60400
A dynamic programming approach to de novo peptide sequencing via tandem mass spectrometry
Tandem mass spectrometry fragments a large number of molecules of the same peptide sequence into charged molecules of prefix and suffix peptide subsequences and then measures mass/charge ratios of these ions. The de novo peptide sequencing problem is to reconstruct the peptide sequence from a given tandem mass spectral data of k ions. By implicitly transforming the spectral data into an NC-spectrum graph G (V, E) where /V/ = 2k + 2, we can solve this problem in O(/V//E/) time and O(/V/2) space using dynamic programming. For an ideal noise-free spectrum with only b- and y-ions, we improve the algorithm to O(/V/ + /E/) time and O(/V/) space. Our approach can be further used to discover a modified amino acid in O(/V//E/) time. The algorithms have been implemented and tested on experimental data.
10712046
Algorithms for identifying protein cross-links via tandem mass spectrometry
Cross-linking technology combined with tandem mass spectrometry (MS-MS) is a powerful method that provides a rapid solution to the discovery of protein-protein interactions and protein structures. We studied the problem of detecting cross-linked peptides and cross-linked amino acids from tandem mass spectral data. Our method consists of two steps: the first step finds two protein subsequences whose mass sum equals a given mass measured from the mass spectrometry; and the second step finds the best cross-linked amino acids in these two peptide sequences that are optimally correlated to a given tandem mass spectrum. We designed fast and space-efficient algorithms for these two steps, and implemented and tested them on experimental data of cross-linked Hemoglobin proteins.
2822926
Sorting with Fixed-length Reversals
Abstract A popular puzzle TOP-SPIN consists of a permutation of 20 numbered disks on an oval track, with a turnstile capable of reversing a string of 4 consecutive disks. The goal is to sort the disks into identity permutation using reversals. We consider the more general case of sorting n element permutations with a turnstile of size k. The problem of computing the reversal distances is of considerable importance in reconstructing the evolutionary history of the genome. The minimum reversal sequence sorting the one genome to another corresponds to the most likely evolutionary path between them. We give a complete solution for all n and k, of the number of equivalence classes of n-permutations under k-reversal, for both permutations and circular permutations. We also prove the upper and lower bounds on the reversal distances between two permutations.
31567164
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. 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, using the protein-protein interaction data from the Munich Information Center for Protein Sequences. We show that our approach outperforms other available methods for function prediction based on protein interaction data.
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.
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.
9048292
Updating mixture of principal components for error concealment
We present a new statistical modeling technique called "updating mixture of principal components" (UMPC). UMPC specifically captures the non-stationary as well as the multi-modal characteristics of the data. Real-world data such as video data typically have these two characteristics. The video content changes over time and has a multi-modal probability distribution. We apply UMPC to perform error concealment for video data transmitted over networks with losses, and show that UMPC outperforms conventional error concealment methods.
45055182
Mining frequent tree-like patterns in large datasets
Sequential pattern mining is crucial to data mining domains. This paper proposes a novel data mining approach for exploring hierarchical tree structures, named tree-like patterns, representing the relationships for a pair of items in a sequence. Using tree-like patterns, the relationships for a pair of items can be identified in terms of the cause and effect. A novel technique that efficiently counts support values for tree-like patterns using a queue structure is proposed. In addition, this paper addresses an efficient scheme for determining the frequency of a tree-like pattern in a sequence using a dynamic programming approach. Each tree-like pattern embedded in a sequence is considered to have a certain valuable meaning or the degree of importance used in different applications. Two addressed formulas are applied to determine the degree of significance for a specific sequence, which denotes the degree of consecutive items in a tree-like pattern for a sequence. The larger the degree of significance a tree-like pattern has, the more the tree-like pattern is compacted in the sequence. The characteristics differentiating the explored patterns from those obtained with other schemes are discussed. A simulation analysis of the proposed data mining approach is utilized to demonstrate its efficacy. Finally, the proposed approach is designed and implemented in a data mining system integrated into a novel e-learning platform.
17905406
On the Markovian Randomized Strategy of Controller for Markov Decision Processes
This paper focuses on the so called controller synthesis problem, which addresses the question of how to limit the internal behavior of a given system implementation to meet its specification, regardless of the behavior enforced by the environment. We consider this problem in the probabilistic setting, where the underlying model has both probabilism and nondeterminism and the nondeterministic choices in some states are assumed to be controllable while the others are under the control of an unpredictable environment. As for the specification, it is defined by probabilistic computation tree logic. We show that under the restriction that the controller exploits only Markovian randomized strategy, the existence of such a controller is decidable, which is done by a reduction to the decidability of first-order theory for reals. This also gives rise to an algorithm which can synthesize the controller if it does exist.
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.
8665982
Structure analysis for dynamic software architecture based on spatial logic
The requirement for modifying system structure during system execution is specified by dynamic software architectures. The system architecture style should remain one style or transform within a scope so that some constraints need to be imposed on during the system execution. Our work expands such an idea along two directions in the setting of formalism. The first direction is to model the system by a graph-based calculus stressing the structure. The other direction lies in that we tailor spatial logic to be a suitable logic as the system specification for structure. The model and specification are basis for the model checking algorithm that is to verify whether the system evolution satisfies some structure constraints. We invite a master-slave architecture style as a running example from the beginning and throughout the paper to demonstrate our approach. Such work can be seen as the basis of the structure analysis for architectures.