38,826 research outputs found
Towards Quantitative Classification of Folded Proteins in Terms of Elementary Functions
A comparative classification scheme provides a good basis for several
approaches to understand proteins, including prediction of relations between
their structure and biological function. But it remains a challenge to combine
a classification scheme that describes a protein starting from its well
organized secondary structures and often involves direct human involvement,
with an atomary level Physics based approach where a protein is fundamentally
nothing more than an ensemble of mutually interacting carbon, hydrogen, oxygen
and nitrogen atoms. In order to bridge these two complementary approaches to
proteins, conceptually novel tools need to be introduced. Here we explain how
the geometrical shape of entire folded proteins can be described analytically
in terms of a single explicit elementary function that is familiar from
nonlinear physical systems where it is known as the kink-soliton. Our approach
enables the conversion of hierarchical structural information into a
quantitative form that allows for a folded protein to be characterized in terms
of a small number of global parameters that are in principle computable from
atomary level considerations. As an example we describe in detail how the
native fold of the myoglobin 1M6C emerges from a combination of kink-solitons
with a very high atomary level accuracy. We also verify that our approach
describes longer loops and loops connecting -helices with
-strands, with same overall accuracy.Comment: 3 figure
A study of hierarchical and flat classification of proteins
Automatic classification of proteins using machine learning is an important problem that has received significant attention in the literature. One feature of this problem is that expert-defined hierarchies of protein classes exist and can potentially be exploited to improve classification performance. In this article we investigate empirically whether this is the case for two such hierarchies. We compare multi-class classification techniques that exploit the information in those class hierarchies and those that do not, using logistic regression, decision trees, bagged decision trees, and support vector machines as the underlying base learners. In particular, we compare hierarchical and flat variants of ensembles of nested dichotomies. The latter have been shown to deliver strong classification performance in multi-class settings. We present experimental results for synthetic, fold recognition, enzyme classification, and remote homology detection data. Our results show that exploiting the class hierarchy improves performance on the synthetic data, but not in the case of the protein classification problems. Based on this we recommend that strong flat multi-class methods be used as a baseline to establish the benefit of exploiting class hierarchies in this area
Seeing the Forest for the Trees: Using the Gene Ontology to Restructure Hierarchical Clustering
Motivation: There is a growing interest in improving the cluster analysis of expression data by incorporating into it prior knowledge, such as the Gene Ontology (GO) annotations of genes, in order to improve the biological relevance of the clusters that are subjected to subsequent scrutiny. The structure of the GO is another source of background knowledge that can be exploited through the use of semantic similarity. Results: We propose here a novel algorithm that integrates semantic similarities (derived from the ontology structure) into the procedure of deriving clusters from the dendrogram constructed during expression-based hierarchical clustering. Our approach can handle the multiple annotations, from different levels of the GO hierarchy, which most genes have. Moreover, it treats annotated and unannotated genes in a uniform manner. Consequently, the clusters obtained by our algorithm are characterized by significantly enriched annotations. In both cross-validation tests and when using an external index such as proteināprotein interactions, our algorithm performs better than previous approaches. When applied to human cancer expression data, our algorithm identifies, among others, clusters of genes related to immune response and glucose metabolism. These clusters are also supported by proteināprotein interaction data. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.Lynne and William Frankel Center for Computer Science; Paul Ivanier center for robotics research and production; National Institutes of Health (R01 HG003367-01A1
Nonlinear Models Using Dirichlet Process Mixtures
We introduce a new nonlinear model for classification, in which we model the
joint distribution of response variable, y, and covariates, x,
non-parametrically using Dirichlet process mixtures. We keep the relationship
between y and x linear within each component of the mixture. The overall
relationship becomes nonlinear if the mixture contains more than one component.
We use simulated data to compare the performance of this new approach to a
simple multinomial logit (MNL) model, an MNL model with quadratic terms, and a
decision tree model. We also evaluate our approach on a protein fold
classification problem, and find that our model provides substantial
improvement over previous methods, which were based on Neural Networks (NN) and
Support Vector Machines (SVM). Folding classes of protein have a hierarchical
structure. We extend our method to classification problems where a class
hierarchy is available. We find that using the prior information regarding the
hierarchical structure of protein folds can result in higher predictive
accuracy
DeepSF: deep convolutional neural network for mapping protein sequences to folds
Motivation
Protein fold recognition is an important problem in structural
bioinformatics. Almost all traditional fold recognition methods use sequence
(homology) comparison to indirectly predict the fold of a tar get protein based
on the fold of a template protein with known structure, which cannot explain
the relationship between sequence and fold. Only a few methods had been
developed to classify protein sequences into a small number of folds due to
methodological limitations, which are not generally useful in practice.
Results
We develop a deep 1D-convolution neural network (DeepSF) to directly classify
any protein se quence into one of 1195 known folds, which is useful for both
fold recognition and the study of se quence-structure relationship. Different
from traditional sequence alignment (comparison) based methods, our method
automatically extracts fold-related features from a protein sequence of any
length and map it to the fold space. We train and test our method on the
datasets curated from SCOP1.75, yielding a classification accuracy of 80.4%. On
the independent testing dataset curated from SCOP2.06, the classification
accuracy is 77.0%. We compare our method with a top profile profile alignment
method - HHSearch on hard template-based and template-free modeling targets of
CASP9-12 in terms of fold recognition accuracy. The accuracy of our method is
14.5%-29.1% higher than HHSearch on template-free modeling targets and
4.5%-16.7% higher on hard template-based modeling targets for top 1, 5, and 10
predicted folds. The hidden features extracted from sequence by our method is
robust against sequence mutation, insertion, deletion and truncation, and can
be used for other protein pattern recognition problems such as protein
clustering, comparison and ranking.Comment: 28 pages, 13 figure
Identification of functionally related enzymes by learning-to-rank methods
Enzyme sequences and structures are routinely used in the biological sciences
as queries to search for functionally related enzymes in online databases. To
this end, one usually departs from some notion of similarity, comparing two
enzymes by looking for correspondences in their sequences, structures or
surfaces. For a given query, the search operation results in a ranking of the
enzymes in the database, from very similar to dissimilar enzymes, while
information about the biological function of annotated database enzymes is
ignored.
In this work we show that rankings of that kind can be substantially improved
by applying kernel-based learning algorithms. This approach enables the
detection of statistical dependencies between similarities of the active cleft
and the biological function of annotated enzymes. This is in contrast to
search-based approaches, which do not take annotated training data into
account. Similarity measures based on the active cleft are known to outperform
sequence-based or structure-based measures under certain conditions. We
consider the Enzyme Commission (EC) classification hierarchy for obtaining
annotated enzymes during the training phase. The results of a set of sizeable
experiments indicate a consistent and significant improvement for a set of
similarity measures that exploit information about small cavities in the
surface of enzymes
Automated Protein Structure Classification: A Survey
Classification of proteins based on their structure provides a valuable
resource for studying protein structure, function and evolutionary
relationships. With the rapidly increasing number of known protein structures,
manual and semi-automatic classification is becoming ever more difficult and
prohibitively slow. Therefore, there is a growing need for automated, accurate
and efficient classification methods to generate classification databases or
increase the speed and accuracy of semi-automatic techniques. Recognizing this
need, several automated classification methods have been developed. In this
survey, we overview recent developments in this area. We classify different
methods based on their characteristics and compare their methodology, accuracy
and efficiency. We then present a few open problems and explain future
directions.Comment: 14 pages, Technical Report CSRG-589, University of Toront
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Integrative machine learning approach for multi-class SCOP protein fold classification
Classification and prediction of protein structure has been a central research theme in structural bioinformatics. Due to the imbalanced distribution of proteins over multi SCOP classification, most discriminative machine learning suffers the well-known āFalse Positives ā problem when learning over these types of problems. We have devised eKISS, an ensemble machine learning specifically designed to increase the coverage of positive examples when learning under multiclass imbalanced data sets. We have applied eKISS to classify 25 SCOP folds and show that our learning system improved over classical learning methods
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