Search PubMed⌕ Search

Biomedical subjects

Sören Sonnenburg

Publications and source records attributed to Sören Sonnenburg.

4 recordsLinked to original sources

ARTS: accurate recognition of transcription starts in human.

UNLABELLED: We develop new methods for finding transcription start sites (TSS) of RNA Polymerase II binding genes in genomic DNA sequences. Employing Support Vector Machines with advanced sequence kernels, we achieve drastically higher prediction accuracies than state-of-the-art methods. 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 35% true positives at a false positive rate of 1/1000, where the other methods find about a half (18%). AVAILABILITY: Datasets, model selection results, whole genome predictions, and additional experimental results are available at http://www.fml.tuebingen.mpg.de/raetsch/projects/arts.

Algorithms↗

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.

Algorithms↗

A new discriminative kernel from probabilistic models.

Recently, Jaakkola and Haussler (1999) proposed a method for constructing kernel functions from probabilistic models. Their so-called Fisher kernel has been combined with discriminative classifiers such as support vector machines and applied successfully in, for example, DNA and protein analysis. Whereas the Fisher kernel is calculated from the marginal log-likelihood, we propose the TOP kernel derived; from tangent vectors of posterior log-odds. Furthermore, we develop a theoretical framework on feature extractors from probabilistic models and use it for analyzing the TOP kernel. In experiments, our new discriminative TOP kernel compares favorably to the Fisher kernel.

Models, Neurological↗

Classifying 'drug-likeness' with kernel-based learning methods.

In this article we report about a successful application of modern machine learning technology, namely Support Vector Machines, to the problem of assessing the 'drug-likeness' of a chemical from a given set of descriptors of the substance. We were able to drastically improve the recent result by Byvatov et al. (2003) on this task and achieved an error rate of about 7% on unseen compounds using Support Vector Machines. We see a very high potential of such machine learning techniques for a variety of computational chemistry problems that occur in the drug discovery and drug design process.

Artificial Intelligence↗