ChloroMitoSSRDB 2.00: More genomes, more repeats, unifying SSRs search patterns and on-the-fly repeat detection

© The Author(s) 2015. Published by Oxford University Press. Organelle genomes evolve rapidly as compared with nuclear genomes and have been widely used for developing microsatellites or simple sequence repeats (SSRs) markers for delineating phylogenomics. In our previous reports, we have established the largest repository of organelle SSRs, ChloroMitoSSRDB, which provides access to 2161 organelle genomes (1982 mitochondrial and 179 chloroplast genomes) with a total of 5838 perfect chloroplast SSRs, 37 297 imperfect chloroplast SSRs, 5898 perfect mitochondrial SSRs and 50 355 imperfect mitochondrial SSRs across organelle genomes. In the present research, we have updated ChloroMitoSSRDB by systematically analyzing and adding additional 191 chloroplast and 2102 mitochondrial genomes. With the recent update, ChloroMitoSSRDB 2.00 provides access to a total of 4454 organelle genomes displaying a total of 40 653 IMEx Perfect SSRs (11 802 Chloroplast Perfect SSRs and 28 851 Mitochondria Perfect SSRs), 275 981 IMEx Imperfect SSRs (78 972 Chloroplast Imperfect SSRs and 197 009 Mitochondria Imperfect SSRs), 35 250 MISA (MIcroSAtellite identification tool) Perfect SSRs and 3211 MISA Compound SSRs and associated information such as location of the repeats (coding and non-coding), size of repeat, motif and length polymorphism, and primer pairs. Additionally, we have integrated and made available several in silico SSRs mining tools through a unified web-portal for in silico repeat mining for assembled organelle genomes and from next generation sequencing reads. ChloroMitoSSRDB 2.00 allows the end user to perform multiple SSRs searches and easy browsing through the SSRs using two repeat algorithms and provide primer pair information for identified SSRs for evolutionary genomics

Optimization of parameters for binary genetic algorithms.

In the GA framework, a species or population is a collection of individuals or chromosomes, usually initially generated randomly. A predefined fitness function guides selection while operators like crossover and mutation are used probabilistically in order to emulate reproduction.Genetic Algorithms (GAs) belong to the field of evolutionary computation which is inspired by biological evolution. From an engineering perspective, a GA is an heuristic tool that can approximately solve problems in which the search space is huge in the sense that an exhaustive search is not tractable. The appeal of GAs is that they can be parallelized and can give us "good" solutions to hard problems.One of the difficulties in working with GAs is choosing the parameters---the population size, the crossover and mutation probabilities, the number of generations, the selection mechanism, the fitness function---appropriate to solve a particular problem. Besides the difficulty of the application problem to be solved, an additional difficulty arises because the quality of the solution found, or the sum total of computational resources required to find it, depends on the selection of the parameters of the GA; that is, finding a correct fitness function and appropriate operators and other parameters to solve a problem with GAs is itself a difficult problem. The contributions of this dissertation, then, are: to show that there is not a linear correlation between diversity in the initial population and the performance of GAs; to show that fitness functions that use information from the problem itself are better than fitness functions that need external tuning; and to propose a relationship between selection pressure and the probabilities of crossover and mutation that improve the performance of GAs in the context of of two extreme schema: small schema, where the building block in consideration is small (each bit individually can be considered as part of the general solution), and long schema, where the building block in consideration is long (a set of interrelated bits conform part of the general solution).Theoretical and practical problems like the one-max problem and the intrusion detection problem (considered as problems with small schema) and the snake-in-the-box problem (considered as a problem with long schema) are tested under the specific hypotheses of the Dissertation.The Dissertation proposes three general hypotheses. The first one, in an attempt to measure the impact of the input over the output, study that there is not a linear correlation between diversity in the initial population and performance of GAs. The second one, proposes the use of parameters that belong to the problem itself to joint objective and constraint in fitness functions, and the third one use Holland's Schema Theorem for finding an interrelation between selection pressure and the probabilities of crossover and mutation that, if obeyed, is expected to result in better performance of the GA in terms of the solution quality found within a given number of generations and/or the number of generations to find a solution of a given quality than if the interrelation is not obeyed

Active skeleton for bacteria modeling

The investigation of spatio-temporal dynamics of bacterial cells and their molecular components requires automated image analysis tools to track cell shape properties and molecular component locations inside the cells. In the study of bacteria aging, the molecular components of interest are protein aggregates accumulated near bacteria boundaries. This particular location makes very ambiguous the correspondence between aggregates and cells, since computing accurately bacteria boundaries in phase-contrast time-lapse imaging is a challenging task. This paper proposes an active skeleton formulation for bacteria modeling which provides several advantages: an easy computation of shape properties (perimeter, length, thickness, orientation), an improved boundary accuracy in noisy images, and a natural bacteria-centered coordinate system that permits the intrinsic location of molecular components inside the cell. Starting from an initial skeleton estimate, the medial axis of the bacterium is obtained by minimizing an energy function which incorporates bacteria shape constraints. Experimental results on biological images and comparative evaluation of the performances validate the proposed approach for modeling cigar-shaped bacteria like Escherichia coli. The Image-J plugin of the proposed method can be found online at http://fluobactracker.inrialpes.fr.Comment: Published in Computer Methods in Biomechanics and Biomedical Engineering: Imaging and Visualizationto appear i

Methods for Analysing Endothelial Cell Shape and Behaviour in Relation to the Focal Nature of Atherosclerosis

The aim of this thesis is to develop automated methods for the analysis of the spatial patterns, and the functional behaviour of endothelial cells, viewed under microscopy, with applications to the understanding of atherosclerosis. Initially, a radial search approach to segmentation was attempted in order to trace the cell and nuclei boundaries using a maximum likelihood algorithm; it was found inadequate to detect the weak cell boundaries present in the available data. A parametric cell shape model was then introduced to fit an equivalent ellipse to the cell boundary by matching phase-invariant orientation fields of the image and a candidate cell shape. This approach succeeded on good quality images, but failed on images with weak cell boundaries. Finally, a support vector machines based method, relying on a rich set of visual features, and a small but high quality training dataset, was found to work well on large numbers of cells even in the presence of strong intensity variations and imaging noise. Using the segmentation results, several standard shear-stress dependent parameters of cell morphology were studied, and evidence for similar behaviour in some cell shape parameters was obtained in in-vivo cells and their nuclei. Nuclear and cell orientations around immature and mature aortas were broadly similar, suggesting that the pattern of flow direction near the wall stayed approximately constant with age. The relation was less strong for the cell and nuclear length-to-width ratios. Two novel shape analysis approaches were attempted to find other properties of cell shape which could be used to annotate or characterise patterns, since a wide variability in cell and nuclear shapes was observed which did not appear to fit the standard parameterisations. Although no firm conclusions can yet be drawn, the work lays the foundation for future studies of cell morphology. To draw inferences about patterns in the functional response of cells to flow, which may play a role in the progression of disease, single-cell analysis was performed using calcium sensitive florescence probes. Calcium transient rates were found to change with flow, but more importantly, local patterns of synchronisation in multi-cellular groups were discernable and appear to change with flow. The patterns suggest a new functional mechanism in flow-mediation of cell-cell calcium signalling

Modeling Human Atrial Patho-Electrophysiology from Ion Channels to ECG - Substrates, Pharmacology, Vulnerability, and P-Waves

Half of the patients suffering from atrial fibrillation (AF) cannot be treated adequately, today. This thesis presents multi-scale computational methods to advance our understanding of patho-mechanisms, to improve the diagnosis of patients harboring an arrhythmogenic substrate, and to tailor therapy. The modeling pipeline ranges from ion channels on the subcellular level up to the ECG on the body surface. The tailored therapeutic approaches carry the potential to reduce the burden of AF

Modeling Human Atrial Patho-Electrophysiology from Ion Channels to ECG - Substrates, Pharmacology, Vulnerability, and P-Waves

Half of the patients suffering from atrial fibrillation (AF) cannot be treated adequately, today. This book presents multi-scale computational methods to advance our understanding of patho-mechanisms, to improve the diagnosis of patients harboring an arrhythmogenic substrate, and to tailor therapy. The modeling pipeline ranges from ion channels on the subcellular level up to the ECG on the body surface. The tailored therapeutic approaches carry the potential to reduce the burden of AF