2269541
Principal component analysis for predicting transcription-factor binding motifs from array-derived data
BackgroundThe responses to interleukin 1 (IL-1) in human chondrocytes constitute a complex regulatory mechanism, where multiple transcription factors interact combinatorially to transcription-factor binding motifs (TFBMs). In order to select a critical set of TFBMs from genomic DNA information and an array-derived data, an efficient algorithm to solve a combinatorial optimization problem is required. Although computational approaches based on evolutionary algorithms are commonly employed, an analytical algorithm would be useful to predict TFBMs at nearly no computational cost and evaluate varying modelling conditions. Singular value decomposition (SVD) is a powerful method to derive primary components of a given matrix. Applying SVD to a promoter matrix defined from regulatory DNA sequences, we derived a novel method to predict the critical set of TFBMs.ResultsThe promoter matrix was defined to establish a quantitative relationship between the IL-1-driven mRNA alteration and genomic DNA sequences of the IL-1 responsive genes. The matrix was decomposed with SVD, and the effects of 8 potential TFBMs (5'-CAGGC-3', 5'-CGCCC-3', 5'-CCGCC-3', 5'-ATGGG-3', 5'-GGGAA-3', 5'-CGTCC-3', 5'-AAAGG-3', and 5'-ACCCA-3') were predicted from a pool of 512 random DNA sequences. The prediction included matches to the core binding motifs of biologically known TFBMs such as AP2, SP1, EGR1, KROX, GC-BOX, ABI4, ETF, E2F, SRF, STAT, IK-1, PPARγ, STAF, ROAZ, and NFκB, and their significance was evaluated numerically using Monte Carlo simulation and genetic algorithm.ConclusionThe described SVD-based prediction is an analytical method to provide a set of potential TFBMs involved in transcriptional regulation. The results would be useful to evaluate analytically a contribution of individual DNA sequences.
15270290
Modeling Transcriptional Regulation in Chondrogenesis Using Particle Swarm Optimization
Chondrogenesis is a complex developmental process involving many transcription factors. Using mRNA expression data and regulatory DNA sequences, we formulated a quantitative model to predict a set of transcription-factor binding motifs (TFBMs) as a combinatorial problem. To solve such a problem, an efficient computational algorithm should be employed. In the current study, particle swarm optimization was applied. Swarm intelligence is an artificial intelligence approach that mimics a behavior of swarm-forming agents. Such systems are made up with a population of individuals that interact locally and globally. Here, a group of TFBMs was predicted using 200 artificial bees and the results were compared to biologically known binding motifs.
17725399
Regulating gene expression using optimal control theory
We described development of a novel genome-based model-driven strategy useful for regulating eukaryotic gene expression. In order to extract biologically meaningful information from a large volume of mRNA expression data, we built previously a PROmoter-Based Estimation (PROBE) model. The PROBE model allowed us to establish a quantitative relationship between transcription-factor binding motifs in regulatory DNA sequences and mRNA expression levels. Here, we extended PROBE formulation to derive an optimal control law for gene regulation. The responses to shear stress in human synovial cells were chosen as a model biological system, and the system dynamics was identified from the expression pattern of the genes involved in degradation and maintenance of extracellular matrix. In order to suppress the responses to mechanical stimuli, a Ricatti equation was solved and an admissible control law was derived. The approach presented here can be implemented in any biological process, and it would be useful to develop a transcription-mediated strategy for gene therapies and tissue engineering.
39241507
Feature selection using a proximity-index optimization model
Abstract One of the recurring issues in pattern recognition problems has been feature extraction and selection. This paper addresses this issue from a different pespective. Without assuming any particular classificaiton algorithm, it first suggests that one extract as much information as conveniently possible in several pattern-information domains. This paper later suggests applying the proposed Proximity-Index method, to select a significantly smaller, yet optimal feature subset. This method is formally described and is successfully applied to a waveform classification problem. The features selected by the algorithm are used to classify ten signal classes and produce a very encouraging recognition performance of 87.00% on 200 samples. This method is computationally inexpensive and particularly useful for large data set problems.
12060317
DiCAS: An Efficient Distributed Caching Mechanism for P2P Systems
Peer-to-peer networks are widely criticized for their inefficient flooding search mechanism. Distributed hash table (DHT) algorithms have been proposed to improve the search efficiency by mapping the index of a file to a unique peer based on predefined hash functions. However, the tight coupling between indices and hosting peers incurs high maintenance cost in a highly dynamic network. To properly balance the tradeoff between the costs of indexing and searching, we propose the distributed caching and adaptive search (DiCAS) algorithm, where indices are passively cached in a group of peers based on a predefined hash function. Guided by the same function, adaptive search selectively forwards queries to "matched" peers with a high probability of caching the desired indices. The search cost is reduced due to shrunk searching space. Different from the DHT solutions, distributed caching loosely maps the index of a file to a group of peers in a passive fashion, which saves the cost of updating indices. Our simulation study shows that the DiCAS protocol can significantly reduce the network search traffic with the help of small cache space contributed by each individual peer
11940833
Efficient trust management policy analysis from rules
This paper describes a systematic method for deriving efficient algorithms and precise time complexities from extended Datalog rules as it is applied to the analysis of trust management policies specified in SPKI/SDSI, a well-known trust management framework designed to facilitate the development of secure and scalable distributed computing systems. The approach of expressing policy analysis problems as extended Datalog rules is much simpler than previous techniques for analysis of SPKI/SDSI policies. Our method also derives better, more precise time complexities than before in addition to generating complete algorithms and data structures. The method is general, with many applications beyond policy analysis. It extends our previous method for Datalog to handle list constructors, external functions, and queries.
18963770
A quasi-Monte Carlo method for computing areas of point-sampled surfaces
A novel and efficient quasi-Monte Carlo method for computing the area of a point-sampled surface with associated surface normal for each point is presented. Our method operates directly on the point cloud without any surface reconstruction procedure. Using the Cauchy-Crofton formula, the area of the point-sampled surface is calculated by counting the number of intersection points between the point cloud and a set of uniformly distributed lines generated with low-discrepancy sequences. Based on a clustering technique, we also propose an effective algorithm for computing the intersection points of a line with the point-sampled surface. By testing on a number of point-based models, experiments suggest that our method is more robust and more efficient than those conventional approaches based on surface reconstruction.
14931870
SVM decision boundary based discriminative subspace induction
We study the problem of linear dimension reduction for classification, with a focus on sufficient dimension reduction, i.e., finding subspaces without loss of discrimination power. First, we formulate the concept of sufficient subspace for classification in parallel terms as for regression. Then we present a new method to estimate the smallest sufficient subspace based on an improvement of decision boundary analysis (DBA). The main idea is to combine DBA with support vector machines (SVM) to overcome the inherent difficulty of DBA in small sample size situations while keeping DBA's estimation simplicity. The compact representation of SVM boundary results in a significant gain in both speed and accuracy over previous DBA implementations. Alternatively, this technique can be viewed as a way to reduce the run-time complexity of SVM itself. Comparative experiments on one simulated and four real-world benchmark datasets highlight the superior performance of the proposed approach.