1201195
Prediction of Protein Function Using Protein-Protein Interaction Data
Assigning functions to novel proteins is one of the most important problems in the post-genomic era. Several approaches have been applied to this problem, including analyzing gene expression patterns, phylogenetic profiles, protein fusions and protein-protein interactions. We develop a novel approach that applies the theory of Markov random fields to infer a protein's functions using protein-protein interaction data and the functional annotations of its interaction protein partners. For each function of interest and a protein, we predict the probability that the protein has that function using Bayesian approaches. Unlike in other available approaches for protein annotation where a protein has or does not have a function of interest, we give a probability for having the function. This probability indicates how confident we are about the prediction. We apply our method to predict cellular functions (43 categories including a category "others") for yeast proteins defined in the Yeast Proteome Database (YPD), using the protein-protein interaction data from the Munich Information Center for Protein Sequences (MIPS, http://mips.gsf.de). We show that our approach outperforms other available methods for function prediction based on protein interaction data.
8315237
Local Lazy Regression: Making Use of the Neighborhood to Improve QSAR Predictions
Traditional quantitative structure-activity relationship (QSAR) models aim to capture global structure-activity trends present in a data set. In many situations, there may be groups of molecules which exhibit a specific set of features which relate to their activity or inactivity. Such a group of features can be said to represent a local structure-activity relationship. Traditional QSAR models may not recognize such local relationships. In this work, we investigate the use of local lazy regression (LLR), which obtains a prediction for a query molecule using its local neighborhood, rather than considering the whole data set. This modeling approach is especially useful for very large data sets because no a priori model need be built. We applied the technique to three biological data sets. In the first case, the root-mean-square error (RMSE) for an external prediction set was 0.94 log units versus 0.92 log units for the global model. However, LLR was able to characterize a specific group of anomalous molecules with much better accuracy (0.64 log units versus 0.70 log units for the global model). For the second data set, the LLR technique resulted in a decrease in RMSE from 0.36 log units to 0.31 log units for the external prediction set. In the third case, we obtained an RMSE of 2.01 log units versus 2.16 log units for the global model. In all cases, LLR led to a few observations being poorly predicted compared to the global model. We present an analysis of why this was observed and possible improvements to the local regression approach.
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.
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.
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.
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.
16174340
A new encryption algorithm for image cryptosystems
Abstract There are two major differences of the characteristics of the text data and image data. One difference is that the size of image data is usually much larger than that of text data. The other is that plain data rarely permit loss when a compression technique is used, but image data do. In this paper, we design an efficient cryptosystem for images. Our method is based on vector quantization, which is one of the popular image compression techniques. Our method can achieve the following two goals. One goal is to design a high security image cryptosystem. The other goal is to reduce computational complexity of the encryption and decryption algorithms.
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.
16035611
Swimming across the Pacific: a VR swimming interface
A locomotion interface for swimming and floating in a virtual ocean is part of the interactive installation of the Swimming Across the Pacific artwork. In the 'Swimming Across the Pacific' artwork, the authors create a space for collaborative artwork in an airplane by having a swimmer swim while flying across the Pacific Ocean. The swimmer's swimming represents a transformation of the airplane into an art gallery where the medium is the airplane, much as Misheff transformed the Queen Elizabeth II while he swam during her journey. By using elements such as the AV system, food, and clothing in the airplane for expression, fellow artists, scientists, engineers, musicians, media, and other passengers participate together to create artwork. This article is available with a short video documentary on CD-ROM.
26835658
On the test allocations for the best lower bound performance of partition testing
A partition testing strategy divides the program's input domain into subdomains according to a partitioning scheme, and selects test cases from each subdomain according to a test allocation scheme. Previous studies have shown that partition testing strategies can be very effective or very ineffective in detecting faults, depending on both the partitioning scheme and the test allocation scheme. Given a partitioning scheme, the maximin criterion chooses a test allocation scheme that will maximally improve the lower bound performance of the partition testing strategy. In an earlier work, we have proved that the Basic Maximin Algorithm can generate such a test allocation scheme. In this paper, we derive further properties of the Basic Maximin Algorithm and present the Complete Maximin Algorithm that generates all possible test allocation schemes that satisfy the maximin criterion.
43120543
A simulation study on some heuristics for test suite reduction
In order to test a program, software testers must first define a testing objective. From this a test suite is then constructed. In fact, some subsets of the constructed test suite may still satisfy the same testing objective. Such subsets are referred to as representative sets of the test suite. Finding the optimal representative sets of the test suite reduction problem is known to be NP-complete. Different heuristics, including G, GE, grE and H, have been proposed by different researchers. However, it has been demonstrated that none of these four heuristics are guaranteed to deliver smaller sized representative sets. This paper presents the result of a simulation study of these four heuristics. The aim of the study is to provide application guidelines for choosing the most appropriate heuristic for test suite reduction.