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/
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
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
14467396
Image-based streamline generation and rendering
Seeding streamlines in 3D flow fields without considering their projections in screen space can produce visually cluttered rendering results. Streamlines will overlap or intersect with each other in the output image, which makes it difficult for the user to perceive the underlying flow structure. This paper presents a method to control the seeding and generation of streamlines in image space to avoid visual cluttering and allow a more flexible exploration of flow fields. In our algorithm, 2D images with depth maps generated by a variety of visualization techniques can be used as input from which seeds are placed and streamlines are generated. The density and rendering styles of streamlines can be flexibly controlled based on various criteria to improve visual clarity. With our image space approach, it is straightforward to implement the level of detail rendering, depth peeling, and stylized rendering of streamlines to allow for more effective visualization of 3D flow fields.
2365659
A Trajectory-Preserving Synchronization Method for Collaborative Visualization
In the past decade, a lot of research work has been conducted to support collaborative visualization among remote users over the networks, allowing them to visualize and manipulate shared data for problem solving. There are many applications of collaborative visualization, such as oceanography, meteorology and medical science. To facilitate user interaction, a critical system requirement for collaborative visualization is to ensure that remote users would perceive a synchronized view of the shared data. Failing this requirement, the user's ability in performing the desirable collaborative tasks would be affected. In this paper, we propose a synchronization method to support collaborative visualization. It considers how interaction with dynamic objects is perceived by application participants under the existence of network latency, and remedies the motion trajectory of the dynamic objects. It also handles the false positive and false negative collision detection problems. The new method is particularly well designed for handling content changes due to unpredictable user interventions or object collisions. We demonstrate the effectiveness of our method through a number of experiments
32462907
Alignment of Optical Maps
We introduce a new scoring method for calculation of alignments of optical maps. Missing cuts, false cuts, and sizing errors present in optical maps are addressed by our alignment score through calculation of corresponding likelihoods. The size error model is derived through the application of Central Limit Theorem and validated by residual plots collected from real data. Missing cuts and false cuts are modeled as Bernoulli and Poisson events, respectively, as suggested by previous studies. Likelihoods are used to derive an alignment score through calculation of likelihood ratios for a certain hypothesis test. This allows us to achieve maximal descriminative power for the alignment score. Our scoring method is naturally embedded within a well known DP framework for finding optimal alignments.
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.
11083681
MARD: a new method to detect differential gene expression in treatment-control time courses
MOTIVATION
Characterizing the dynamic regulation of gene expression by time course experiments is becoming more and more important. A common problem is to identify differentially expressed genes between the treatment and control time course. It is often difficult to compare expression patterns of a gene between two time courses for the following reasons: (1) the number of sampling time points may be different or hard to be aligned between the treatment and the control time courses; (2) estimation of the function that describes the expression of a gene in a time course is difficult and error-prone due to the limited number of time points. We propose a novel method to identify the differentially expressed genes between two time courses, which avoids direct comparison of gene expression patterns between the two time courses.


RESULTS
Instead of attempting to 'align' and compare the two time courses directly, we first convert the treatment and control time courses into neighborhood systems that reflect the underlying relationships between genes. We then identify the differentially expressed genes by comparing the two gene relationship networks. To verify our method, we apply it to two treatment-control time course datasets. The results are consistent with the previous results and also give some new biologically meaningful findings.


AVAILABILITY
The algorithm in this paper is coded in C++ and is available from http://leili-lab.cmb.usc.edu/yeastaging/projects/MARD/