52802682
Inferring domain-domain interactions from protein-protein interactions
Protein-protein interactions are important events in cellular and biochemical processes within a cell. Several researchers have undertaken the task of analyzing protein-protein interactions covering all genes of an organism by using yeast two-hybrid assays. Protein-protein interactions involve physical interactions between protein domains. Therefore, understanding protein interactions at the domain level gives a global view of the protein interaction network, and possibly extends functions of proteins. In this study, we present a Maximum Likelihood approach to infer domain-domain interactions from the 5719 yeast protein-protein interactions obtained in the high throughput two-hybrid experiments by Uetz et al., 2000 and Ito et al., 2001. The accuracies of our predictions are measured at the protein level. Our study includes the following three results: (1) using the inferred domain-domain interactions, we predict interactions between proteins and achieve 39.0% specificity and 79.7% sensitivity; (2) our predicted protein-protein interactions have a significant overlap with the MIPS(http://mips.gfs.de) protein-protein interactions obtained by methods other than the two-hybrid systems; and (3) the mean correlation coefficient of the gene expression profiles for our predicted interacting pairs is significantly higher than that for random pairs as well as that of interacting pairs in Uetz's and Ito's experimental data. Our method has shown robustness in analyzing incomplete data sets and dealing with various experimental errors. We find several novel protein-protein interactions such as RPS0A interacting with APG17 and TAF40 interacting with SPT3, which are consistent with the functions of the proteins.
5909245
Modeling Gene Expression with Differential Equations
We propose a differential equation model for gene expression and provide two methods to construct the model from a set of temporal data. We model both transcription and translation by kinetic equations with feedback loops from translation products to transcription. Degradation of proteins and mRNAs is also incorporated. We study two methods to construct the model from experimental data: Minimum Weight Solutions to Linear Equations (MWSLE), which determines the regulation by solving under-determined linear equations, and Fourier Transform for Stable Systems (FTSS), which refines the model with cell cycle constraints. The results suggest that a minor set of temporal data may be sufficient to construct the model at the genome level. We also give a comprehensive discussion of other extended models: the RNA Model, the Protein Model, and the Time Delay Model.
2057857
Gene-finding via tandem mass spectrometry
We propose a new gene-finding methodology that combines high performance liquid chromatograph (HPLC)-tandem mass spectrometry experiments with a fast computer algorithm to locate coding regions and introns. Proteins are first extracted from cells and digested by enzymes, and then the resulting peptides are separated and analyzed by HPLC-tandem mass spectrometry. We designed an algorithm to find DNA coding sequences, corresponding to open reading frames (ORF), in the genome such that their translated amino acid sequences are optimally correlated with these tandem mass spectra. In this algorithm, we also allow one gap, corresponding to an intron, between two DNA coding sequences, such that their concatenation becomes one coding sequence. Finally, the algorithm assembles these candidate coding sequences and introns into gene structures. Our algorithm was implemented to predict genes on 4 contigs with a total of 123 kbps using two sets of simulated digestion- HPLC-tandem mass spectrometry data of 2523 Caenorhabditis elegans Chromosome IV proteins, digested by trypsin and Asp-N respectively. Among 15 annotated genes in the forward strand, all 98 exons are hit by the predicted no-gap coding sequences, and 60 out of 83 introns are correctly predicted. We also tested gene structure prediction in a contig containing 3 genes. Combining splicing site predictions with predicted coding sequences and introns, we found all 3 gene structures.
11068219
An approximation algorithm for haplotype inference by maximum parsimony
This paper studies haplotype inference by maximum parsimony using population data. We define the optimal haplotype inference (OHI) problem as given a set of genotypes and a set of related haplotypes, find a minimum subset of haplotypes that can resolve all the genotypes. We prove that OHI is NP-hard and can be formulated as an integer quadratic programming (IQP) problem. To solve the IQP problem, we propose an iterative semi-definite programming based approximation algorithm, (called SDPHapInfer). We show that this algorithm finds a solution within a factor of O(logn) of the optimal solution, where n is the number of genotypes. This algorithm has been implemented and tested on a variety of simulated and biological data. In comparison with three other methods: HAPAR, HAPLOTYPER, and PHASE, the experimental results indicate that SDPHapInfer and HAPLOTYPER have similar error rates. In addition, the results generated by PHASE have lower error rates on some data but higher error rates on others. The error rates of HAPAR are higher than the others on biological data. In terms of efficiency, SDPHapInfer, HAPLOTYPER, and PHASE output a solution in a stable and consistent way, and they run much faster than HAPAR when the number of genotypes becomes large.
17774823
Scalable Partitioning and Exploration of Chemical Spaces Using Geometric Hashing
Virtual screening (VS) has become a preferred tool to augment high-throughput screening(1) and determine new leads in the drug discovery process. The core of a VS informatics pipeline includes several data mining algorithms that work on huge databases of chemical compounds containing millions of molecular structures and their associated data. Thus, scaling traditional applications such as classification, partitioning, and outlier detection for huge chemical data sets without a significant loss in accuracy is very important. In this paper, we introduce a data mining framework built on top of a recently developed fast approximate nearest-neighbor-finding algorithm(2) called locality-sensitive hashing (LSH) that can be used to mine huge chemical spaces in a scalable fashion using very modest computational resources. The core LSH algorithm hashes chemical descriptors so that points close to each other in the descriptor space are also close to each other in the hashed space. Using this data structure, one can perform approximate nearest-neighbor searches very quickly, in sublinear time. We validate the accuracy and performance of our framework on three real data sets of sizes ranging from 4337 to 249 071 molecules. Results indicate that the identification of nearest neighbors using the LSH algorithm is at least 2 orders of magnitude faster than the traditional k-nearest-neighbor method and is over 94% accurate for most query parameters. Furthermore, when viewed as a data-partitioning procedure, the LSH algorithm lends itself to easy parallelization of nearest-neighbor classification or regression. We also apply our framework to detect outlying (diverse) compounds in a given chemical space; this algorithm is extremely rapid in determining whether a compound is located in a sparse region of chemical space or not, and it is quite accurate when compared to results obtained using principal-component-analysis-based heuristics.
2083478
An integrative approach for causal gene identification and gene regulatory pathway inference
MOTIVATION
Gene expression variation can often be linked to certain chromosomal regions and are tightly associated with phenotypic variation such as disease conditions. Inferring the causal genes for the expression variation is of great importance but rather challenging as the linked region generally contains multiple genes. Even when a single candidate gene is proposed, the underlying biological mechanism by which the regulation is enforced remains unknown. Novel approaches are needed to both infer the causal genes and generate hypothesis on the underlying regulatory mechanisms.


RESULTS
We propose a new approach which aims at achieving the above objectives by integrating genotype information, gene expression, protein-protein interaction, protein phosphorylation, and transcription factor (TF)-DNA binding information. A network based stochastic algorithm is designed to infer the causal genes and identify the underlying regulatory pathways. We first quantitatively verified our method by a test using data generated by yeast knock-out experiments. Over 40% of inferred causal genes are correct, which is significantly better than 10% by random guess. We then applied our method to a recent genome-wide expression variation study in yeast. We show that our method can correctly identify the causal genes and effectively output experimentally verified pathways. New potential gene regulatory pathways are generated and presented as a global network.


AVAILABILITY
Source code is available upon request.
17432425
Structure analysis for dynamic software architecture
The open and dynamic Internet environment greatly urges software entities that are distributed on different locations to coordinate with each other to accomplish a computing task. Software architecture is applied to abstract the software entities to be components and the coordination between them to be connectors and then a model is extracted as the architecture on which the design, analysis and verification are based. Currently, the notion of dynamic software architectures that can modify their architecture and enact modifications during the system execution has become one of the most active research areas. In this paper, we focus on the dynamic evolution of system structure other than coordination mechanisms (e.g. communication protocols). It is widely recognized that some restrictions should be imposed on the system evolution to ensure that the system structure may remain one style or transform within a scope. These conditions, to a large extent, make the system execute under control as expected.
41663574
Mining Frequent Tree-Like Patterns in Large Datasets
In this paper, we propose a novel data mining scheme to explore the frequent hierarchical structure patterns, named tree-like patterns, with the relationship of each item on a sequence. By tree-like patterns, we are clear to find out the relation of items between the cause and effect. Finally, we discuss the different characteristics to our mined patterns with others. As a consequence, we can find out that our addressed tree-like patterns can be widely used to explore a variety of different applications.
17692093
Life after Video Coding Standards: Rate Shaping and Error Concealment
Is there life after video coding standards? One might think that research has no room to advance with the video coding standards already defined. On the contrary, exciting research opportunities arise after the standards are specified. In this paper, we introduce two standard-related research areas: rate shaping and error concealment, as examples of interesting research that finds its context in standards. Experiment results are also shown.
4650146
A New Coarse-to-Fine Framework for 3D Brain MR Image Registration
Registration, that is, the alignment of multiple images, has been one of the most challenging problems in the field of computer vision. It also serves as an important role in biomedical image analysis and its applications. Although various methods have been proposed for solving different kinds of registration problems in computer vision, the results are still far from ideal when it comes to real world biomedical image applications. For instance, in order to register 3D brain MR images, current state of the art registration methods use a multi-resolution coarse-to-fine algorithm, which typically involves starting with low resolution images and working progressively through to higher resolutions, with the aim to avoid the local maximum "traps". However, these methods do not always successfully avoid the local maximum. Consequently, various rather sophisticated optimization methods are developed to attack this problem. In this paper, we propose a novel viewpoint on the coarse-to-fine registration, in which coarse and fine images are distinguished by different scales of the objects instead of different resolutions of the images. Based on this new perspective, we develop a new image registration framework by combining the multi-resolution method with novel multi-scale algorithm, which could achieve higher accuracy and robustness on 3D brain MR images. We believe this work has great contribution to biomedical image analysis and related applications.
12569733
Modern floorplanning based on fast simulated annealing
Unlike classical floorplanning that usually handles only block packing to minimize silicon area, modern VLSI floorplanning typically needs to pack blocks within a fixed die (outline) and additionally considers the packing with block positions and interconnect constraints. Floorplanning with bus planning is one of the most challenging modern floorplanning problems because it needs to consider the constraints with interconnect and block positions simultaneously. We study in this paper two types of modern floorplanning problems: (1) fixed-outline floorplanning and (2) bus-driven floorplanning. Our floorplanner uses the B*-tree floorplan representation and is based on a fast three-stage simulated annealing scheme, called Fast-SA. For fixed-outline floorplanning, we present an adaptive Fast-SA that can dynamically change the weights in the cost function to optimize wirelength under the outline constraint. Experimental results show that our floorplanner can achieve almost 100% success rates efficiently for fixed-outline floorplanning with various aspect ratios, compared to 10%--90% success rates obtained by the most recent works. For the bus-driven floorplanning, we explore the feasibility conditions of the B*-tree with the bus constraints and develop a bus-driven floorplanning algorithm based on the conditions and Fast-SA. Experimental results show that our floorplanner on the average reduces 20% (55%) dead space for the floorplanning with hard (soft) macro blocks, compared with the most recent work. In particular, our floorplanner is more efficient than the previous works.