1,484 research outputs found
Probabilistic Random Walk Models for Comparative Network Analysis
Graph-based systems and data analysis methods have become critical tools in many
fields as they can provide an intuitive way of representing and analyzing interactions between
variables. Due to the advances in measurement techniques, a massive amount of
labeled data that can be represented as nodes on a graph (or network) have been archived
in databases. Additionally, novel data without label information have been gradually generated
and archived. Labeling and identifying characteristics of novel data is an important
first step in utilizing the valuable data in an effective and meaningful way. Comparative
network analysis is an effective computational means to identify and predict the properties
of the unlabeled data by comparing the similarities and differences between well-studied
and less-studied networks. Comparative network analysis aims to identify the matching
nodes and conserved subnetworks across multiple networks to enable a prediction of the
properties of the nodes in the less-studied networks based on the properties of the matching
nodes in the well-studied networks (i.e., transferring knowledge between networks).
One of the fundamental and important questions in comparative network analysis is
how to accurately estimate node-to-node correspondence as it can be a critical clue in
analyzing the similarities and differences between networks. Node correspondence is a
comprehensive similarity that integrates various types of similarity measurements in a
balanced manner. However, there are several challenges in accurately estimating the node
correspondence for large-scale networks. First, the scale of the networks is a critical issue.
As networks generally include a large number of nodes, we have to examine an extremely
large space and it can pose a computational challenge due to the combinatorial nature of
the problem. Furthermore, although there are matching nodes and conserved subnetworks
in different networks, structural variations such as node insertions and deletions make it difficult to integrate a topological similarity.
In this dissertation, novel probabilistic random walk models are proposed to accurately
estimate node-to-node correspondence between networks. First, we propose a context-sensitive
random walk (CSRW) model. In the CSRW model, the random walker analyzes
the context of the current position of the random walker and it can switch the random
movement to either a simultaneous walk on both networks or an individual walk on one
of the networks. The context-sensitive nature of the random walker enables the method
to effectively integrate different types of similarities by dealing with structural variations.
Second, we propose the CUFID (Comparative network analysis Using the steady-state
network Flow to IDentify orthologous proteins) model. In the CUFID model, we construct
an integrated network by inserting pseudo edges between potential matching nodes in
different networks. Then, we design the random walk protocol to transit more frequently
between potential matching nodes as their node similarity increases and they have more
matching neighboring nodes. We apply the proposed random walk models to comparative
network analysis problems: global network alignment and network querying. Through
extensive performance evaluations, we demonstrate that the proposed random walk models
can accurately estimate node correspondence and these can lead to improved and reliable
network comparison results
Probabilistic Random Walk Models for Comparative Network Analysis
Graph-based systems and data analysis methods have become critical tools in many
fields as they can provide an intuitive way of representing and analyzing interactions between
variables. Due to the advances in measurement techniques, a massive amount of
labeled data that can be represented as nodes on a graph (or network) have been archived
in databases. Additionally, novel data without label information have been gradually generated
and archived. Labeling and identifying characteristics of novel data is an important
first step in utilizing the valuable data in an effective and meaningful way. Comparative
network analysis is an effective computational means to identify and predict the properties
of the unlabeled data by comparing the similarities and differences between well-studied
and less-studied networks. Comparative network analysis aims to identify the matching
nodes and conserved subnetworks across multiple networks to enable a prediction of the
properties of the nodes in the less-studied networks based on the properties of the matching
nodes in the well-studied networks (i.e., transferring knowledge between networks).
One of the fundamental and important questions in comparative network analysis is
how to accurately estimate node-to-node correspondence as it can be a critical clue in
analyzing the similarities and differences between networks. Node correspondence is a
comprehensive similarity that integrates various types of similarity measurements in a
balanced manner. However, there are several challenges in accurately estimating the node
correspondence for large-scale networks. First, the scale of the networks is a critical issue.
As networks generally include a large number of nodes, we have to examine an extremely
large space and it can pose a computational challenge due to the combinatorial nature of
the problem. Furthermore, although there are matching nodes and conserved subnetworks
in different networks, structural variations such as node insertions and deletions make it difficult to integrate a topological similarity.
In this dissertation, novel probabilistic random walk models are proposed to accurately
estimate node-to-node correspondence between networks. First, we propose a context-sensitive
random walk (CSRW) model. In the CSRW model, the random walker analyzes
the context of the current position of the random walker and it can switch the random
movement to either a simultaneous walk on both networks or an individual walk on one
of the networks. The context-sensitive nature of the random walker enables the method
to effectively integrate different types of similarities by dealing with structural variations.
Second, we propose the CUFID (Comparative network analysis Using the steady-state
network Flow to IDentify orthologous proteins) model. In the CUFID model, we construct
an integrated network by inserting pseudo edges between potential matching nodes in
different networks. Then, we design the random walk protocol to transit more frequently
between potential matching nodes as their node similarity increases and they have more
matching neighboring nodes. We apply the proposed random walk models to comparative
network analysis problems: global network alignment and network querying. Through
extensive performance evaluations, we demonstrate that the proposed random walk models
can accurately estimate node correspondence and these can lead to improved and reliable
network comparison results
Multi-omics integration accurately predicts cellular state in unexplored conditions for Escherichia coli.
A significant obstacle in training predictive cell models is the lack of integrated data sources. We develop semi-supervised normalization pipelines and perform experimental characterization (growth, transcriptional, proteome) to create Ecomics, a consistent, quality-controlled multi-omics compendium for Escherichia coli with cohesive meta-data information. We then use this resource to train a multi-scale model that integrates four omics layers to predict genome-wide concentrations and growth dynamics. The genetic and environmental ontology reconstructed from the omics data is substantially different and complementary to the genetic and chemical ontologies. The integration of different layers confers an incremental increase in the prediction performance, as does the information about the known gene regulatory and protein-protein interactions. The predictive performance of the model ranges from 0.54 to 0.87 for the various omics layers, which far exceeds various baselines. This work provides an integrative framework of omics-driven predictive modelling that is broadly applicable to guide biological discovery
Parallel Exchange of Randomized SubGraphs for Optimization of Network Alignment: PERSONA
The aim of Network Alignment in Protein-Protein Interaction Networks is discovering functionally similar regions between compared organisms. One major compromise for solving a network alignment problem is the trade-off among multiple similarity objectives while applying an alignment strategy. An alignment may lose its biological relevance while favoring certain objectives upon others due to the actual relevance of unfavored objectives. One possible solution for solving this issue may be blending the stronger aspects of various alignment strategies until achieving mature solutions. This study proposes a parallel approach called PERSONA that allows aligners to share their partial solutions continuously while they progress. All these aligners pursue their particular heuristics as part of a particle swarm that searches for multi-objective solutions of the same alignment problem in a reactive actor environment. The actors use the stronger portion of a solution as a subgraph that they receive from leading or other actors and send their own stronger subgraphs back upon evaluation of those partial solutions. Moreover, the individual heuristics of each actor takes randomized parameter values at each cycle of parallel execution so that the problem search space can thoroughly be investigated. The results achieved with PERSONA are remarkably optimized and balanced for both topological and node similarity objectives
Combining learning and constraints for genome-wide protein annotation
BackgroundThe advent of high-throughput experimental techniques paved the way to genome-wide computational analysis and predictive annotation studies. When considering the joint annotation of a large set of related entities, like all proteins of a certain genome, many candidate annotations could be inconsistent, or very unlikely, given the existing knowledge. A sound predictive framework capable of accounting for this type of constraints in making predictions could substantially contribute to the quality of machine-generated annotations at a genomic scale.ResultsWe present Ocelot, a predictive pipeline which simultaneously addresses functional and interaction annotation of all proteins of a given genome. The system combines sequence-based predictors for functional and protein-protein interaction (PPI) prediction with a consistency layer enforcing (soft) constraints as fuzzy logic rules. The enforced rules represent the available prior knowledge about the classification task, including taxonomic constraints over each GO hierarchy (e.g. a protein labeled with a GO term should also be labeled with all ancestor terms) as well as rules combining interaction and function prediction. An extensive experimental evaluation on the Yeast genome shows that the integration of prior knowledge via rules substantially improves the quality of the predictions. The system largely outperforms GoFDR, the only high-ranking system at the last CAFA challenge with a readily available implementation, when GoFDR is given access to intra-genome information only (as Ocelot), and has comparable or better results (depending on the hierarchy and performance measure) when GoFDR is allowed to use information from other genomes. Our system also compares favorably to recent methods based on deep learning
SANA: simulated annealing far outperforms many other search algorithms for biological network alignment
SummaryEvery alignment algorithm consists of two orthogonal components: an objective function M measuring the quality of an alignment, and a search algorithm that explores the space of alignments looking for ones scoring well according to M . We introduce a new search algorithm called SANA (Simulated Annealing Network Aligner) and apply it to protein-protein interaction networks using S 3 as the topological measure. Compared against 12 recent algorithms, SANA produces 5-10 times as many correct node pairings as the others when the correct answer is known. We expose an anti-correlation in many existing aligners between their ability to produce good topological vs. functional similarity scores, whereas SANA usually outscores other methods in both measures. If given the perfect objective function encoding the identity mapping, SANA quickly converges to the perfect solution while many other algorithms falter. We observe that when aligning networks with a known mapping and optimizing only S 3 , SANA creates alignments that are not perfect and yet whose S 3 scores match that of the perfect alignment. We call this phenomenon saturation of the topological score . Saturation implies that a measure's correlation with alignment correctness falters before the perfect alignment is reached. This, combined with SANA's ability to produce the perfect alignment if given the perfect objective function, suggests that better objective functions may lead to dramatically better alignments. We conclude that future work should focus on finding better objective functions, and offer SANA as the search algorithm of choice.Availability and implementationSoftware available at http://sana.ics.uci.edu [email protected] informationSupplementary data are available at Bioinformatics online
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