Likelihood ratio intervals with Bayesian treatment of uncertainties: coverage, power and combined experiments

In this note we present studies of coverage and power for confidence intervals for a Poisson process with known background calculated using the Likelihood ratio (aka Feldman & Cousins) ordering with Bayesian treatment of uncertainties in nuisance parameters. We consider both the variant where the Bayesian integration is done in both the numerator and the denominator and the modification where the integration is done only in the numerator whereas in the denominator the likelihood is taken at the maximum likelihood estimate of the parameters. Furthermore we discuss how measurements can be combined in this framework and give an illustration with limits on the branching ratio of a rare B-meson decay recently presented by CDF/D0. A set of C++ classes has been developed which can be used to calculate confidence intervals for single or combining multiple experiments using the above algorithms and considering a variety of parameterizations to describe the uncertainties.Comment: 4 pages, 3 figures, to appear in proceedings of PhyStat2005, Oxford, UK, Sept 2005, Imperial College Pres

TMVA: The Toolkit for Multivariate Data Analysis eith ROOT

Multivariate classi cation methods based on machine learning techniques have become a fundamental ingredient to most physics analyses. The classi cation techniques themselves have also signi cantly evolved in recent years. Statisticians have found new ways to tune and to combine classi ers to further gain in performance. Integrated into the analysis framework ROOT, TMVA is a toolkit offering a large variety of multivariate classi cation algorithms. TMVA manages the simultaneous training, testing and performance evaluation of all the classi ers with a user-friendly interface, and also steers the application of the trained classi ers to data

Bandpass Filtering of DNA Elastic Modes Using Confinement and Tension

During a variety of biological and technological processes, biopolymers are simultaneously subject to both confinement and external forces. Although significant efforts have gone into understanding the physics of polymers that are only confined, or only under tension, little work has been done to explore the effects of the interplay of force and confinement. Here, we study the combined effects of stretching and confinement on a polymer’s configurational freedom. We measure the elastic response of long double-stranded DNA molecules that are partially confined to thin, nanofabricated slits. We account for the data through a model in which the DNA’s short-wavelength transverse elastic modes are cut off by applied force and the DNA’s bending stiffness, whereas long-wavelength modes are cut off by confinement. Thus, we show that confinement and stretching combine to permit tunable bandpass filtering of the elastic modes of long polymers

OrthoDB: a hierarchical catalog of animal, fungal and bacterial orthologs

The concept of orthology provides a foundation for formulating hypotheses on gene and genome evolution, and thus forms the cornerstone of comparative genomics, phylogenomics and metagenomics. We present the update of OrthoDB—the hierarchical catalog of orthologs (http://www.orthodb.org). From its conception, OrthoDB promoted delineation of orthologs at varying resolution by explicitly referring to the hierarchy of species radiations, now also adopted by other resources. The current release provides comprehensive coverage of animals and fungi representing 252 eukaryotic species, and is now extended to prokaryotes with the inclusion of 1115 bacteria. Functional annotations of orthologous groups are provided through mapping to InterPro, GO, OMIM and model organism phenotypes, with cross-references to major resources including UniProt, NCBI and FlyBase. Uniquely, OrthoDB provides computed evolutionary traits of orthologs, such as gene duplicability and loss profiles, divergence rates, sibling groups, and now extended with exon-intron architectures, syntenic orthologs and parent-child trees. The interactive web interface allows navigation along the species phylogenies, complex queries with various identifiers, annotation keywords and phrases, as well as with gene copy-number profiles and sequence homology searches. With the explosive growth of available data, OrthoDB also provides mapping of newly sequenced genomes and transcriptomes to the current orthologous group

OrthoDB: the hierarchical catalog of eukaryotic orthologs in 2011

The concept of homology drives speculation on a gene's function in any given species when its biological roles in other species are characterized. With reference to a specific species radiation homologous relations define orthologs, i.e. descendants from a single gene of the ancestor. The large-scale delineation of gene genealogies is a challenging task, and the numerous approaches to the problem reflect the importance of the concept of orthology as a cornerstone for comparative studies. Here, we present the updated OrthoDB catalog of eukaryotic orthologs delineated at each radiation of the species phylogeny in an explicitly hierarchical manner of over 100 species of vertebrates, arthropods and fungi (including the metazoa level). New database features include functional annotations, and quantification of evolutionary divergence and relations among orthologous groups. The interface features extended phyletic profile querying and enhanced text-based searches. The ever-increasing sampling of sequenced eukaryotic genomes brings a clearer account of the majority of gene genealogies that will facilitate informed hypotheses of gene function in newly sequenced genomes. Furthermore, uniform analysis across lineages as different as vertebrates, arthropods and fungi with divergence levels varying from several to hundreds of millions of years will provide essential data for uncovering and quantifying long-term trends of gene evolution. OrthoDB is freely accessible from http://cegg.unige.ch/orthod

Applying Rule Ensembles to the Search for Super-Symmetry at the Large Hadron Collider

In this note we give an example application of a recently presented predictive learning method called Rule Ensembles. The application we present is the search for super-symmetric particles at the Large Hadron Collider. In particular, we consider the problem of separating the background coming from top quark production from the signal of super-symmetric particles. The method is based on an expansion of base learners, each learner being a rule, i.e. a combination of cuts in the variable space describing signal and background. These rules are generated from an ensemble of decision trees. One of the results of the method is a set of rules (cuts) ordered according to their importance, which gives useful tools for diagnosis of the model. We also compare the method to a number of other multivariate methods, in particular Artificial Neural Networks, the likelihood method and the recently presented boosted decision tree method. We find better performance of Rule Ensembles in all cases. For example for a given significance the amount of data needed to claim SUSY discovery could be reduced by 15 % using Rule Ensembles as compared to using a likelihood method.Comment: 24 pages, 7 figures, replaced to match version accepted for publication in JHE

OrthoDB v8: update of the hierarchical catalog of orthologs and the underlying free software

Orthology, refining the concept of homology, is the cornerstone of evolutionary comparative studies. With the ever-increasing availability of genomic data, inference of orthology has become instrumental for generating hypotheses about gene functions crucial to many studies. This update of the OrthoDB hierarchical catalog of orthologs (http://www.orthodb.org) covers 3027 complete genomes, including the most comprehensive set of 87 arthropods, 61 vertebrates, 227 fungi and 2627 bacteria (sampling the most complete and representative genomes from over 11,000 available). In addition to the most extensive integration of functional annotations from UniProt, InterPro, GO, OMIM, model organism phenotypes and COG functional categories, OrthoDB uniquely provides evolutionary annotations including rates of ortholog sequence divergence, copy-number profiles, sibling groups and gene architectures. We re-designed the entirety of the OrthoDB website from the underlying technology to the user interface, enabling the user to specify species of interest and to select the relevant orthology level by the NCBI taxonomy. The text searches allow use of complex logic with various identifiers of genes, proteins, domains, ontologies or annotation keywords and phrases. Gene copy-number profiles can also be queried. This release comes with the freely available underlying ortholog clustering pipeline (http://www.orthodb.org/software

Lipid-Based Passivation in Nanofluidics

Stretching DNA in nanochannels is a useful tool for direct, visual studies of genomic DNA at the single molecule level. To facilitate the study of the interaction of linear DNA with proteins in nanochannels, we have implemented a highly effective passivation scheme based on lipid bilayers. We demonstrate virtually complete long-term passivation of nanochannel surfaces to a range of relevant reagents, including streptavidin-coated quantum dots, RecA proteins, and RecA-DNA complexes. We show that the performance of the lipid bilayer is significantly better than that of standard bovine serum albumin-based passivation. Finally, we show how the passivated devices allow us to monitor single DNA cleavage events during enzymatic degradation by DNase I. We expect that our approach will open up for detailed, systematic studies of a wide range of protein-DNA interactions with high spatial and temporal resolution