Biomedical subjects

Jason Weston

Publications and source records attributed to Jason Weston.

9 recordsLinked to original sources

PubMed2006

Protein ranking by semi-supervised network propagation.

BACKGROUND: Biologists regularly search DNA or protein databases for sequences that share an evolutionary or functional relationship with a given query sequence. Traditional search methods, such as BLAST and PSI-BLAST, focus on detecting statistically significant pairwise sequence alignments and often miss more subtle sequence similarity. Recent work in the machine learning community has shown that exploiting the global structure of the network defined by these pairwise similarities can help detect more remote relationships than a purely local measure. METHODS: We review RankProp, a ranking algorithm that exploits the global network structure of similarity relationships among proteins in a database by performing a diffusion operation on a protein similarity network with weighted edges. The original RankProp algorithm is unsupervised. Here, we describe a semi-supervised version of the algorithm that uses labeled examples. Three possible ways of incorporating label information are considered: (i) as a validation set for model selection, (ii) to learn a new network, by choosing which transfer function to use for a given query, and (iii) to estimate edge weights, which measure the probability of inferring structural similarity. RESULTS: Benchmarked on a human-curated database of protein structures, the original RankProp algorithm provides significant improvement over local network search algorithms such as PSI-BLAST. Furthermore, we show here that labeled data can be used to learn a network without any need for estimating parameters of the transfer function, and that diffusion on this learned network produces better results than the original RankProp algorithm with a fixed network. CONCLUSION: In order to gain maximal information from a network, labeled and unlabeled data should be used to extract both local and global structure.

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PubMed2005

Motif-based protein ranking by network propagation.

MOTIVATION: Sequence similarity often suggests evolutionary relationships between protein sequences that can be important for inferring similarity of structure or function. The most widely-used pairwise sequence comparison algorithms for homology detection, such as BLAST and PSI-BLAST, often fail to detect less conserved remotely-related targets. RESULTS: In this paper, we propose a new general graph-based propagation algorithm called MotifProp to detect more subtle similarity relationships than pairwise comparison methods. MotifProp is based on a protein-motif network, in which edges connect proteins and the k-mer based motif features that they contain. We show that our new motif-based propagation algorithm can improve the ranking results over a base algorithm, such as PSI-BLAST, that is used to initialize the ranking. Despite the complex structure of the protein-motif network, MotifProp can be easily interpreted using the top-ranked motifs and motif-rich regions induced by the propagation, both of which are helpful for discovering conserved structural components in remote homologies.

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PubMed2005

Semi-supervised protein classification using cluster kernels.

MOTIVATION: Building an accurate protein classification system depends critically upon choosing a good representation of the input sequences of amino acids. Recent work using string kernels for protein data has achieved state-of-the-art classification performance. However, such representations are based only on labeled data--examples with known 3D structures, organized into structural classes--whereas in practice, unlabeled data are far more plentiful. RESULTS: In this work, we develop simple and scalable cluster kernel techniques for incorporating unlabeled data into the representation of protein sequences. We show that our methods greatly improve the classification performance of string kernels and outperform standard approaches for using unlabeled data, such as adding close homologs of the positive examples to the training data. We achieve equal or superior performance to previously presented cluster kernel methods and at the same time achieving far greater computational efficiency. AVAILABILITY: Source code is available at www.kyb.tuebingen.mpg.de/bs/people/weston/semiprot. The Spider matlab package is available at www.kyb.tuebingen.mpg.de/bs/people/spider. SUPPLEMENTARY INFORMATION: www.kyb.tuebingen.mpg.de/bs/people/weston/semiprot.

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PubMed2005

Identifying remote protein homologs by network propagation.

Perhaps the most widely used applications of bioinformatics are tools such as psi-blast for searching sequence databases. We describe a recently developed protein database search algorithm called rankprop. rankprop relies upon a precomputed network of pairwise protein similarities. The algorithm performs a diffusion operation from a specified query protein across the protein similarity network. The resulting activation scores, assigned to each database protein, encode information about the global structure of the protein similarity network. This type of algorithm has a rich history in associationist psychology, artificial intelligence and web search. We describe the rankprop algorithm and its relatives, and we provide evidence that the algorithm successfully improves upon the rankings produced by psi-blast.

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PubMed2004

Protein ranking: from local to global structure in the protein similarity network.

Biologists regularly search databases of DNA or protein sequences for evolutionary or functional relationships to a given query sequence. We describe a ranking algorithm that exploits the entire network structure of similarity relationships among proteins in a sequence database by performing a diffusion operation on a precomputed, weighted network. The resulting ranking algorithm, evaluated by using a human-curated database of protein structures, is efficient and provides significantly better rankings than a local network search algorithm such as psi-blast.

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PubMed2004

Mismatch string kernels for discriminative protein classification.

MOTIVATION: Classification of proteins sequences into functional and structural families based on sequence homology is a central problem in computational biology. Discriminative supervised machine learning approaches provide good performance, but simplicity and computational efficiency of training and prediction are also important concerns. RESULTS: We introduce a class of string kernels, called mismatch kernels, for use with support vector machines (SVMs) in a discriminative approach to the problem of protein classification and remote homology detection. These kernels measure sequence similarity based on shared occurrences of fixed-length patterns in the data, allowing for mutations between patterns. Thus, the kernels provide a biologically well-motivated way to compare protein sequences without relying on family-based generative models such as hidden Markov models. We compute the kernels efficiently using a mismatch tree data structure, allowing us to calculate the contributions of all patterns occurring in the data in one pass while traversing the tree. When used with an SVM, the kernels enable fast prediction on test sequences. We report experiments on two benchmark SCOP datasets, where we show that the mismatch kernel used with an SVM classifier performs competitively with state-of-the-art methods for homology detection, particularly when very few training examples are available. Examination of the highest-weighted patterns learned by the SVM classifier recovers biologically important motifs in protein families and superfamilies.

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PubMed2004

Support vector channel selection in BCI.

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 electroencephalogram (EEG) signals we propose the usage of the state of the art feature selection algorithms Recursive Feature Elimination and Zero-Norm Optimization which are based on the training of support vector machines (SVM). These algorithms can provide more accurate solutions than standard filter methods for feature selection. 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.

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PubMed2003

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

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.

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PubMed2002

Learning gene functional classifications from multiple data types.

In our attempts to understand cellular function at the molecular level, we must be able to synthesize information from disparate types of genomic data. We consider the problem of inferring gene functional classifications from a heterogeneous data set consisting of DNA microarray expression measurements and phylogenetic profiles from whole-genome sequence comparisons. We demonstrate the application of the support vector machine (SVM) learning algorithm to this functional inference task. Our results suggest the importance of exploiting prior information about the heterogeneity of the data. In particular, we propose an SVM kernel function that is explicitly heterogeneous. In addition, we describe feature scaling methods for further exploiting prior knowledge of heterogeneity by giving each data type different weights.

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