5,156 research outputs found
Discriminative motif discovery in DNA and protein sequences using the DEME algorithm
<p>Abstract</p> <p>Background</p> <p>Motif discovery aims to detect short, highly conserved patterns in a collection of unaligned DNA or protein sequences. Discriminative motif finding algorithms aim to increase the sensitivity and selectivity of motif discovery by utilizing a second set of sequences, and searching only for patterns that can differentiate the two sets of sequences. Potential applications of discriminative motif discovery include discovering transcription factor binding site motifs in ChIP-chip data and finding protein motifs involved in thermal stability using sets of orthologous proteins from thermophilic and mesophilic organisms.</p> <p>Results</p> <p>We describe DEME, a discriminative motif discovery algorithm for use with protein and DNA sequences. Input to DEME is two sets of sequences; a "positive" set and a "negative" set. DEME represents motifs using a probabilistic model, and uses a novel combination of global and local search to find the motif that optimally discriminates between the two sets of sequences. DEME is unique among discriminative motif finders in that it uses an informative Bayesian prior on protein motif columns, allowing it to incorporate prior knowledge of residue characteristics. We also introduce four, synthetic, discriminative motif discovery problems that are designed for evaluating discriminative motif finders in various biologically motivated contexts. We test DEME using these synthetic problems and on two biological problems: finding yeast transcription factor binding motifs in ChIP-chip data, and finding motifs that discriminate between groups of thermophilic and mesophilic orthologous proteins.</p> <p>Conclusion</p> <p>Using artificial data, we show that DEME is more effective than a non-discriminative approach when there are "decoy" motifs or when a variant of the motif is present in the "negative" sequences. With real data, we show that DEME is as good, but not better than non-discriminative algorithms at discovering yeast transcription factor binding motifs. We also show that DEME can find highly informative thermal-stability protein motifs. Binaries for the stand-alone program DEME is free for academic use and is available at <url>http://bioinformatics.org.au/deme/</url></p
Contextual Motifs: Increasing the Utility of Motifs using Contextual Data
Motifs are a powerful tool for analyzing physiological waveform data.
Standard motif methods, however, ignore important contextual information (e.g.,
what the patient was doing at the time the data were collected). We hypothesize
that these additional contextual data could increase the utility of motifs.
Thus, we propose an extension to motifs, contextual motifs, that incorporates
context. Recognizing that, oftentimes, context may be unobserved or
unavailable, we focus on methods to jointly infer motifs and context. Applied
to both simulated and real physiological data, our proposed approach improves
upon existing motif methods in terms of the discriminative utility of the
discovered motifs. In particular, we discovered contextual motifs in continuous
glucose monitor (CGM) data collected from patients with type 1 diabetes.
Compared to their contextless counterparts, these contextual motifs led to
better predictions of hypo- and hyperglycemic events. Our results suggest that
even when inferred, context is useful in both a long- and short-term prediction
horizon when processing and interpreting physiological waveform data.Comment: 10 pages, 7 figures, accepted for oral presentation at KDD '1
Multiple instance learning for sequence data with across bag dependencies
In Multiple Instance Learning (MIL) problem for sequence data, the instances
inside the bags are sequences. In some real world applications such as
bioinformatics, comparing a random couple of sequences makes no sense. In fact,
each instance may have structural and/or functional relations with instances of
other bags. Thus, the classification task should take into account this across
bag relation. In this work, we present two novel MIL approaches for sequence
data classification named ABClass and ABSim. ABClass extracts motifs from
related instances and use them to encode sequences. A discriminative classifier
is then applied to compute a partial classification result for each set of
related sequences. ABSim uses a similarity measure to discriminate the related
instances and to compute a scores matrix. For both approaches, an aggregation
method is applied in order to generate the final classification result. We
applied both approaches to solve the problem of bacterial Ionizing Radiation
Resistance prediction. The experimental results of the presented approaches are
satisfactory
Feature-based time-series analysis
This work presents an introduction to feature-based time-series analysis. The
time series as a data type is first described, along with an overview of the
interdisciplinary time-series analysis literature. I then summarize the range
of feature-based representations for time series that have been developed to
aid interpretable insights into time-series structure. Particular emphasis is
given to emerging research that facilitates wide comparison of feature-based
representations that allow us to understand the properties of a time-series
dataset that make it suited to a particular feature-based representation or
analysis algorithm. The future of time-series analysis is likely to embrace
approaches that exploit machine learning methods to partially automate human
learning to aid understanding of the complex dynamical patterns in the time
series we measure from the world.Comment: 28 pages, 9 figure
Transcription Factor-DNA Binding Via Machine Learning Ensembles
We present ensemble methods in a machine learning (ML) framework combining
predictions from five known motif/binding site exploration algorithms. For a
given TF the ensemble starts with position weight matrices (PWM's) for the
motif, collected from the component algorithms. Using dimension reduction, we
identify significant PWM-based subspaces for analysis. Within each subspace a
machine classifier is built for identifying the TF's gene (promoter) targets
(Problem 1). These PWM-based subspaces form an ML-based sequence analysis tool.
Problem 2 (finding binding motifs) is solved by agglomerating k-mer (string)
feature PWM-based subspaces that stand out in identifying gene targets. We
approach Problem 3 (binding sites) with a novel machine learning approach that
uses promoter string features and ML importance scores in a classification
algorithm locating binding sites across the genome. For target gene
identification this method improves performance (measured by the F1 score) by
about 10 percentage points over the (a) motif scanning method and (b) the
coexpression-based association method. Top motif outperformed 5 component
algorithms as well as two other common algorithms (BEST and DEME). For
identifying individual binding sites on a benchmark cross species database
(Tompa et al., 2005) we match the best performer without much human
intervention. It also improved the performance on mammalian TFs.
The ensemble can integrate orthogonal information from different weak
learners (potentially using entirely different types of features) into a
machine learner that can perform consistently better for more TFs. The TF gene
target identification component (problem 1 above) is useful in constructing a
transcriptional regulatory network from known TF-target associations. The
ensemble is easily extendable to include more tools as well as future PWM-based
information.Comment: 33 page
Detecting Strong Ties Using Network Motifs
Detecting strong ties among users in social and information networks is a
fundamental operation that can improve performance on a multitude of
personalization and ranking tasks. Strong-tie edges are often readily obtained
from the social network as users often participate in multiple overlapping
networks via features such as following and messaging. These networks may vary
greatly in size, density and the information they carry. This setting leads to
a natural strong tie detection task: given a small set of labeled strong tie
edges, how well can one detect unlabeled strong ties in the remainder of the
network?
This task becomes particularly daunting for the Twitter network due to scant
availability of pairwise relationship attribute data, and sparsity of strong
tie networks such as phone contacts. Given these challenges, a natural approach
is to instead use structural network features for the task, produced by {\em
combining} the strong and "weak" edges. In this work, we demonstrate via
experiments on Twitter data that using only such structural network features is
sufficient for detecting strong ties with high precision. These structural
network features are obtained from the presence and frequency of small network
motifs on combined strong and weak ties. We observe that using motifs larger
than triads alleviate sparsity problems that arise for smaller motifs, both due
to increased combinatorial possibilities as well as benefiting strongly from
searching beyond the ego network. Empirically, we observe that not all motifs
are equally useful, and need to be carefully constructed from the combined
edges in order to be effective for strong tie detection. Finally, we reinforce
our experimental findings with providing theoretical justification that
suggests why incorporating these larger sized motifs as features could lead to
increased performance in planted graph models.Comment: To appear in Proceedings of WWW 2017 (Web-science track
Learning a Hybrid Architecture for Sequence Regression and Annotation
When learning a hidden Markov model (HMM), sequen- tial observations can
often be complemented by real-valued summary response variables generated from
the path of hid- den states. Such settings arise in numerous domains, includ-
ing many applications in biology, like motif discovery and genome annotation.
In this paper, we present a flexible frame- work for jointly modeling both
latent sequence features and the functional mapping that relates the summary
response variables to the hidden state sequence. The algorithm is com- patible
with a rich set of mapping functions. Results show that the availability of
additional continuous response vari- ables can simultaneously improve the
annotation of the se- quential observations and yield good prediction
performance in both synthetic data and real-world datasets.Comment: AAAI 201
Motif Discovery through Predictive Modeling of Gene Regulation
We present MEDUSA, an integrative method for learning motif models of
transcription factor binding sites by incorporating promoter sequence and gene
expression data. We use a modern large-margin machine learning approach, based
on boosting, to enable feature selection from the high-dimensional search space
of candidate binding sequences while avoiding overfitting. At each iteration of
the algorithm, MEDUSA builds a motif model whose presence in the promoter
region of a gene, coupled with activity of a regulator in an experiment, is
predictive of differential expression. In this way, we learn motifs that are
functional and predictive of regulatory response rather than motifs that are
simply overrepresented in promoter sequences. Moreover, MEDUSA produces a model
of the transcriptional control logic that can predict the expression of any
gene in the organism, given the sequence of the promoter region of the target
gene and the expression state of a set of known or putative transcription
factors and signaling molecules. Each motif model is either a -length
sequence, a dimer, or a PSSM that is built by agglomerative probabilistic
clustering of sequences with similar boosting loss. By applying MEDUSA to a set
of environmental stress response expression data in yeast, we learn motifs
whose ability to predict differential expression of target genes outperforms
motifs from the TRANSFAC dataset and from a previously published candidate set
of PSSMs. We also show that MEDUSA retrieves many experimentally confirmed
binding sites associated with environmental stress response from the
literature.Comment: RECOMB 200
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