647 research outputs found
Kernels for Protein Homology Detection
Determining protein sequence similarity is an important task for protein classification
and homology detection, which is typically performed using sequence
alignment algorithms. Fast and accurate alignment-free kernel based classifiers
exist, that treat protein sequences as a âbag of wordsâ. Kernels implicitly map
the sequences to a high dimensional feature space, and can be thought of as an
inner product between two vectors in that space. This allows an algorithm that
can be expressed purely in terms of inner products to be âkernelisedâ, where the
algorithm implicitly operates in the kernelâs feature space.
A weighted string kernel, where the weighting is derived using probabilistic methods,
is implemented using a binary data representation, and the results reported.
Alternative forms of data representation, such as Ising and frequency forms, are
implemented and the results discussed. These results are then used to inform the
development of a variety of novel kernels for protein sequence comparison.
Alternative forms of classifier are investigated, such as nearest neighbour, support
vector machines, and multiple kernel learning. A kernelized Gaussian classifier
is derived and tested, which is informative as it returns a score related to the
probability of a sequence belonging to a particular classification. Support vector
machines are tested with the introduced kernels, and the results compared to alternate
classifiers. As similarity can be thought of as having different components,
such as composition and position, multiple kernel learning is investigated with the
novel kernels developed here.
The results show that a support vector machine, using either single or multiple
kernels, is the best classifier for remote protein homology detection out of all the
classifiers tested in this thesis.EPSR
A Coverage Criterion for Spaced Seeds and its Applications to Support Vector Machine String Kernels and k-Mer Distances
Spaced seeds have been recently shown to not only detect more alignments, but
also to give a more accurate measure of phylogenetic distances (Boden et al.,
2013, Horwege et al., 2014, Leimeister et al., 2014), and to provide a lower
misclassification rate when used with Support Vector Machines (SVMs) (On-odera
and Shibuya, 2013), We confirm by independent experiments these two results,
and propose in this article to use a coverage criterion (Benson and Mak, 2008,
Martin, 2013, Martin and No{\'e}, 2014), to measure the seed efficiency in both
cases in order to design better seed patterns. We show first how this coverage
criterion can be directly measured by a full automaton-based approach. We then
illustrate how this criterion performs when compared with two other criteria
frequently used, namely the single-hit and multiple-hit criteria, through
correlation coefficients with the correct classification/the true distance. At
the end, for alignment-free distances, we propose an extension by adopting the
coverage criterion, show how it performs, and indicate how it can be
efficiently computed.Comment: http://online.liebertpub.com/doi/abs/10.1089/cmb.2014.017
Bounded Coordinate-Descent for Biological Sequence Classification in High Dimensional Predictor Space
We present a framework for discriminative sequence classification where the
learner works directly in the high dimensional predictor space of all
subsequences in the training set. This is possible by employing a new
coordinate-descent algorithm coupled with bounding the magnitude of the
gradient for selecting discriminative subsequences fast. We characterize the
loss functions for which our generic learning algorithm can be applied and
present concrete implementations for logistic regression (binomial
log-likelihood loss) and support vector machines (squared hinge loss).
Application of our algorithm to protein remote homology detection and remote
fold recognition results in performance comparable to that of state-of-the-art
methods (e.g., kernel support vector machines). Unlike state-of-the-art
classifiers, the resulting classification models are simply lists of weighted
discriminative subsequences and can thus be interpreted and related to the
biological problem
A Coverage Criterion for Spaced Seeds and its Applications to Support Vector Machine String Kernels and k-Mer Distances
Spaced seeds have been recently shown to not only detect more alignments, but
also to give a more accurate measure of phylogenetic distances (Boden et al.,
2013, Horwege et al., 2014, Leimeister et al., 2014), and to provide a lower
misclassification rate when used with Support Vector Machines (SVMs) (On-odera
and Shibuya, 2013), We confirm by independent experiments these two results,
and propose in this article to use a coverage criterion (Benson and Mak, 2008,
Martin, 2013, Martin and No{\'e}, 2014), to measure the seed efficiency in both
cases in order to design better seed patterns. We show first how this coverage
criterion can be directly measured by a full automaton-based approach. We then
illustrate how this criterion performs when compared with two other criteria
frequently used, namely the single-hit and multiple-hit criteria, through
correlation coefficients with the correct classification/the true distance. At
the end, for alignment-free distances, we propose an extension by adopting the
coverage criterion, show how it performs, and indicate how it can be
efficiently computed.Comment: http://online.liebertpub.com/doi/abs/10.1089/cmb.2014.017
A multi-species functional embedding integrating sequence and network structure
A key challenge to transferring knowledge between species is that different species have fundamentally different genetic architectures. Initial computational approaches to transfer knowledge across species have relied on measures of heredity such as genetic homology, but these approaches suffer from limitations. First, only a small subset of genes have homologs, limiting the amount of knowledge that can be transferred, and second, genes change or repurpose functions, complicating the transfer of knowledge. Many approaches address this problem by expanding the notion of homology by leveraging high-throughput genomic and proteomic measurements, such as through network alignment. In this work, we take a new approach to transferring knowledge across species by expanding the notion of homology through explicit measures of functional similarity between proteins in different species. Specifically, our kernel-based method, HANDL (Homology Assessment across Networks using Diffusion and Landmarks), integrates sequence and network structure to create a functional embedding in which proteins from different species are embedded in the same vector space. We show that inner products in this space and the vectors themselves capture functional similarity across species, and are useful for a variety of functional tasks. We perform the first whole-genome method for predicting phenologs, generating many that were previously identified, but also predicting new phenologs supported from the biological literature. We also demonstrate the HANDL embedding captures pairwise gene function, in that gene pairs with synthetic lethal interactions are significantly separated in HANDL space, and the direction of separation is conserved across species. Software for the HANDL algorithm is available at http://bit.ly/lrgr-handl.Published versio
Space-efficient Feature Maps for String Alignment Kernels
String kernels are attractive data analysis tools for analyzing string data.
Among them, alignment kernels are known for their high prediction accuracies in
string classifications when tested in combination with SVM in various
applications. However, alignment kernels have a crucial drawback in that they
scale poorly due to their quadratic computation complexity in the number of
input strings, which limits large-scale applications in practice. We address
this need by presenting the first approximation for string alignment kernels,
which we call space-efficient feature maps for edit distance with moves
(SFMEDM), by leveraging a metric embedding named edit sensitive parsing (ESP)
and feature maps (FMs) of random Fourier features (RFFs) for large-scale string
analyses. The original FMs for RFFs consume a huge amount of memory
proportional to the dimension d of input vectors and the dimension D of output
vectors, which prohibits its large-scale applications. We present novel
space-efficient feature maps (SFMs) of RFFs for a space reduction from O(dD) of
the original FMs to O(d) of SFMs with a theoretical guarantee with respect to
concentration bounds. We experimentally test SFMEDM on its ability to learn SVM
for large-scale string classifications with various massive string data, and we
demonstrate the superior performance of SFMEDM with respect to prediction
accuracy, scalability and computation efficiency.Comment: Full version for ICDM'19 pape
Kernel methods in genomics and computational biology
Support vector machines and kernel methods are increasingly popular in
genomics and computational biology, due to their good performance in real-world
applications and strong modularity that makes them suitable to a wide range of
problems, from the classification of tumors to the automatic annotation of
proteins. Their ability to work in high dimension, to process non-vectorial
data, and the natural framework they provide to integrate heterogeneous data
are particularly relevant to various problems arising in computational biology.
In this chapter we survey some of the most prominent applications published so
far, highlighting the particular developments in kernel methods triggered by
problems in biology, and mention a few promising research directions likely to
expand in the future
- âŠ