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At least 19 recordsLinked to original sources

A linear-time algorithm for computing inversion distance between signed permutations with an experimental study.

Hannenhalli and Pevzner gave the first polynomial-time algorithm for computing the inversion distance between two signed permutations, as part of the larger task of determining the shortest sequence of inversions needed to transform one permutation into the other. Their algorithm (restricted to distance calculation) proceeds in two stages: in the first stage, the overlap graph induced by the permutation is decomposed into connected components; then, in the second stage, certain graph structures (hurdles and others) are identified. Berman and Hannenhalli avoided the explicit computation of the overlap graph and gave an O(nalpha(n)) algorithm, based on a Union-Find structure, to find its connected components, where alpha is the inverse Ackerman function. Since for all practical purposes alpha(n) is a constant no larger than four, this algorithm has been the fastest practical algorithm to date. In this paper, we present a new linear-time algorithm for computing the connected components, which is more efficient than that of Berman and Hannenhalli in both theory and practice. Our algorithm uses only a stack and is very easy to implement. We give the results of computational experiments over a large range of permutation pairs produced through simulated evolution; our experiments show a speed-up by a factor of 2 to 5 in the computation of the connected components and by a factor of 1.3 to 2 in the overall distance computation.

Algorithms↗

Graph theoretical insights into evolution of multidomain proteins.

We study properties of multidomain proteins from a graph theoretical perspective. In particular, we demonstrate connections between properties of the domain overlap graph and certain variants of Dollo parsimony models. We apply our graph theoretical results to address several interrelated questions: do proteins acquire new domains infrequently, or often enough that the same combinations of domains will be created repeatedly through independent events? Once domain architectures are created do they persist? In other words, is the existence of ancestral proteins with domain compositions not observed in contemporary proteins unlikely? Our experimental results indicate that independent merges of domain pairs are not uncommon in large superfamilies.

Amino Acids↗

Food webs and the dimensionality of trophic niche space.

If the trophic niche of a kind of organism is a connected region in niche space, then it is possible for trophic niche overlaps to be described in a one-dimensional niche space if and only if the trophic niche overlap graph is an interval graph. An analysis of 30 food webs, using the combinatorial theory of interval graphs, suggests that a niche space of dimension 1 suffices, with unexpectedly high frequency and perhaps always, to describe the trophic niche overlaps implied by real food webs in single habitats. Consequently, real food webs fall in a small subset of the set of mathematically possible food webs. That real food webs are compatible with one-dimensional trophic niche spaces, more often than can be explained by chance alone, has not been noticed previously.

Journal Article↗

Common intervals and sorting by reversals: a marriage of necessity.

This paper revisits the problem of sorting by reversals with tools developed in the context of detecting common intervals. Mixing the two approaches yields new definitions and algorithms for the reversal distance computations, that apply directly on the original permutation. Traditional constructions such as recasting the signed permutation as a positive permutation, or traversing the overlap graph to analyze its connected components, are replaced by elementary definitions in terms of intervals of the permutation. This yields simple linear time algorithms that identify the essential features in a single pass over the permutation and use only simple data structures like arrays and stacks.

Algorithms↗

FAST (Flexible Analysis by Software Tool) and CHAMP (CHemico-physical AMinoacidic Parameter data bank): a new tool to investigate protein structure.

A flexible package designed to study protein structure is described. The package is devoted to the analysis of protein sequences by drawing structural profiles of specific structure-related amino acid parameters. An Aminoacidic Parameters Data Bank (CHAMP) containing 32 different series of physico-chemical parameters of amino acids is available. Sequences can be loaded from any ASCII format data bank or from keyboard. The program possesses a routine which enables easy updating of the protein data bank and CHAMP Data Bank. FAST reads statistical correlations between two plots in order to identify structural similarities. Plots can be printed, saved or used for correlation, comparison or graph overlap by using common spreadsheets (e.g. Lotus 123). Plots can be smoothed by a running mean or a running median. The program also has a special feature--a global flexibility analysis of proteins. The package runs on IBM or compatibles and requires DOS 3.0 or later.

Amino Acids↗

Two notes on genome rearrangement.

A central problem in genome rearrangement is finding a most parsimonious rearrangement scenario using certain rearrangement operations. An important problem of this type is sorting a signed genome by reversals and translocations (SBRT). Hannenhalli and Pevzner presented a duality theorem for SBRT which leads to a polynomial time algorithm for sorting a multi-chromosomal genome using a minimum number of reversals and translocations. However, there is one case for which their theorem and algorithm fail. We describe that case and suggest a correction to the theorem and the polynomial algorithm. The solution of SBRT uses a reduction to the problem of sorting a signed permutation by reversals (SBR). The best extant algorithms for SBR require quadratic time. The common approach to solve SBR is by finding a safe reversal using the overlap graph or the interleaving graph of a permutation. We describe a family of signed permutations which proves a quadratic lower bound on the number of affected vertices in the overlap/interleaving graph during any optimal sorting scenario. This implies, in particular, an Omega(n3) lower bound for Bergeron's algorithm.

Algorithms↗

Decomposition of overlapping protein complexes: a graph theoretical method for analyzing static and dynamic protein associations.

BACKGROUND: Most cellular processes are carried out by multi-protein complexes, groups of proteins that bind together to perform a specific task. Some proteins form stable complexes, while other proteins form transient associations and are part of several complexes at different stages of a cellular process. A better understanding of this higher-order organization of proteins into overlapping complexes is an important step towards unveiling functional and evolutionary mechanisms behind biological networks. RESULTS: We propose a new method for identifying and representing overlapping protein complexes (or larger units called functional groups) within a protein interaction network. We develop a graph-theoretical framework that enables automatic construction of such representation. We illustrate the effectiveness of our method by applying it to TNFalpha/NF-kappaB and pheromone signaling pathways. CONCLUSION: The proposed representation helps in understanding the transitions between functional groups and allows for tracking a protein's path through a cascade of functional groups. Therefore, depending on the nature of the network, our representation is capable of elucidating temporal relations between functional groups. Our results show that the proposed method opens a new avenue for the analysis of protein interaction networks.

Journal Article↗

[An automated and spectral differentiating dark adaptometer--initial results of a clinical study].

BACKGROUND: Routine measurement of dark adaptation is a lengthy process and the presence of a qualified operator is required. MATERIALS AND METHODS: Our dark adaptometer uses either a red or a green light-emitting diode to produce the threshold stimulus. Through an electronic circuit arrangement the dark adaptation curve is automatically measured. A computer stores the resulting data and renders the statistical analysis possible. To obtain the normal adaptation curve, 33 healthy volunteers were tested. We subsequently examined 32 patients in the clinical assay. RESULTS: The adaptation for the green test light results in an overlapping photopic/scotopic graph and is used as an analogy for the curve resulting from a white test light. The red LED produces the scotopic graph later on with a more elevated threshold. Of the patients examined, 14 with night blindness show the expected pathological results. Correlating to the type of disease, the other 18 patients without night blindness show normal dark adaptation. CONCLUSIONS: In 150 examinations the dark adaptometer proved to be easy to handle, yielding valid and reliable results. The automatic recording allows operator-independent measurements. The dark adaptation rate for red and green and the final cone and rod threshold can be evaluated. The computer control provides statistical analysis and the possibility to delegate the examination.

Adolescent↗

Haplotype-aware long-read error correction.

Error correction of long reads is an important initial step in genome assembly workflows. For organisms with ploidy greater than one, it is important to preserve haplotype-specific variation during read correction. This challenge has driven the development of several haplotype-aware correction methods. However, existing methods are based on either ad-hoc heuristics or deep learning approaches. In this paper, we introduce a rigorous formulation for this problem. Our approach builds on the minimum error correction framework used in reference-based haplotype phasing. We prove that the proposed formulation for error correction of reads in de novo context, i.e., without using a reference genome, is NP-hard. To make our exact algorithm scale to large datasets, we introduce practical heuristics. Experiments using PacBio HiFi sequencing datasets from human and plant genomes show that our approach achieves accuracy comparable to state-of-the-art methods. Implementation: https://github.com/at-cg/HALE .

Clustering↗

Effect of affinity for droplet surfaces on the fraction of analyte molecules charged during electrospray droplet fission.

The effect of uneven fissioning of mass and charge from electrospray droplets on the amount of analyte charged during the electrospray process was explored. A surface selectivity factor (S) was developed to describe the affinity of an analyte for the droplet surface, and both theoretical and experimental response curves were compared for analytes with various S values. The theoretical response curves were generated by calculating the overlap between the charge and analyte spawned from parent droplets to determine the amount of analyte charged. This overlap was then graphed as a function of analyte concentration. Differences in the amount of analyte charged during droplet fission were predicted for analytes of varying surface affinities. The issue of analyte partitioning between the surface and interior phases of the ESI droplet was also included in the discussion. This was accomplished by applying the equilibrium partitioning model to a set of offspring droplets to determine the amount of analyte on their surfaces and then calculating the overlap between fissioning analyte and excess charge. Experimental response curves resembled theoretical ones, and S values predicted from theory were in excellent agreement with those predicted on the basis of the structural characteristics of the analytes.

Chemical Phenomena↗

Uniform integration of genome mapping data using intersection graphs.

MOTIVATION: The methods for analyzing overlap data are distinct from those for analyzing probe data, making integration of the two forms awkward. Conversion of overlap data to probe-like data elements would facilitate comparison and uniform integration of overlap data and probe data using software developed for analysis of STS data. RESULTS: We show that overlap data can be effectively converted to probe-like data elements by extracting maximal sets of mutually overlapping clones. We call these sets virtual probes, since each set determines a site in the genome corresponding to the region which is common among the clones of the set. Finding the virtual probes is equivalent to finding the maximal cliques of a graph. We modify a known maximal-clique algorithm such that it finds all virtual probes in a large dataset within minutes. We illustrate the algorithm by converting fingerprint and Alu-PCR overlap data to virtual probes. The virtual probes are then analyzed using double-linkage intersection graphs and structure graphs to show that methods designed for STS data are also applicable to overlap data represented as virtual probes. Next we show that virtual probes can produce a uniform integration of different kinds of mapping data, in particular STS probe data and fingerprint and Alu-PCR overlap data. The integrated virtual probes produce longer double-linkage contigs than STS probes alone, and in conjunction with structure graphs they facilitate the identification and elimination of anomalies. Thus, the virtual-probe technique provides: (i) a new way to examine overlap data; (ii) a basis on which to compare overlap data and probe data using the same systems and standards; and (iii) a unique and useful way to uniformly integrate overlap data with probe data.

Algorithms↗

IPSEP-COLA: an incremental procedure for separation constraint layout of graphs.

We extend the popular force-directed approach to network (or graph) layout to allow separation constraints, which enforce a minimum horizontal or vertical separation between selected pairs of nodes. This simple class of linear constraints is expressive enough to satisfy a wide variety of application-specific layout requirements, including: layout of directed graphs to better show flow; layout with non-overlapping node labels; and layout of graphs with grouped nodes (called clusters). In the stress majorization force-directed layout process, separation constraints can be treated as a quadratic programming problem. We give an incremental algorithm based on gradient projection for efficiently solving this problem. The algorithm is considerably faster than using generic constraint optimization techniques and is comparable in speed to unconstrained stress majorization. We demonstrate the utility of our technique with sample data from a number of practical applications including gene-activation networks, terrorist networks and visualization of high-dimensional data.

Journal Article↗

Backward simulation of ancestors of sampled individuals.

If the population is large and the sampling mechanism is random, the coalescent is commonly used to model the haplotypes in the sample. Ordered genotypes can then be formed by random matching of the derived haplotypes. However, this approach is not realistic when (1) there is departure from random mating (e.g., dominant individuals in breeding populations or monogamy in humans), or (2) the population is small and/or the individuals in the sample are ascertained by applying some particular non-random sampling scheme, as is usually the case when considering the statistical modeling and analysis of pedigree data. For such situations, we present here a data generation method where an ancestral graph with non-overlapping generations is first generated backwards in time, using ideas from coalescent theory. Alleles are randomly assigned to the founders, and subsequently the gene flow over the entire genome is simulated forwards in time by dropping alleles down the graph according to recombination model without interference. The parameters controlling the mating behavior of generated individuals in the graph (degree of monogamy) can be tuned in order to match a particular demographic situation, without restriction to simple random mating. The performance of the approach is illustrated with a simulation example. The software (written in C-language) is freely available for research purposes at http://www.rni.helsinki.fi/~dag/.

Female↗

Interpretation of pathophysiology by laboratory data (2). Graphic display of data, dynamic pattern.

In order to display the pathophysiology of a patient more efficiently and adequately than in the static radar chart presented in the first report, a dynamic radar chart and serial line graphs using colored lines were presented. A dynamic radar chart prepared as described particularly in this report, shows the whole data of a patient along with the time course of illness by the space-saving "overlapped-drawing". Moreover serial line graphs are employed for items important for the understanding of a patient's pathophysiology or for items which show obscure change due to overlapping in the dynamic radar chart. Although this line graph is space-occupying it reveals more clearly the changes of data throughout the entire course of a patient's disease. In this second report the dynamic presentation of data and its interpretation, were presented for nine cases. This was done more efficiently and adequately than in the cases described in the first report where the display and interpretation of pathophysiology of a patient was made using merely the data of a single point.

Biometry↗

Knee radiography in the diagnosis of skeletal dysplasias.

BACKGROUND: Flattening of the epiphyses of long bones is seen in several skeletal dysplasias and standardized measurements on a radiograph of the knee to detect skeletal dysplasias using this feature have been described. Since then only two other studies in which this method was used have been published, and both included only a small number of children and neither had a control group. In addition, the Dutch National Working Group on Skeletal Dysplasias began to have doubts about the reliability of the method. We therefore decided to re-evaluate its accuracy in a population of children with and without a skeletal dysplasia. OBJECTIVE: To determine the diagnostic value of standardized measurements on conventional AP radiographs of the knee in children with a skeletal dysplasia. SUBJECTS AND METHODS: We measured the distal femoral metaphysis and epiphysis according to the published method on conventional AP radiographs of the knee in 45 healthy children and 52 children with a skeletal dysplasia. We compared graphically the height of the distal femoral epiphysis with its width and with the width of the femoral metaphysis. Receiver operating characteristic (ROC) curves were calculated for each group of children. RESULTS: All graphs showed a considerable overlap between children with a skeletal dysplasia and healthy children. The size of the area under the ROC curves for the different groups was small, varying between 0.567 and 0.653. CONCLUSIONS: This method does not discriminate between children with a skeletal dysplasia and healthy children. We therefore consider it to be of little diagnostic value.

Adolescent↗

Dynamical replica analysis of disordered Ising spin systems on finitely connected random graphs.

We study the dynamics of macroscopic observables such as the magnetization and the energy per degree of freedom in Ising spin models on random graphs of finite connectivity, with random bonds and/or heterogeneous degree distributions. To do so, we generalize existing versions of dynamical replica theory and cavity field techniques to systems with strongly disordered and locally treelike interactions. We illustrate our results via application to, e.g., +/-J spin glasses on random graphs and of the overlap in finite connectivity Sourlas codes. All results are tested against Monte Carlo simulations.

Journal Article↗

The fragment assembly string graph.

We present a concept and formalism, the string graph, which represents all that is inferable about a DNA sequence from a collection of shotgun sequencing reads collected from it. We give time and space efficient algorithms for constructing a string graph given the collection of overlaps between the reads and, in particular, present a novel linear expected time algorithm for transitive reduction in this context. The result demonstrates that the decomposition of reads into kmers employed in the de Bruijn graph approach described earlier is not essential, and exposes its close connection to the unitig approach we developed at Celera. This paper is a preliminary piece giving the basic algorithm and results that demonstrate the efficiency and scalability of the method. These ideas are being used to build a next-generation whole genome assembler called BOA (Berkeley Open Assembler) that will easily scale to mammalian genomes.

Algorithms↗

The statistical analysis of single-subject data: a comparative examination.

BACKGROUND AND PURPOSE: The purposes of this study were to examine whether the use of three different statistical methods for analyzing single-subject data led to similar results and to identify components of graphed data that influence agreement (or disagreement) among the statistical procedures. METHODS: Forty-two graphs containing single-subject data were examined. Twenty-one were AB charts of hypothetical data. The other 21 graphs appeared in Journal of Applied Behavioral Analysis, Physical Therapy, Journal of the Association for Persons With Severe Handicaps, and Journal of Behavior Therapy and Experimental Psychiatry. Three different statistical tests--the C statistic, the two-standard deviation band method, and the split-middle method of trend estimation--were used to analyze the 42 graphs. RESULTS: A relatively low degree of agreement (38%) was found among the three statistical tests. The highest rate of agreement for any two statistical procedures (71%) was found for the two-standard deviation band method and the C statistic. A logistic regression analysis revealed that overlap in single-subject graphed data was the best predictor of disagreement among the three statistical tests (beta = .49, P < .03). CONCLUSION AND DISCUSSION: The results indicate that interpretation of data from single-subject research designs is directly influenced by the method of data analysis selected. Variation exists across both visual and statistical methods of data reduction. The advantages and disadvantages of statistical and visual analysis are described.

Data Interpretation, Statistical↗