined, and helps for automatic model selection, improving the interpretability of the learning result. In a second part we discuss general speed up mechanism for SVMs, especially when used with sparse feature maps as appear for string kernels, allowing us to train a string kernel SVM on a 10 million real-world splice data set from computational biology. We integrated multiple kernel learning in our machine learning toolbox SHOGUN for which the source code is publicly available at http://www.fml.tuebingen.mpg.de/raetsch/projects/shogun.

ei

PDF [BibTex]

PDF [BibTex]


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Factorial coding of natural images: how effective are linear models in removing higher-order dependencies?

Bethge, M.

Journal of the Optical Society of America A, 23(6):1253-1268, June 2006 (article)

Abstract
The performance of unsupervised learning models for natural images is evaluated quantitatively by means of information theory. We estimate the gain in statistical independence (the multi-information reduction) achieved with independent component analysis (ICA), principal component analysis (PCA), zero-phase whitening, and predictive coding. Predictive coding is translated into the transform coding framework, where it can be characterized by the constraint of a triangular filter matrix. A randomly sampled whitening basis and the Haar wavelet are included into the comparison as well. The comparison of all these methods is carried out for different patch sizes, ranging from 2x2 to 16x16 pixels. In spite of large differences in the shape of the basis functions, we find only small differences in the multi-information between all decorrelation transforms (5% or less) for all patch sizes. Among the second-order methods, PCA is optimal for small patch sizes and predictive coding performs best for large patch sizes. The extra gain achieved with ICA is always less than 2%. In conclusion, the `edge filters‘ found with ICA lead only to a surprisingly small improvement in terms of its actual objective.

ei

PDF Web [BibTex]

PDF Web [BibTex]


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Classifying EEG and ECoG Signals without Subject Training for Fast BCI Implementation: Comparison of Non-Paralysed and Completely Paralysed Subjects

Hill, N., Lal, T., Schröder, M., Hinterberger, T., Wilhelm, B., Nijboer, F., Mochty, U., Widman, G., Elger, C., Schölkopf, B., Kübler, A., Birbaumer, N.

IEEE Transactions on Neural Systems and Rehabilitation Engineering, 14(2):183-186, June 2006 (article)

Abstract
We summarize results from a series of related studies that aim to develop a motor-imagery-based brain-computer interface using a single recording session of EEG or ECoG signals for each subject. We apply the same experimental and analytical methods to 11 non-paralysed subjects (8 EEG, 3 ECoG), and to 5 paralysed subjects (4 EEG, 1 ECoG) who had been unable to communicate for some time. While it was relatively easy to obtain classifiable signals quickly from most of the non-paralysed subjects, it proved impossible to classify the signals obtained from the paralysed patients by the same methods. This highlights the fact that though certain BCI paradigms may work well with healthy subjects, this does not necessarily indicate success with the target user group. We outline possible reasons for this failure to transfer.

ei

PDF PDF DOI [BibTex]

PDF PDF DOI [BibTex]


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SCARNA: Fast and Accurate Structural Alignment of RNA Sequences by Matching Fixed-Length Stem Fragments

Tabei, Y., Tsuda, K., Kin, T., Asai, K.

Bioinformatics, 22(14):1723-1729, May 2006 (article)

Abstract
The functions of non-coding RNAs are strongly related to their secondary structures, but it is known that a secondary structure prediction of a single sequence is not reliable. Therefore, we have to collect similar RNA sequences with a common secondary structure for the analyses of a new non-coding RNA without knowing the exact secondary structure itself. Therefore, the sequence comparison in searching similar RNAs should consider not only their sequence similarities but their potential secondary structures. Sankoff‘s algorithm predicts the common secondary structures of the sequences, but it is computationally too expensive to apply to large-scale analyses. Because we often want to compare a large number of cDNA sequences or to search similar RNAs in the whole genome sequences, much faster algorithms are required. We propose a new method of comparing RNA sequences based on the structural alignments of the fixed-length fragments of the stem candidates. The implemented software, SCARNA (Stem Candidate Aligner for RNAs), is fast enough to apply to the long sequences in the large-scale analyses. The accuracy of the alignments is better or comparable to the much slower existing algorithms.

ei

PDF Web DOI [BibTex]


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The Effect of Artifacts on Dependence Measurement in fMRI

Gretton, A., Belitski, A., Murayama, Y., Schölkopf, B., Logothetis, N.

Magnetic Resonance Imaging, 24(4):401-409, April 2006 (article)

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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An Automated Combination of Sequence Motif Kernels for Predicting Protein Subcellular Localization

Zien, A., Ong, C.

(146), Max Planck Institute for Biological Cybernetics, Tübingen, April 2006 (techreport)

Abstract
Protein subcellular localization is a crucial ingredient to many important inferences about cellular processes, including prediction of protein function and protein interactions. While many predictive computational tools have been proposed, they tend to have complicated architectures and require many design decisions from the developer. We propose an elegant and fully automated approach to building a prediction system for protein subcellular localization. We propose a new class of protein sequence kernels which considers all motifs including motifs with gaps. This class of kernels allows the inclusion of pairwise amino acid distances into their computation. We further propose a multiclass support vector machine method which directly solves protein subcellular localization without resorting to the common approach of splitting the problem into several binary classification problems. To automatically search over families of possible amino acid motifs, we generalize our method to optimize over multiple kernels at the same time. We compare our automated approach to four other predictors on three different datasets.

ei

PDF Web [BibTex]

PDF Web [BibTex]


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Phase noise and the classification of natural images

Wichmann, F., Braun, D., Gegenfurtner, K.

Vision Research, 46(8-9):1520-1529, April 2006 (article)

Abstract
We measured the effect of global phase manipulations on a rapid animal categorization task. The Fourier spectra of our images of natural scenes were manipulated by adding zero-mean random phase noise at all spatial frequencies. The phase noise was the independent variable, uniformly and symmetrically distributed between 0 degree and ±180 degrees. Subjects were remarkably resistant to phase noise. Even with ±120 degree phase noise subjects were still performing at 75% correct. The high resistance of the subjects’ animal categorization rate to phase noise suggests that the visual system is highly robust to such random image changes. The proportion of correct answers closely followed the correlation between original and the phase noise-distorted images. Animal detection rate was higher when the same task was performed with contrast reduced versions of the same natural images, at contrasts where the contrast reduction mimicked that resulting from our phase randomization. Since the subjects’ categorization rate was better in the contrast experiment, reduction of local contrast alone cannot explain the performance in the phase noise experiment. This result obtained with natural images differs from those obtained for simple sinusoidal stimuli were performance changes due to phase changes are attributed to local contrast changes only. Thus the global phasechange accompanying disruption of image structure such as edges and object boundaries at different spatial scales reduces object classification over and above the performance deficit resulting from reducing contrast. Additional colour information improves the categorization performance by 2 %.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Training a Support Vector Machine in the Primal

Chapelle, O.

(147), Max Planck Institute for Biological Cybernetics, Tübingen, April 2006, The version in the "Large Scale Kernel Machines" book is more up to date. (techreport)

Abstract
Most literature on Support Vector Machines (SVMs) concentrate on the dual optimization problem. In this paper, we would like to point out that the primal problem can also be solved efficiently, both for linear and non-linear SVMs, and there is no reason for ignoring it. Moreover, from the primal point of view, new families of algorithms for large scale SVM training can be investigated.

ei

PDF [BibTex]

PDF [BibTex]


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A Direct Method for Building Sparse Kernel Learning Algorithms

Wu, M., Schölkopf, B., BakIr, G.

Journal of Machine Learning Research, 7, pages: 603-624, April 2006 (article)

Abstract
Many Kernel Learning Algorithms(KLA), including Support Vector Machine (SVM), result in a Kernel Machine (KM), such as a kernel classifier, whose key component is a weight vector in a feature space implicitly introduced by a positive definite kernel function. This weight vector is usually obtained by solving a convex optimization problem. Based on this fact we present a direct method to build Sparse Kernel Learning Algorithms (SKLA) by adding one more constraint to the original convex optimization problem, such that the sparseness of the resulting KM is explicitly controlled while at the same time the performance of the resulting KM can be kept as high as possible. A gradient based approach is provided to solve this modified optimization problem. Applying this method to the SVM results in a concrete algorithm for building Sparse Large Margin Classifiers (SLMC). Further analysis of the SLMC algorithm indicates that it essentially finds a discriminating subspace that can be spanned by a small number of vectors, and in this subspace, the different classes of data are linearly well separated. Experimental results over several classification benchmarks demonstrate the effectiveness of our approach.

ei

PDF PDF [BibTex]

PDF PDF [BibTex]


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Statistical Properties of Kernel Principal Component Analysis

Blanchard, G., Bousquet, O., Zwald, L.

Machine Learning, 66(2-3):259-294, March 2006 (article)

Abstract
We study the properties of the eigenvalues of Gram matrices in a non-asymptotic setting. Using local Rademacher averages, we provide data-dependent and tight bounds for their convergence towards eigenvalues of the corresponding kernel operator. We perform these computations in a functional analytic framework which allows to deal implicitly with reproducing kernel Hilbert spaces of infinite dimension. This can have applications to various kernel algorithms, such as Support Vector Machines (SVM). We focus on Kernel Principal Component Analysis (KPCA) and, using such techniques, we obtain sharp excess risk bounds for the reconstruction error. In these bounds, the dependence on the decay of the spectrum and on the closeness of successive eigenvalues is made explicit.

ei

PDF PDF DOI [BibTex]

PDF PDF DOI [BibTex]


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Network-based de-noising improves prediction from microarray data

Kato, T., Murata, Y., Miura, K., Asai, K., Horton, P., Tsuda, K., Fujibuchi, W.

BMC Bioinformatics, 7(Suppl. 1):S4-S4, March 2006 (article)

Abstract
Prediction of human cell response to anti-cancer drugs (compounds) from microarray data is a challenging problem, due to the noise properties of microarrays as well as the high variance of living cell responses to drugs. Hence there is a strong need for more practical and robust methods than standard methods for real-value prediction. We devised an extended version of the off-subspace noise-reduction (de-noising) method to incorporate heterogeneous network data such as sequence similarity or protein-protein interactions into a single framework. Using that method, we first de-noise the gene expression data for training and test data and also the drug-response data for training data. Then we predict the unknown responses of each drug from the de-noised input data. For ascertaining whether de-noising improves prediction or not, we carry out 12-fold cross-validation for assessment of the prediction performance. We use the Pearson‘s correlation coefficient between the true and predicted respon se values as the prediction performance. De-noising improves the prediction performance for 65% of drugs. Furthermore, we found that this noise reduction method is robust and effective even when a large amount of artificial noise is added to the input data. We found that our extended off-subspace noise-reduction method combining heterogeneous biological data is successful and quite useful to improve prediction of human cell cancer drug responses from microarray data.

ei

PDF PDF DOI [BibTex]

PDF PDF DOI [BibTex]


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Model-based Design Analysis and Yield Optimization

Pfingsten, T., Herrmann, D., Rasmussen, C.

IEEE Transactions on Semiconductor Manufacturing, 19(4):475-486, February 2006 (article)

Abstract
Fluctuations are inherent to any fabrication process. Integrated circuits and micro-electro-mechanical systems are particularly affected by these variations, and due to high quality requirements the effect on the devices’ performance has to be understood quantitatively. In recent years it has become possible to model the performance of such complex systems on the basis of design specifications, and model-based Sensitivity Analysis has made its way into industrial engineering. We show how an efficient Bayesian approach, using a Gaussian process prior, can replace the commonly used brute-force Monte Carlo scheme, making it possible to apply the analysis to computationally costly models. We introduce a number of global, statistically justified sensitivity measures for design analysis and optimization. Two models of integrated systems serve us as case studies to introduce the analysis and to assess its convergence properties. We show that the Bayesian Monte Carlo scheme can save costly simulation runs and can ensure a reliable accuracy of the analysis.

ei

PDF Web DOI [BibTex]

PDF Web DOI [BibTex]


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Weighting of experimental evidence in macromolecular structure determination

Habeck, M., Rieping, W., Nilges, M.

Proceedings of the National Academy of Sciences of the United States of America, 103(6):1756-1761, February 2006 (article)

Abstract
The determination of macromolecular structures requires weighting of experimental evidence relative to prior physical information. Although it can critically affect the quality of the calculated structures, experimental data are routinely weighted on an empirical basis. At present, cross-validation is the most rigorous method to determine the best weight. We describe a general method to adaptively weight experimental data in the course of structure calculation. It is further shown that the necessity to define weights for the data can be completely alleviated. We demonstrate the method on a structure calculation from NMR data and find that the resulting structures are optimal in terms of accuracy and structural quality. Our method is devoid of the bias imposed by an empirical choice of the weight and has some advantages over estimating the weight by cross-validation.

ei

Web DOI [BibTex]

Web DOI [BibTex]


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Cross-Validation Optimization for Structured Hessian Kernel Methods

Seeger, M., Chapelle, O.

Max-Planck Institute for Biological Cybernetics, Tübingen, Germany, February 2006 (techreport)

Abstract
We address the problem of learning hyperparameters in kernel methods for which the Hessian of the objective is structured. We propose an approximation to the cross-validation log likelihood whose gradient can be computed analytically, solving the hyperparameter learning problem efficiently through nonlinear optimization. Crucially, our learning method is based entirely on matrix-vector multiplication primitives with the kernel matrices and their derivatives, allowing straightforward specialization to new kernels or to large datasets. When applied to the problem of multi-way classification, our method scales linearly in the number of classes and gives rise to state-of-the-art results on a remote imaging task.

ei

PDF Web [BibTex]

PDF Web [BibTex]


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Classification of Faces in Man and Machine

Graf, A., Wichmann, F., Bülthoff, H., Schölkopf, B.

Neural Computation, 18(1):143-165, January 2006 (article)

ei

PDF Web [BibTex]

PDF Web [BibTex]

2003


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Support Vector Channel Selection in BCI

Lal, T., Schröder, M., Hinterberger, T., Weston, J., Bogdan, M., Birbaumer, N., Schölkopf, B.

(120), Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, December 2003 (techreport)

Abstract
Designing a Brain Computer Interface (BCI) system one can choose from a variety of features that may be useful for classifying brain activity during a mental task. For the special case of classifying EEG signals we propose the usage of the state of the art feature selection algorithms Recursive Feature Elimination [3] and Zero-Norm Optimization [13] which are based on the training of Support Vector Machines (SVM) [11]. These algorithms can provide more accurate solutions than standard filter methods for feature selection [14]. We adapt the methods for the purpose of selecting EEG channels. For a motor imagery paradigm we show that the number of used channels can be reduced significantly without increasing the classification error. The resulting best channels agree well with the expected underlying cortical activity patterns during the mental tasks. Furthermore we show how time dependent task specific information can be visualized.

ei

PDF Web [BibTex]

2003


PDF Web [BibTex]


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Concentration Inequalities for Sub-Additive Functions Using the Entropy Method

Bousquet, O.

Stochastic Inequalities and Applications, 56, pages: 213-247, Progress in Probability, (Editors: Giné, E., C. Houdré and D. Nualart), November 2003 (article)

Abstract
We obtain exponential concentration inequalities for sub-additive functions of independent random variables under weak conditions on the increments of those functions, like the existence of exponential moments for these increments. As a consequence of these general inequalities, we obtain refinements of Talagrand's inequality for empirical processes and new bounds for randomized empirical processes. These results are obtained by further developing the entropy method introduced by Ledoux.

ei

PostScript [BibTex]

PostScript [BibTex]


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Image Reconstruction by Linear Programming

Tsuda, K., Rätsch, G.

(118), Max Planck Institute for Biological Cybernetics, Tübingen, Germany, October 2003 (techreport)

ei

PDF [BibTex]

PDF [BibTex]


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Statistical Learning Theory, Capacity and Complexity

Schölkopf, B.

Complexity, 8(4):87-94, July 2003 (article)

Abstract
We give an exposition of the ideas of statistical learning theory, followed by a discussion of how a reinterpretation of the insights of learning theory could potentially also benefit our understanding of a certain notion of complexity.

ei

Web DOI [BibTex]


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Ranking on Data Manifolds

Zhou, D., Weston, J., Gretton, A., Bousquet, O., Schölkopf, B.

(113), Max Planck Institute for Biological Cybernetics, 72076 Tuebingen, Germany, June 2003 (techreport)

Abstract
The Google search engine has had a huge success with its PageRank web page ranking algorithm, which exploits global, rather than local, hyperlink structure of the World Wide Web using random walk. This algorithm can only be used for graph data, however. Here we propose a simple universal ranking algorithm for vectorial data, based on the exploration of the intrinsic global geometric structure revealed by a huge amount of data. Experimental results from image and text to bioinformatics illustrates the validity of our algorithm.

ei

PDF [BibTex]

PDF [BibTex]


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Kernel Hebbian Algorithm for Iterative Kernel Principal Component Analysis

Kim, K., Franz, M., Schölkopf, B.

(109), MPI f. biologische Kybernetik, Tuebingen, June 2003 (techreport)

Abstract
A new method for performing a kernel principal component analysis is proposed. By kernelizing the generalized Hebbian algorithm, one can iteratively estimate the principal components in a reproducing kernel Hilbert space with only linear order memory complexity. The derivation of the method, a convergence proof, and preliminary applications in image hyperresolution are presented. In addition, we discuss the extension of the method to the online learning of kernel principal components.

ei

PDF [BibTex]

PDF [BibTex]


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Learning with Local and Global Consistency

Zhou, D., Bousquet, O., Lal, T., Weston, J., Schölkopf, B.

(112), Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, June 2003 (techreport)

Abstract
We consider the learning problem in the transductive setting. Given a set of points of which only some are labeled, the goal is to predict the label of the unlabeled points. A principled clue to solve such a learning problem is the consistency assumption that a classifying function should be sufficiently smooth with respect to the structure revealed by these known labeled and unlabeled points. We present a simple algorithm to obtain such a smooth solution. Our method yields encouraging experimental results on a number of classification problems and demonstrates effective use of unlabeled data.

ei

[BibTex]

[BibTex]


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Dealing with large Diagonals in Kernel Matrices

Weston, J., Schölkopf, B., Eskin, E., Leslie, C., Noble, W.

Annals of the Institute of Statistical Mathematics, 55(2):391-408, June 2003 (article)

Abstract
In kernel methods, all the information about the training data is contained in the Gram matrix. If this matrix has large diagonal values, which arises for many types of kernels, then kernel methods do not perform well: We propose and test several methods for dealing with this problem by reducing the dynamic range of the matrix while preserving the positive definiteness of the Hessian of the quadratic programming problem that one has to solve when training a Support Vector Machine, which is a common kernel approach for pattern recognition.

ei

PDF DOI [BibTex]

PDF DOI [BibTex]


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Implicit Wiener Series

Franz, M., Schölkopf, B.

(114), Max Planck Institute for Biological Cybernetics, June 2003 (techreport)

Abstract
The Wiener series is one of the standard methods to systematically characterize the nonlinearity of a neural system. The classical estimation method of the expansion coefficients via cross-correlation suffers from severe problems that prevent its application to high-dimensional and strongly nonlinear systems. We propose a new estimation method based on regression in a reproducing kernel Hilbert space that overcomes these problems. Numerical experiments show performance advantages in terms of convergence, interpretability and system size that can be handled.

ei

PDF [BibTex]

PDF [BibTex]


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Machine Learning approaches to protein ranking: discriminative, semi-supervised, scalable algorithms

Weston, J., Leslie, C., Elisseeff, A., Noble, W.

(111), Max Planck Institute for Biological Cybernetics, Tübingen, Germany, June 2003 (techreport)

Abstract
A key tool in protein function discovery is the ability to rank databases of proteins given a query amino acid sequence. The most successful method so far is a web-based tool called PSI-BLAST which uses heuristic alignment of a profile built using the large unlabeled database. It has been shown that such use of global information via an unlabeled data improves over a local measure derived from a basic pairwise alignment such as performed by PSI-BLAST's predecessor, BLAST. In this article we look at ways of leveraging techniques from the field of machine learning for the problem of ranking. We show how clustering and semi-supervised learning techniques, which aim to capture global structure in data, can significantly improve over PSI-BLAST.

ei

PDF [BibTex]

PDF [BibTex]


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The em Algorithm for Kernel Matrix Completion with Auxiliary Data

Tsuda, K., Akaho, S., Asai, K.

Journal of Machine Learning Research, 4, pages: 67-81, May 2003 (article)

ei

PDF [BibTex]

PDF [BibTex]


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Constructing Descriptive and Discriminative Non-linear Features: Rayleigh Coefficients in Kernel Feature Spaces

Mika, S., Rätsch, G., Weston, J., Schölkopf, B., Smola, A., Müller, K.

IEEE Transactions on Pattern Analysis and Machine Intelligence, 25(5):623-628, May 2003 (article)

Abstract
We incorporate prior knowledge to construct nonlinear algorithms for invariant feature extraction and discrimination. Employing a unified framework in terms of a nonlinearized variant of the Rayleigh coefficient, we propose nonlinear generalizations of Fisher‘s discriminant and oriented PCA using support vector kernel functions. Extensive simulations show the utility of our approach.

ei

DOI [BibTex]

DOI [BibTex]


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The Geometry Of Kernel Canonical Correlation Analysis

Kuss, M., Graepel, T.

(108), Max Planck Institute for Biological Cybernetics, Tübingen, Germany, May 2003 (techreport)

Abstract
Canonical correlation analysis (CCA) is a classical multivariate method concerned with describing linear dependencies between sets of variables. After a short exposition of the linear sample CCA problem and its analytical solution, the article proceeds with a detailed characterization of its geometry. Projection operators are used to illustrate the relations between canonical vectors and variates. The article then addresses the problem of CCA between spaces spanned by objects mapped into kernel feature spaces. An exact solution for this kernel canonical correlation (KCCA) problem is derived from a geometric point of view. It shows that the expansion coefficients of the canonical vectors in their respective feature space can be found by linear CCA in the basis induced by kernel principal component analysis. The effect of mappings into higher dimensional feature spaces is considered critically since it simplifies the CCA problem in general. Then two regularized variants of KCCA are discussed. Relations to other methods are illustrated, e.g., multicategory kernel Fisher discriminant analysis, kernel principal component regression and possible applications thereof in blind source separation.

ei

PDF [BibTex]

PDF [BibTex]


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The Kernel Mutual Information

Gretton, A., Herbrich, R., Smola, A.

Max Planck Institute for Biological Cybernetics, April 2003 (techreport)

Abstract
We introduce two new functions, the kernel covariance (KC) and the kernel mutual information (KMI), to measure the degree of independence of several continuous random variables. The former is guaranteed to be zero if and only if the random variables are pairwise independent; the latter shares this property, and is in addition an approximate upper bound on the mutual information, as measured near independence, and is based on a kernel density estimate. We show that Bach and Jordan‘s kernel generalised variance (KGV) is also an upper bound on the same kernel density estimate, but is looser. Finally, we suggest that the addition of a regularising term in the KGV causes it to approach the KMI, which motivates the introduction of this regularisation. The performance of the KC and KMI is verified in the context of instantaneous independent component analysis (ICA), by recovering both artificial and real (musical) signals following linear mixing.

ei

PostScript [BibTex]

PostScript [BibTex]


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Tractable Inference for Probabilistic Data Models

Csato, L., Opper, M., Winther, O.

Complexity, 8(4):64-68, April 2003 (article)

Abstract
We present an approximation technique for probabilistic data models with a large number of hidden variables, based on ideas from statistical physics. We give examples for two nontrivial applications. © 2003 Wiley Periodicals, Inc.

ei

PDF GZIP Web [BibTex]

PDF GZIP Web [BibTex]


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Feature selection and transduction for prediction of molecular bioactivity for drug design

Weston, J., Perez-Cruz, F., Bousquet, O., Chapelle, O., Elisseeff, A., Schölkopf, B.

Bioinformatics, 19(6):764-771, April 2003 (article)

Abstract
Motivation: In drug discovery a key task is to identify characteristics that separate active (binding) compounds from inactive (non-binding) ones. An automated prediction system can help reduce resources necessary to carry out this task. Results: Two methods for prediction of molecular bioactivity for drug design are introduced and shown to perform well in a data set previously studied as part of the KDD (Knowledge Discovery and Data Mining) Cup 2001. The data is characterized by very few positive examples, a very large number of features (describing three-dimensional properties of the molecules) and rather different distributions between training and test data. Two techniques are introduced specifically to tackle these problems: a feature selection method for unbalanced data and a classifier which adapts to the distribution of the the unlabeled test data (a so-called transductive method). We show both techniques improve identification performance and in conjunction provide an improvement over using only one of the techniques. Our results suggest the importance of taking into account the characteristics in this data which may also be relevant in other problems of a similar type.

ei

Web [BibTex]


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Use of the Zero-Norm with Linear Models and Kernel Methods

Weston, J., Elisseeff, A., Schölkopf, B., Tipping, M.

Journal of Machine Learning Research, 3, pages: 1439-1461, March 2003 (article)

Abstract
We explore the use of the so-called zero-norm of the parameters of linear models in learning. Minimization of such a quantity has many uses in a machine learning context: for variable or feature selection, minimizing training error and ensuring sparsity in solutions. We derive a simple but practical method for achieving these goals and discuss its relationship to existing techniques of minimizing the zero-norm. The method boils down to implementing a simple modification of vanilla SVM, namely via an iterative multiplicative rescaling of the training data. Applications we investigate which aid our discussion include variable and feature selection on biological microarray data, and multicategory classification.

ei

PDF PostScript PDF [BibTex]

PDF PostScript PDF [BibTex]