15147687
GAPWM: a genetic algorithm method for optimizing a position weight matrix
MOTIVATION
Position weight matrices (PMWs) are simple models commonly used in motif-finding algorithms to identify short functional elements, such as cis-regulatory motifs, on genes. When few experimentally verified motifs are available, estimation of the PWM may be poor. The resultant PWM may not reliably discriminate a true motif from a false one. While experimentally identifying such motifs remains time-consuming and expensive, low-resolution binding data from techniques such as ChIP-on-chip and ChIP-PET have become available. We propose a novel but simple method to improve a poorly estimated PWM using ChIP data.


METHODOLOGY
Starting from an existing PWM, a set of ChIP sequences, and a set of background sequences, our method, GAPWM, derives an improved PWM via a genetic algorithm that maximizes the area under the receiver operating characteristic (ROC) curve. GAPWM can easily incorporate prior information such as base conservation. We tested our method on two PMWs (Oct4/Sox2 and p53) using three recently published ChIP data sets (human Oct4, mouse Oct4 and human p53).


RESULTS
GAPWM substantially increased the sensitivity/specificity of a poorly estimated PWM and further improved the quality of a good PWM. Furthermore, it still functioned when the starting PWM contained a major error. The ROC performance of GAPWM compared favorably with that of MEME and others. With increasing availability of ChIP data, our method provides an alternative for obtaining high-quality PWMs for genome-wide identification of transcription factor binding sites.


AVAILABILITY
The C source code and all data used in this report are available at http://dir.niehs.nih.gov/dirbb/gapwm.


SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
26302874
Application of the GA/KNN method to SELDI proteomics data
SUMMARY
Proteomics technology has shown promise in identifying biomarkers for disease, toxicant exposure and stress. We show by example that the genetic algorithm/k-nearest neighbors method, developed for mining high-dimensional microarray gene expression data, is also capable of mining surface enhanced laser desorption/ionization-time-of-flight proteomics data.


AVAILABILITY
The source code of the program and documentation on how to use it are freely available to non-commercial users at http://dir.niehs.nih.gov/dirbb/lifiles/softlic.htm
15608177
Gene selection for sample classification based on gene expression data: study of sensitivity to choice of parameters of the GA/KNN method
MOTIVATION
We recently introduced a multivariate approach that selects a subset of predictive genes jointly for sample classification based on expression data. We tested the algorithm on colon and leukemia data sets. As an extension to our earlier work, we systematically examine the sensitivity, reproducibility and stability of gene selection/sample classification to the choice of parameters of the algorithm.


METHODS
Our approach combines a Genetic Algorithm (GA) and the k-Nearest Neighbor (KNN) method to identify genes that can jointly discriminate between different classes of samples (e.g. normal versus tumor). The GA/KNN method is a stochastic supervised pattern recognition method. The genes identified are subsequently used to classify independent test set samples.


RESULTS
The GA/KNN method is capable of selecting a subset of predictive genes from a large noisy data set for sample classification. It is a multivariate approach that can capture the correlated structure in the data. We find that for a given data set gene selection is highly repeatable in independent runs using the GA/KNN method. In general, however, gene selection may be less robust than classification.


AVAILABILITY
The method is available at http://dir.niehs.nih.gov/microarray/datamining


CONTACT
LI3@niehs.nih.gov
14498579
Accurate anchoring alignment of divergent sequences
MOTIVATION
Obtaining high quality alignments of divergent homologous sequences for cross-species sequence comparison remains a challenge.


RESULTS
We propose a novel pairwise sequence alignment algorithm, ACANA (ACcurate ANchoring Alignment), for aligning biological sequences at both local and global levels. Like many fast heuristic methods, ACANA uses an anchoring strategy. However, unlike others, ACANA uses a Smith-Waterman-like dynamic programming algorithm to recursively identify near-optimal regions as anchors for a global alignment. Performance evaluations using a simulated benchmark dataset and real promoter sequences suggest that ACANA is accurate and consistent, especially for divergent sequences. Specifically, we use a simulated benchmark dataset to show that ACANA has the highest sensitivity to align constrained functional sites compared to BLASTZ, CHAOS and DIALIGN for local alignment and compared to AVID, ClustalW, DIALIGN and LAGAN for global alignment. Applied to 6007 pairs of human-mouse orthologous promoter sequences, ACANA identified the largest number of conserved regions (defined as over 70% identity over 100 bp) compared to AVID, ClustalW, DIALIGN and LAGAN. In addition, the average length of conserved region identified by ACANA was the longest. Thus, we suggest that ACANA is a useful tool for identifying functional elements in cross-species sequence analysis, such as predicting transcription factor binding sites in non-coding DNA.


AVAILABILITY
ACANA software and test sequence data are publicly available at http://BioMedEmpire.org/
8071208
Incremental Model-based Learners With Formal Learning-Time Guarantees
Model-based learning algorithms have been shown to use experience efficiently when learning to solve Markov Decision Processes (MDPs) with finite state and action spaces. However, their high computational cost due to repeatedly solving an internal model inhibits their use in large-scale problems. We propose a method based on real-time dynamic programming (RTDP) to speed up two model-based algorithms, RMAX and MBIE (model-based interval estimation), resulting in computationally much faster algorithms with little loss compared to existing bounds. Specifically, our two new learning algorithms, RTDP-RMAX and RTDP-IE, have considerably smaller computational demands than RMAX and MBIE. We develop a general theoretical framework that allows us to prove that both are efficient learners in a PAC (probably approximately correct) sense. We also present an experimental evaluation of these new algorithms that helps quantify the tradeoff between computational and experience demands.
13836655
Dimension reduction methods for microarrays with application to censored survival data
MOTIVATION
Recent research has shown that gene expression profiles can potentially be used for predicting various clinical phenotypes, such as tumor class, drug response and survival time. While there has been extensive studies on tumor classification, there has been less emphasis on other phenotypic features, in particular, patient survival time or time to cancer recurrence, which are subject to right censoring. We consider in this paper an analysis of censored survival time based on microarray gene expression profiles.


RESULTS
We propose a dimension reduction strategy, which combines principal components analysis and sliced inverse regression, to identify linear combinations of genes, that both account for the variability in the gene expression levels and preserve the phenotypic information. The extracted gene combinations are then employed as covariates in a predictive survival model formulation. We apply the proposed method to a large diffuse large-B-cell lymphoma dataset, which consists of 240 patients and 7399 genes, and build a Cox proportional hazards model based on the derived gene expression components. The proposed method is shown to provide a good predictive performance for patient survival, as demonstrated by both the significant survival difference between the predicted risk groups and the receiver operator characteristics analysis.


AVAILABILITY
R programs are available upon request from the authors.


SUPPLEMENTARY INFORMATION
http://dna.ucdavis.edu/~hli/bioinfo-surv-supp.pdf.
3042580
A mixture model-based discriminate analysis for identifying ordered transcription factor binding site pairs in gene promoters directly regulated by estrogen receptor-alpha
MOTIVATION
To detect and select patterns of transcription factor binding sites (TFBSs) which distinguish genes directly regulated by estrogen receptor-alpha (ERalpha), we developed an innovative mixture model-based discriminate analysis for identifying ordered TFBS pairs.


RESULTS
Biologically, our proposed new algorithm clearly suggests that TFBSs are not randomly distributed within ERalpha target promoters (P-value < 0.001). The up-regulated targets significantly (P-value < 0.01) possess TFBS pairs, (DBP, MYC), (DBP, MYC/MAX heterodimer), (DBP, USF2) and (DBP, MYOGENIN); and down-regulated ERalpha target genes significantly (P-value < 0.01) possess TFBS pairs, such as (DBP, c-ETS1-68), (DBP, USF2) and (DBP, MYOGENIN). Statistically, our proposed mixture model-based discriminate analysis can simultaneously perform TFBS pattern recognition, TFBS pattern selection, and target class prediction; such integrative power cannot be achieved by current methods.


AVAILABILITY
The software is available on request from the authors.


CONTACT
lali@iupui.edu


SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
623541
A multiresolution volume rendering framework for large-scale time-varying data visualization
We present a new parallel multiresolution volume rendering framework for large-scale time-varying data visualization using the wavelet-based time-space partitioning (WTSP) tree. Utilizing the wavelet transform, a large-scale time-varying data set is converted into a space-time multiresolution data hierarchy, and is stored in a time-space partitioning (TSP) tree. To eliminate the parent-child data dependency for reconstruction and achieve load-balanced rendering, we design an algorithm to partition the WTSP tree and distribute the wavelet-compressed data along hierarchical space-filling curves with error-guided bucketization. At run time, the WTSP tree is traversed according to the user-specified time step and tolerances of both spatial and temporal errors. Data blocks of different spatio-temporal resolutions are reconstructed and rendered to compose the final image in parallel. We demonstrate that our algorithm can reduce the run-time communication cost to a minimum and ensure a well-balanced workload among processors when visualizing gigabytes of time-varying data on a PC cluster.
14580455
Supporting continuous consistency in multiplayer online games
Multiplayer online games have become very popular in recent years. However, they generally suffer from network latency problem. If a player changes its states, it will take some time before the changes are reflected to other concurrent players. This significantly affects the interactivity of the game. Sometimes, it may even cause disputes among the players. In this paper, we present a continuous consistency control mechanism to support collaborative game applications. Specifically, we propose a relaxed consistency control model for continuous events. Based on this model, we have developed a method to provide a global-wise continuous synchronization on the states of dynamic game objects presented among concurrent game players. We show the performance of the proposed method through some experiments.