716092
Complexity of Approximating Closest Substring Problems
The closest substring problem, where a short string is sought that minimizes the number of mismatches between it and each of a given set of strings, is a minimization problem with a polynomial time approximation scheme [6]. In this paper, both this problem and its maximization complement, where instead the number of matches is maximized, are examined and bounds on their hardness of approximation are proved. Related problems differing only in their objective functions, seeking either to maximize the number of strings covered by the substring or maximize the length of the substring, are also examined and bounds on their approximability proved. For this last problem of length maximization, the approximation bound of 2 is proved to be tight by presenting a 2-approximation algorithm.
19034554
SIMPROT: Using an empirically determined indel distribution in simulations of protein evolution
BackgroundGeneral protein evolution models help determine the baseline expectations for the evolution of sequences, and they have been extensively useful in sequence analysis and for the computer simulation of artificial sequence data sets.ResultsWe have developed a new method of simulating protein sequence evolution, including insertion and deletion (indel) events in addition to amino-acid substitutions. The simulation generates both the simulated sequence family and a true sequence alignment that captures the evolutionary relationships between amino acids from different sequences. Our statistical model for indel evolution is based on the empirical indel distribution determined by Qian and Goldstein. We have parameterized this distribution so that it applies to sequences diverged by varying evolutionary times and generalized it to provide flexibility in simulation conditions. Our method uses a Monte-Carlo simulation strategy, and has been implemented in a C++ program named Simprot.ConclusionSimprot will be useful for testing methods of analysis of protein sequence families particularly alignment methods, phylogenetic tree building, detection of recombination and horizontal gene transfer, and homology detection, where knowing the true course of sequence evolution is essential.
12035419
A Transition Probability Model for Amino Acid Substitutions from Blocks
Substitution matrices have been useful for sequence alignment and protein sequence comparisons. The BLOSUM series of matrices, which had been derived from a database of alignments of protein blocks, improved the accuracy of alignments previously obtained from the PAM-type matrices estimated from only closely related sequences. Although BLOSUM matrices are scoring matrices now widely used for protein sequence alignments, they do not describe an evolutionary model. BLOSUM matrices do not permit the estimation of the actual number of amino acid substitutions between sequences by correcting for multiple hits. The method presented here uses the Blocks database of protein alignments, along with the additivity of evolutionary distances, to approximate the amino acid substitution probabilities as a function of actual evolutionary distance. The PMB (Probability Matrix from Blocks) defines a new evolutionary model for protein evolution that can be used for evolutionary analyses of protein sequences. Our model is directly derived from, and thus compatible with, the BLOSUM matrices. The model has the additional advantage of being easily implemented.
1069327
DWE: Discriminating Word Enumerator
MOTIVATION
Tissue-specific transcription factor binding sites give insight into tissue-specific transcription regulation.


RESULTS
We describe a word-counting-based tool for de novo tissue-specific transcription factor binding site discovery using expression information in addition to sequence information. We incorporate tissue-specific gene expression through gene classification to positive expression and repressed expression. We present a direct statistical approach to find overrepresented transcription factor binding sites in a foreground promoter sequence set against a background promoter sequence set. Our approach naturally extends to synergistic transcription factor binding site search. We find putative transcription factor binding sites that are overrepresented in the proximal promoters of liver-specific genes relative to proximal promoters of liver-independent genes. Our results indicate that binding sites for hepatocyte nuclear factors (especially HNF-1 and HNF-4) and CCAAT/enhancer-binding protein (C/EBPbeta) are the most overrepresented in proximal promoters of liver-specific genes. Our results suggest that HNF-4 has strong synergistic relationships with HNF-1, HNF-4 and HNF-3beta and with C/EBPbeta.


AVAILABILITY
Programs are available for use over the Web at http://rulai.cshl.edu/tools/dwe.
7234685
Mining ChIP-chip data for transcription factor and cofactor binding sites
MOTIVATION
Identification of single motifs and motif pairs that can be used to predict transcription factor localization in ChIP-chip data, and gene expression in tissue-specific microarray data.


RESULTS
We describe methodology to identify de novo individual and interacting pairs of binding site motifs from ChIP-chip data, using an algorithm that integrates localization data directly into the motif discovery process. We combine matrix-enumeration based motif discovery with multivariate regression to evaluate candidate motifs and identify motif interactions. When applied to the HNF localization data in liver and pancreatic islets, our methods produce motifs that are either novel or improved known motifs. All motif pairs identified to predict localization are further evaluated according to how well they predict expression in liver and islets and according to how conserved are the relative positions of their occurrences. We find that interaction models of HNF1 and CDP motifs provide excellent prediction of both HNF1 localization and gene expression in liver. Our results demonstrate that ChIP-chip data can be used to identify interacting binding site motifs.


AVAILABILITY
Motif discovery programs and analysis tools are available on request from the authors.
1925819
Authentication of quantum messages
Authentication is a well-studied area of classical cryptography: a sender A and a receiver B sharing a classical secret key want to exchange a classical message with the guarantee that the message has not been modified or replaced by a dishonest party with control of the communication line. In this paper we study the authentication of messages composed of quantum states. We give a formal definition of authentication in the quantum setting. Assuming A and B have access to an insecure quantum channel and share a secret, classical random key, we provide a non-interactive scheme that enables A to both encrypt and authenticate an m qubit message by encoding it into m+s qubits, where the error probability decreases exponentially in the security parameter s. The scheme requires a secret key of size 2m+O(s). To achieve this, we give a highly efficient protocol for testing the purity of shared EPR pairs. It has long been known that learning information about a general quantum state will necessarily disturb it. We refine this result to show that such a disturbance can be done with few side effects, allowing it to circumvent cryptographic protections. Consequently, any scheme to authenticate quantum messages must also encrypt them. In contrast, no such constraint exists classically. This reasoning has two important consequences: It allows us to give a lower bound of 2m key bits for authenticating m qubits, which makes our protocol asymptotically optimal. Moreover, we use it to show that digitally signing quantum states is impossible.
25357010
An Analytic and Experimental Study of Multiple Channel Controllers
A multiple channel controller (MCC) is a controller which switches a given number of channels among a larger number of input/output devices and permits simultaneous access to as many devices as there are channels available. A simple queuing model for multiple channel controllers is created, and an approximate solution for this model is generated. The approximate solution is found, using simulation, to be very close for those cases examined to the actual behavior of the model. Further simulations indicate that the approximate solution of the model appears to be robust with respect to changes in some of the assumptions used in making the approximation. Trace data taken from a real system are analyzed and they confirm the predicted utility of MCC's. The problem of optimal scheduling of MCC's is briefly discussed. Alternative system configurations are compared with the objective of minimizing queuing delays.
2002086
Exploration of heterogeneous reconfigurable architectures
In contrast to early reconfigurable hardware, modern reconfigurable devices consist of a mixture of heterogeneous components. The heterogeneous components introduced in recent devices are both line and coarse-grain in their nature, and are primarily aimed at improving the speed, power consumption and area metrics of target designs. The aim of this PhD project is to look at analytical ways of exploring the design space of modern reconfigurable hardware. By automatically generating architectures and estimating benchmark performance, linear programming can eliminate architectural possibilities in an efficient way, meaning that a large number of different architectures can be examined in a fast and optimal manner.
20370847
A Set Probability Technique for Detecting Relative Time Order Across Multiple Neurons
With the development of multielectrode recording techniques, it is possible to measure the cell firing patterns of multiple neurons simultaneously, generating a large quantity of data. Identification of the firing patterns within these large groups of cells is an important and a challenging problem in data analysis. Here, we consider the problem of measuring the significance of a repeat in the cell firing sequence across arbitrary numbers of cells. In particular, we consider the question, given a ranked order of cells numbered 1 to N, what is the probability that another sequence of length n contains j consecutive increasing elements? Assuming each element of the sequence is drawn with replacement from the numbers 1 through N, we derive a recursive formula for the probability of the sequence of length j or more. For n < 2j, a closed-form solution is derived. For n 2j, we obtain upper and lower bounds for these probabilities for various combinations of parameter values. These can be computed very quickly. For a typical case with small N (<10) and large n (<3000), sequences of 7 and 8 are statistically very unlikely. A potential application of this technique is in the detection of repeats in hippocampal place cell order during sleep. Unlike most previous articles on increasing runs in random lists, we use a probability approach based on sets of overlapping sequences.
6686846
A Modified Working Set Paging Algorithm
The working set paging algorithm is known to be highly efficient, yet has the disadvantage that during changes of locality large numbers of pages are accumulated in memory Unnecessarily. The author proposes a modification of the working set algorithm called the damped working set(DWS)algorithm which resists sudden expansion of working set size and exhibits far greater stability in the number of page frames-allocated to an active process. Program address traces are analyzed to determine the effectiveness of the DWS algorithm.