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PubMed2002

Pairwise sequence alignment using a PROSITE pattern-derived similarity score.

Existing methods for alignments are based on edition costs computed additionally position by position, according to a fixed substitution matrix: a substitution always has the same weight regardless of the position. Nevertheless the biologist favours a similarity according to his knowledge of the structure or the function of the sequences considered. In the particular case of proteins, we present a method consisting in integrating other information, such as patterns of the PROSITE databank, in the classical dynamic programming algorithm. The method consists in making an alignment by dynamic programming taking a decision not only letter by letter as in the Smith & Waterman algorithm but also by giving a reward when aligning patterns.

Algorithms↗
PubMed2004

On stochastic optimal control of partially observable nonlinear quasi Hamiltonian systems.

A stochastic optimal control strategy for partially observable nonlinear quasi Hamiltonian systems is proposed. The optimal control forces consist of two parts. The first part is determined by the conditions under which the stochastic optimal control problem of a partially observable nonlinear system is converted into that of a completely observable linear system. The second part is determined by solving the dynamical programming equation derived by applying the stochastic averaging method and stochastic dynamical programming principle to the completely observable linear control system. The response of the optimally controlled quasi Hamiltonian system is predicted by solving the averaged Fokker-Planck-Kolmogorov equation associated with the optimally controlled completely observable linear system and solving the Riccati equation for the estimated error of system states. An example is given to illustrate the procedure and effectiveness of the proposed control strategy.

Algorithms↗
PubMedDate not supplied

Flexible secondary structure based protein structure comparison applied to the detection of circular permutation.

We present a novel method for structural comparison of protein structures. The approach consists of two main phases: 1) an initial search phase where, starting from aligned pairs of secondary structure elements, the space of 3D transformations is searched for similarities and 2) a subsequent refinement phase where interim solutions are subjected to parallel, local, iterative dynamic programming in the areas of possible improvement. The proposed method combines dynamic programming for finding alignments but does not restrict solutions to be sequential. In addition, to deal with the problem of nonuniqueness of optimal similarities, we introduce a consensus scoring method in selecting the preferred similarity and provide a list of top-ranked solutions. The method, called FASE (flexible alignment of secondary structure elements), was tested on well-known data and various standard problems from the literature. The results show that FASE is able to find remote and weak similarities consistently using a reasonable run time. The method was tested (using the SCOP database) on its ability to discriminate interfold pairs from intrafold pairs at the level of the best existing methods. The method was then applied to the problem of finding circular permutations in proteins.

Animals↗
PubMed1994

A dynamic migration model with uncertainty.

The author presents "a dynamic version of the Harris-Todaro migration model where a finite population of infinitely-lived Bayesian agents choose consumption and migration decision rules as a function of their histories. The agents do not know the production functions in the two sectors and learn about them through wage draws that they receive from the stochastic production functions. The government knows the true production functions but is uninformed about the agents' beliefs, and the actual wage draws they observe. The government maximizes its welfare function using wage subsidies in the two sectors, and a migration tax. We solve the agents' dynamics programming problem, and then use the solution to solve the government's dynamic programming problem. We study the effects of government policies on the population distribution, and illustrate the model by numerically solving a particular parametric example."

Demography↗
PubMed1997

A 3D-1D substitution matrix for protein fold recognition that includes predicted secondary structure of the sequence.

In protein fold recognition, a probe amino acid sequence is compared to a library of representative folds of known structure to identify a structural homolog. In cases where the probe and its homolog have clear sequence similarity, traditional residue substitution matrices have been used to predict the structural similarity. In cases where the probe is sequentially distant from its homolog, we have developed a (7 x 3 x 2 x 7 x 3) 3D-1D substitution matrix (called H3P2), calculated from a database of 119 structural pairs. Members of each pair share a similar fold, but have sequence identity less than 30%. Each probe sequence position is defined by one of seven residue classes and three secondary structure classes. Each homologous fold position is defined by one of seven residue classes, three secondary structure classes, and two burial classes. Thus the matrix is five-dimensional and contains 7 x 3 x 2 x 7 x 3 = 882 elements or 3D-1D scores. The first step in assigning a probe sequence to its homologous fold is the prediction of the three-state (helix, strand, coil) secondary structure of the probe; here we use the profile based neural network prediction of secondary structure (PHD) program. Then a dynamic programming algorithm uses the H3P2 matrix to align the probe sequence with structures in a representative fold library. To test the effectiveness of the H3P2 matrix a challenging, fold class diverse, and cross-validated benchmark assessment is used to compare the H3P2 matrix to the GONNET, PAM250, BLOSUM62 and a secondary structure only substitution matrix. For distantly related sequences the H3P2 matrix detects more homologous structures at higher reliabilities than do these other substitution matrices, based on sensitivity versus specificity plots (or SENS-SPEC plots). The added efficacy of the H3P2 matrix arises from its information on the statistical preferences for various sequence-structure environment combinations from very distantly related proteins. It introduces the predicted secondary structure information from a sequence into fold recognition in a statistical way that normalizes the inherent correlations between residue type, secondary structure and solvent accessibility.

Algorithms↗
PubMed2006

3D volume reconstruction of a mouse brain from histological sections using warp filtering.

Sectioning tissues for optical microscopy often introduces upon the resulting sections distortions that make 3D reconstruction difficult. Here we present an automatic method for producing a smooth 3D volume from distorted 2D sections in the absence of any undistorted references. The method is based on pairwise elastic image warps between successive tissue sections, which can be computed by 2D image registration. Using a Gaussian filter, an average warp is computed for each section from the pairwise warps in a group of its neighboring sections. The average warps deform each section to match its neighboring sections, thus creating a smooth volume where corresponding features on successive sections lie close to each other. The proposed method can be used with any existing 2D image registration method for 3D reconstruction. In particular, we present a novel image warping algorithm based on dynamic programming that extends Dynamic Time Warping in 1D speech recognition to compute pairwise warps between high-resolution 2D images. The warping algorithm efficiently computes a restricted class of 2D local deformations that are characteristic between successive tissue sections. Finally, a validation framework is proposed and applied to evaluate the quality of reconstruction using both real sections and a synthetic volume.

Algorithms↗
PubMed2005

Effects of a short-term dynamic balance training program in healthy older women.

PURPOSE: Aging is associated with deterioration of the physiologic systems controlling balance. Consequently, a multitude of intervention trials has appeared in the last 2 decades attempting to improve control of balance. Effective programs often require substantial and frequent time commitments, expensive and specialized equipment, professional assistance, and clinical settings. This investigation reports the effects of a simple, short-term balance training program on dynamic balance in healthy older women. METHODS: Subjects included 11 healthy women (75.6+/-6.4 years) who participated in biweekly, 15-minute balance training sessions for 5 weeks, and 10 age-matched women (71.2+/-9.1 years) who served as controls. Balance training involved medial-lateral and anterior-posterior movements and bilateral partial squats while standing on semi-compressible foam roller-devices. Dynamic balance was quantified using functional reach in the forward, left, and right directions, and a lower extremity reach test. RESULTS: Significant increases were observed in the balance trained group: 25% in functional reach right (P=0.014) and left (P<0.001) and 16% in lower extremity reach (P=0.001). No change was noted in the control group. CONCLUSIONS: Improvements in dynamic balance can be realized following 5 weeks of dynamic balance training using this novel, simplistic, and short-term protocol.

Aged↗
PubMed1989

[Continued education from the viewpoint of the young surgeon].

Acquired operation skills suffer due to the gap filling gathering of surgical experiences in the operating room. The up to date passing on of information to surgical housemen can be improved by replacing it in part by training programs. The proposed dynamic program of an operation syllabus helps to achieve a better surgical education of housemen. Research programs should be installed as a part of surgical training. Due to the extend of their surgical duties and extra lectures housemen need a new syllabus regulation that meets the requirements stated above.

Attitude of Health Personnel↗
PubMed2006

Fast index based algorithms and software for matching position specific scoring matrices.

BACKGROUND: In biological sequence analysis, position specific scoring matrices (PSSMs) are widely used to represent sequence motifs in nucleotide as well as amino acid sequences. Searching with PSSMs in complete genomes or large sequence databases is a common, but computationally expensive task. RESULTS: We present a new non-heuristic algorithm, called ESAsearch, to efficiently find matches of PSSMs in large databases. Our approach preprocesses the search space, e.g., a complete genome or a set of protein sequences, and builds an enhanced suffix array that is stored on file. This allows the searching of a database with a PSSM in sublinear expected time. Since ESAsearch benefits from small alphabets, we present a variant operating on sequences recoded according to a reduced alphabet. We also address the problem of non-comparable PSSM-scores by developing a method which allows the efficient computation of a matrix similarity threshold for a PSSM, given an E-value or a p-value. Our method is based on dynamic programming and, in contrast to other methods, it employs lazy evaluation of the dynamic programming matrix. We evaluated algorithm ESAsearch with nucleotide PSSMs and with amino acid PSSMs. Compared to the best previous methods, ESAsearch shows speedups of a factor between 17 and 275 for nucleotide PSSMs, and speedups up to factor 1.8 for amino acid PSSMs. Comparisons with the most widely used programs even show speedups by a factor of at least 3.8. Alphabet reduction yields an additional speedup factor of 2 on amino acid sequences compared to results achieved with the 20 symbol standard alphabet. The lazy evaluation method is also much faster than previous methods, with speedups of a factor between 3 and 330. CONCLUSION: Our analysis of ESAsearch reveals sublinear runtime in the expected case, and linear runtime in the worst case for sequences not shorter than the absolute value of A(m) + m - 1, where m is the length of the PSSM and A a finite alphabet. In practice, ESAsearch shows superior performance over the most widely used programs, especially for DNA sequences. The new algorithm for accurate on-the-fly calculations of thresholds has the potential to replace formerly used approximation approaches. Beyond the algorithmic contributions, we provide a robust, well documented, and easy to use software package, implementing the ideas and algorithms presented in this manuscript.

Algorithms↗
PubMed2004

On a multimode test sequencing problem.

Test sequencing is a binary identification problem wherein one needs to develop a minimal expected cost test procedure to determine which one of a finite number of possible failure states, if any, is present. In this paper, we consider a multimode test sequencing (MMTS) problem, in which tests are distributed among multiple modes and additional transition costs will be incurred if a test sequence involves mode changes. The multimode test sequencing problem can be solved optimally via dynamic programming or AND/OR graph search methods. However, for large systems, the associated computation with dynamic programming or AND/OR graph search methods is substantial due to the rapidly increasing number of OR nodes (denoting ambiguity states and current modes) and AND nodes (denoting next modes and tests) in the search graph. In order to overcome the computational explosion, we propose to apply three heuristic algorithms based on information gain: information gain heuristic (IG), mode capability evaluation (MC), and mode capability evaluation with limited exploration of depth and degree of mode Isolation (MCLEI). We also propose to apply rollout strategies, which are guaranteed to improve the performance of heuristics, as long as the heuristics are sequentially improving. We show computational results, which suggest that the information-heuristic based rollout policies are significantly better than traditional information gain heuristic. We also show that among the three information heuristics proposed, MCLEI achieves the best tradeoff between optimality and computational complexity.

Algorithms↗
PubMed1992

A contig assembly program based on sensitive detection of fragment overlaps.

An effective computer program for assembling DNA fragments, the contig assembly program (CAP), has been developed. In the CAP program, a filter is used to eliminate quickly fragment pairs that could not possibly overlap, a dynamic programming algorithm is applied to compute the maximal-scoring overlapping alignment between each remaining pair of fragments, and a simple greedy approach is employed to assemble fragments in order of alignment scores. To identify the true fragment overlaps, the dynamic programming algorithm uses specially chosen sets of alignment parameters to tolerate sequencing errors and to penalize "mutational" changes between different copies of a repetitive sequence. The performance tests of the program on fragment data from genomic sequencing projects produced satisfactory results. The CAP program is efficient in computer time and memory; it took about 4 h to assemble a set of 1015 fragments into long contigs on a Sun workstation.

Algorithms↗
PubMed2005

A space-efficient algorithm for the constrained pairwise sequence alignment problem.

The constrained pairwise sequence alignment (CPSA) problem aims to align two given sequences by aligning their similar subsequences in the same region under the guidance of a given pattern (constraint). Let the lengths of the sequences be m, and n where n <or= m, and let r <or= n be the length of the given pattern. The optimum constrained pairwise alignment score can be computed using O(rn) space by a naive dynamic programming solution. If an optimal alignment path is desired then the space requirement of the naive dynamic programming algorithm is O(rnm). There is a divide-and-conquer algorithm that reduces the memory requirement of finding an optimal alignment for the CPSA problem to O(rn). In this paper, we present a space-efficient CPSA algorithm that returns an optimal alignment. Our analysis on real protein sequences suggests that our algorithm requires only O(n) space in practice. This algorithm is not only space efficient but also very fast. A generalization of the CPSA problem for multiple sequences is called the constrained multiple sequence alignment (CMSA) problem. Our CPSA algorithm also improves the space requirement of progressive CMSA algorithms that use solutions of CPSA problems.

Algorithms↗
PubMed2026

Exhausted CD8+ T cell fate is programmed by dynamic CTCF-mediated enhancer activation and invariant CTCF-imposed barriers.

Exhausted CD8+ T (TEX) cells undergo extensive genome reorganization during differentiation, yet the drivers of this process remain elusive. Here we show that CTCF programmed CD8+ TEX cell fates through two distinct modes of action. CTCF acquired de novo binding sites and concordantly induced open chromatin in early CD8+ TEX cells responding to chronic viral infection. The dynamic CTCF binding activated enhancers and promoted chromatin looping. Consequently, genetic ablation of CTCF diminished chromatin accessibility and interaction strength, impairing CD8+ TEX cell proliferation, effector function and bioenergetic mobilization. Conversely, invariant CTCF binding acted as essential chromatin barriers, and loss of CTCF disrupted insulation and caused aberrant chromatin self-association and undue RNA polymerase II pausing, leading to excessive activation of exhaustion- and stemness-linked genes. Thus, CTCF balanced CD8+ TEX cell differentiation by gaining dynamic binding to induce cytotoxicity and sustain metabolic fitness, while its invariant binding compartmentalized exhaustion and stemness program genes to prevent their overexuberant activation.

CCCTC-Binding Factor↗
PubMed1994

Optimizing the herd calving pattern with linear programming and dynamic probabilistic simulation.

Until recently, little attention has been paid to the influence of seasonal variation in performance and prices on the optimal calving pattern of a herd. A method was developed to determine the herd calving pattern that is farm-specific and optimal with use of linear programming. The required technical and economic parameters are calculated with a dynamic probabilistic simulation model of the dairy herd. The approach was illustrated with a situation in which the objective was to maximize the gross margin of the herd and the annual milk production of the herd was restricted, resulting in an optimal calving pattern: all heifers calved during August. When, in addition, only home-reared replacement heifers were allowed to enter the herd, heifer calvings took place from July to October. The gross margin was reduced by only Dfl. .13/100 kg of milk ($1 US = 1.80 Dfl.) as a result of the additional constraint. The sensitivity of the optimal calving pattern of herd was determined for lower reproductive performance and when seasonal price variation was ignored. The method described herein is a flexible tool for determining the optimal calving pattern of herd, taking into account farm-specific inputs and constraints.

Animal Feed↗
PubMed1993

Constrained sequence alignment.

This paper presents a dynamic programming algorithm for aligning two sequences when the alignment is constrained to lie between two arbitrary boundary lines in the dynamic programming matrix. For affine gap penalties, the algorithm requires only O(F) computations time and O(M+N) space, when F is the area of the feasible region and M and N are the sequence lengths. The result extends to concave gap penalities, with somewhat increased time and space bounds.

Algorithms↗
PubMed2006

A single network adaptive critic (SNAC) architecture for optimal control synthesis for a class of nonlinear systems.

Even though dynamic programming offers an optimal control solution in a state feedback form, the method is overwhelmed by computational and storage requirements. Approximate dynamic programming implemented with an Adaptive Critic (AC) neural network structure has evolved as a powerful alternative technique that obviates the need for excessive computations and storage requirements in solving optimal control problems. In this paper, an improvement to the AC architecture, called the "Single Network Adaptive Critic (SNAC)" is presented. This approach is applicable to a wide class of nonlinear systems where the optimal control (stationary) equation can be explicitly expressed in terms of the state and costate variables. The selection of this terminology is guided by the fact that it eliminates the use of one neural network (namely the action network) that is part of a typical dual network AC setup. As a consequence, the SNAC architecture offers three potential advantages: a simpler architecture, lesser computational load and elimination of the approximation error associated with the eliminated network. In order to demonstrate these benefits and the control synthesis technique using SNAC, two problems have been solved with the AC and SNAC approaches and their computational performances are compared. One of these problems is a real-life Micro-Electro-Mechanical-system (MEMS) problem, which demonstrates that the SNAC technique is applicable to complex engineering systems.

Animals↗
PubMed1995

A dot-matrix program with dynamic threshold control suited for genomic DNA and protein sequence analysis.

Graphical dot-matrix plots can provide the most complete and detailed comparison of two sequences. Presented here is DOTTER2, a dot-plot program for X-windows which can compare DNA or protein sequences, and also DNA versus protein. The main novel feature of DOTTER is that the user can vary the stringency cutoffs interactively, so that the dot-matrix only needs to be calculated once. This is possible thanks to a 'Greyramp tool' that was developed to change the displayed stringency of the matrix by dynamically changing the greyscale rendering of the dots. The Greyramp tool allows the user to interactively change the lower and upper score limit for the greyscale rendering. This allows exploration of the separation between signal and noise, and fine-grained visualisation of different score levels in the dot-matrix. Other useful features are dot-matrix compression, mouse-controlled zooming, sequence alignment display and saving/loading of dot-matrices. Since the matrix only has to be calculated once and since the algorithm is fast and linear in space, DOTTER is practical to use even for sequences as long as cosmids. DOTTER was integrated in the gene-modelling module of the genomic database system ACEDB3. This was done via the homology viewer BLIXEM in a way that also allows segments from the BLAST suite of searching programs to be superimposed on top of the full dot-matrix. This feature can also be used for very quick finding of the strongest matches. As examples, we analyse a Caenorhabditis elegans cosmid with several tandem repeat families, and illustrate how DOTTER can improve gene modelling.

Amino Acid Sequence↗
PubMed1996

Construction and analysis of a profile library characterizing groups of structurally known proteins.

A new sequence motif library StrProf was constructed characterizing the groups of related proteins in the PDB three-dimensional structure database. For a representative member of each protein family, which was identified by cross-referencing the PDB with the PIR superfamily classification, a group of related sequences was collected by the BLAST search against the nonredundant protein sequence database. For every group, the motifs were identified automatically according to the criteria of conservation and uniqueness of pentapeptide patterns and with a dual dynamic programming algorithm. In the StrProf library, motifs are represented by profile matrices rather than consensus patterns to allow more flexible search capabilities. Another dynamic programming algorithm was then developed to search this motif library. When the computationally derived StrProf was compared with PROSITE, which is a manually derived motif library in the best consensus pattern representation, the numbers of identified patterns were comparable. StrProf missed about one third of the PROSITE motifs, but there were also new motifs lacking in PROSITE. The new library was incorporated in SMART (Sequence Motif Analysis and Retrieval Tool), a computer tool designed to help search and annotate biologically important sites in an unknown protein sequence. The client program is available free of charge through the Internet.

Algorithms↗