Algorithms: simultaneous error-correction and rooting for gene tree reconciliation and the gene duplication problem

<p>Abstract</p> <p>Background</p> <p>Evolutionary methods are increasingly challenged by the wealth of fast growing resources of genomic sequence information. Evolutionary events, like gene duplication, loss, and deep coalescence, account more then ever for incongruence between gene trees and the actual species tree. Gene tree reconciliation is addressing this fundamental problem by invoking the minimum number of gene duplication and losses that reconcile a rooted gene tree with a rooted species tree. However, the reconciliation process is highly sensitive to topological error or wrong rooting of the gene tree, a condition that is not met by most gene trees in practice. Thus, despite the promises of gene tree reconciliation, its applicability in practice is severely limited.</p> <p>Results</p> <p>We introduce the problem of reconciling unrooted and erroneous gene trees by simultaneously rooting and error-correcting them, and describe an efficient algorithm for this problem. Moreover, we introduce an error-corrected version of the gene duplication problem, a standard application of gene tree reconciliation. We introduce an effective heuristic for our error-corrected version of the gene duplication problem, given that the original version of this problem is NP-hard. Our experimental results suggest that our error-correcting approaches for unrooted input trees can significantly improve on the accuracy of gene tree reconciliation, and the species tree inference under the gene duplication problem. Furthermore, the efficiency of our algorithm for error-correcting reconciliation is capable of handling truly large-scale phylogenetic studies.</p> <p>Conclusions</p> <p>Our presented error-correction approach is a crucial step towards making gene tree reconciliation more robust, and thus to improve on the accuracy of applications that fundamentally rely on gene tree reconciliation, like the inference of gene-duplication supertrees.</p

Maximum likelihood models and algorithms for gene tree evolution with duplications and losses

<p>Abstract</p> <p>Background</p> <p>The abundance of new genomic data provides the opportunity to map the location of gene duplication and loss events on a species phylogeny. The first methods for mapping gene duplications and losses were based on a parsimony criterion, finding the mapping that minimizes the number of duplication and loss events. Probabilistic modeling of gene duplication and loss is relatively new and has largely focused on birth-death processes.</p> <p>Results</p> <p>We introduce a new maximum likelihood model that estimates the speciation and gene duplication and loss events in a gene tree within a species tree with branch lengths. We also provide an, in practice, efficient algorithm that computes optimal evolutionary scenarios for this model. We implemented the algorithm in the program DrML and verified its performance with empirical and simulated data.</p> <p>Conclusions</p> <p>In test data sets, DrML finds optimal gene duplication and loss scenarios within minutes, even when the gene trees contain sequences from several hundred species. In many cases, these optimal scenarios differ from the lca-mapping that results from a parsimony gene tree reconciliation. Thus, DrML provides a new, practical statistical framework on which to study gene duplication.</p

Preliminary studies of sediments from the Dobczyce drinking water reservoir

The analysis of river and lake sediments indicates that the physical, chemical, biochemical and geochemical processes that influence the fate of toxic compounds and elements in sediments are numerous and complex (for example: sorption - desorption, oxidation - reduction, ion-exchange, biological activity). Due to the above-mentioned general statement, only a long term and complex research programme can lead to satisfactory answers to the questions relating to possible changes of water and environmental quality in the future. The aim of our study consisted in physical and chemical characterisation of sediments in in-depth profiles taken from the Dobczyce reservoir in southern Poland that is a main source of drinking water for the city of Kraków. Due to morphological reasons, 7 layers of sediment samples were distinguished from the ground level to about 90 cm below (total thickness of the sediments in the sampling site). Analysis of grain size distribution and application of x-ray diffraction method, enabled mineralogical description of sediments. The use of proton-induced x-ray emission (PIXE) and atomic absorption spectrometry (AAS) revealed elemental composition of the samples (Al, P, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn). Concentrations of natural 40K and artificial 137Cs radionuclides were determined by the use of gamma spectrometry. The following facts were established: 1) the oldest (deepest) and newest, recently deposited layers of sediments are similar in their physical and chemical properties. It means that the inflow of contaminants and biogenic compounds to the reservoir has changed little since it was constructed and filled with water; 2) the severe flood in 1997 changed significantly sediment composition and, in fact, led to purification of sediments in the Dobczyce reservoir

Ultrasound evolution of parenchymal changes in the thyroid gland with autoimmune thyroiditis in children prior to the development of papillary thyroid carcinoma – a follow-up study

BackgroundFollicular cell-derived thyroid carcinoma represents the vast majority of paediatric thyroid cancers (TCs). Papillary thyroid carcinoma (PTC) accounts for over 90% of all childhood TC cases, and its incidence in paediatric patients is increasing. The objective of this follow-up study was to present the outcome of ultrasound (US) and laboratory monitoring of paediatric patients with autoimmune thyroiditis (AIT) prior to the development of PTC.Patients and methodsThis prospective study included 180 children and adolescents (132 females; 73.3%) with a suspicion of thyroid disorder referred to the Outpatient Endocrine Department. The patients were divided into four groups: 1) 28 patients with a mean age of 10.7 [standard deviation (SD), 3.1] y, in whom PTC was detected during the active surveillance of AIT [AIT(+), PTC(+) follow up (F)]; 2) 18 patients with a mean age of 12.8 (SD, 3.4) y, in whom PTC and AIT were detected upon admission (A) [AIT(+), PTC(+) A]; 3) 45 patients with a mean age of 13.0 (SD, 3.4) y, in whom PTC was detected upon admission and AIT was excluded [AIT(-), PTC(+) A]; and 4) an age- and sex-matched control group of 89 patients with AIT and with a mean age of 9.4 (SD, 3.0) y. The analysis included clinical, US, and laboratory assessment results of children on admission (groups 1–4) and during follow-up (groups 1 and 4) in the Paediatric Endocrine Outpatient Department.ResultsUpon admission of those in group 1, the US evaluation revealed a hypoechogenic thyroid gland in 12 and an irregular normoechogenic gland in 16 patients. US monitoring revealed an increase in thyroid echogenicity and an increased irregularity of the thyroid structure during the follow-up period of all of the patients from group 1. Such changes were not noticed in group 4. PTC was diagnosed at the mean time of 3.6 y (3 mo–9 y) since AIT confirmation in group 1. The mean maximum PTC diameter as per the US was significantly smaller in group 1 than in groups 2 and 3 [13.2 (10.8) mm vs. 22.2 (12.8) and 22.05 (15.4) mm]. Fewer patients in group 1 were referred to 131I than in groups 2 and 3 (71.4% vs. 94.4 and 93.3%). Interestingly, significant differences were observed in the thyroglobulin antibody (TgAb)/thyroid peroxidase antibody (TPOAb) ratio between groups 2 and 3, as opposed to group 4, at the beginning of observation [15.3 (27.6) and 3.5 (8.8] vs. 0.77 (1.9)]. In group 1, after the follow-up, an increase in the TgAb/TPOAb ratio was observed [1.2 (9.8) to 5.2 (13.5)]. There were no significant differences between groups 1–3 in labeling index Ki67, lymph nodes metastasis, extrathyroidal extension, and angioinvasion. There were no associations between thyroid-stimulating hormone, TgAb, and the extent of the disease.ConclusionThe use of thyroid US focused on the search for developing tumours in the routine follow-up of patients with AIT may not only help in the early detection of thyroid malignancies that are not clinically apparent but may also influence the invasiveness of oncological therapy and reduce the future side effects of 131I therapy. We propose that the repeat evaluation of TPOAb and TgAb warrants further exploration as a strategy to determine TC susceptibility in paediatric patients with AIT in larger multicentre studies

The great time series classification bake off: a review and experimental evaluation of recent algorithmic advances

In the last five years there have been a large number of new time series classification algorithms proposed in the literature. These algorithms have been evaluated on subsets of the 47 data sets in the University of California, Riverside time series classification archive. The archive has recently been expanded to 85 data sets, over half of which have been donated by researchers at the University of East Anglia. Aspects of previous evaluations have made comparisons between algorithms difficult. For example, several different programming languages have been used, experiments involved a single train/test split and some used normalised data whilst others did not. The relaunch of the archive provides a timely opportunity to thoroughly evaluate algorithms on a larger number of datasets. We have implemented 18 recently proposed algorithms in a common Java framework and compared them against two standard benchmark classifiers (and each other) by performing 100 resampling experiments on each of the 85 datasets. We use these results to test several hypotheses relating to whether the algorithms are significantly more accurate than the benchmarks and each other. Our results indicate that only 9 of these algorithms are significantly more accurate than both benchmarks and that one classifier, the Collective of Transformation Ensembles, is significantly more accurate than all of the others. All of our experiments and results are reproducible: we release all of our code, results and experimental details and we hope these experiments form the basis for more rigorous testing of new algorithms in the future

Reconciliation Revisited: Handling Multiple Optima when Reconciling with Duplication, Transfer, and Loss

Phylogenetic tree reconciliation is a powerful approach for inferring evolutionary events like gene duplication, horizontal gene transfer, and gene loss, which are fundamental to our understanding of molecular evolution. While duplication–loss (DL) reconciliation leads to a unique maximum-parsimony solution, duplication-transfer-loss (DTL) reconciliation yields a multitude of optimal solutions, making it difficult to infer the true evolutionary history of the gene family. This problem is further exacerbated by the fact that different event cost assignments yield different sets of optimal reconciliations. Here, we present an effective, efficient, and scalable method for dealing with these fundamental problems in DTL reconciliation. Our approach works by sampling the space of optimal reconciliations uniformly at random and aggregating the results. We show that even gene trees with only a few dozen genes often have millions of optimal reconciliations and present an algorithm to efficiently sample the space of optimal reconciliations uniformly at random in O(mn[superscript 2]) time per sample, where m and n denote the number of genes and species, respectively. We use these samples to understand how different optimal reconciliations vary in their node mappings and event assignments and to investigate the impact of varying event costs. We apply our method to a biological dataset of approximately 4700 gene trees from 100 taxa and observe that 93% of event assignments and 73% of mappings remain consistent across different multiple optima. Our analysis represents the first systematic investigation of the space of optimal DTL reconciliations and has many important implications for the study of gene family evolution.National Science Foundation (U.S.) (CAREER Award 0644282)National Institutes of Health (U.S.) (Grant RC2 HG005639)National Science Foundation (U.S.). Assembling the Tree of Life (Program) (Grant 0936234

Flare-induced fountains and buried flares in AGN

We discuss the local physical changes at the surface of an AGN accretion disk after the onset of a magnetic flare. The X-ray irradiation by a flare creates a hot spot at the disk surface where the plasma both heats up and expands in the vertical direction in order to regain the hydrostatic equilibrium. Assuming that the magnetic loop causing the flare is anchored deeply within the disk interior, we derive analytical estimates for the vertical dimension H_hot and the optical depth tau_es of the heated atmosphere as a function of the position within the spot. We perform computations for various values of the accretion rate dm/dt, the fraction f_cor of radiation dissipated within the disk corona, and the covering factor f_cover of the disk surface with flare-illuminated patches. It turns out that generally we can distinguish three characteristic radial zones within the disk showing a qualitatively different behavior of the heated material. In the innermost regions of the disk (inner zone) the expansion of the disk material is restricted by strong gravitational forces. Further out, the flare source, initially above the disk, soon becomes embedded by the expanding disk atmosphere. At these intermediate disk radii (middle zone) the material is optically thick thus greatly modifying the observed radiation by multiple Compton scattering. We show exemplary spectra models obtained from Monte Carlo simulations illustrating the trends. In the outermost regions of the disk (outer zone) the expanding material is optically thin and its influence on the observed spectra is smaller but pressure gradients in radial directions should cause the development of a fountain-like dynamical structure around the flare source. We discuss the observational consequences of our results.Comment: 12 pages, 14 figures, accepted by Astronomy & Astrophysic