Lucian P. Smith

Comparing likelihood and Bayesian coalescent estimation of population parameters.

We have developed a Bayesian version of our likelihood-based Markov chain Monte Carlo genealogy sampler LAMARC and compared the two versions for estimation of Θ = 4Neμ, exponential growth rate, and recombination rate. We used simulated DNA data to assess accuracy of means and support or credibility intervals. In all cases the two methods had very similar results. Some parameter combinations led to overly narrow support or credibility intervals, excluding the truth more often than the desired percentage, for both methods. However, the Bayesian approach rejected the generative parameter values significantly less often than the likelihood approach, both in cases where the level of rejection was normal and in cases where it was too high.

Antimony: a modular model definition language

MOTIVATION Model exchange in systems and synthetic biology has been standardized for computers with the Systems Biology Markup Language (SBML) and CellML, but specialized software is needed for the generation of models in these formats. Text-based model definition languages allow researchers to create models simply, and then export them to a common exchange format. Modular languages allow researchers to create and combine complex models more easily. We saw a use for a modular text-based language, together with a translation library to allow other programs to read the models as well. SUMMARY The Antimony language provides a way for a researcher to use simple text statements to create, import, and combine biological models, allowing complex models to be built from simpler models, and provides a special syntax for the creation of modular genetic networks. The libAntimony library allows other software packages to import these models and convert them either to SBML or their own internal format. AVAILABILITY The Antimony language specification and the libAntimony library are available under a BSD license from http://antimony.sourceforge.net/.

A Reappraisal of How to Build Modular, Reusable Models of Biological Systems

61Department of Bioengineering, University of Washington, Seattle, Washington, United States of America, 2Auckland Bioengineering Institute, University of Auckland,Auckland, New Zealand, 3Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America, 4Department of Molecular andIntegrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America, 5Department of Physiology and Biophysics, University of Washington,Seattle, Washington, United States of America, 6Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, Washington, UnitedStates of America

The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 1 Core.

Summary Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 1 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org/.

Simulation Experiment Description Markup Language (SED-ML) Level 1 Version 2.

The number, size and complexity of computational models of biological systems are growing at an ever increasing pace. It is imperative to build on existing studies by reusing and adapting existing models and parts thereof. The description of the structure of models is not sufficient to enable the reproduction of simulation results. One also needs to describe the procedures the models are subjected to, as recommended by the Minimum Information About a Simulation Experiment (MIASE) guidelines. This document presents Level 1 Version 2 of the Simulation Experiment Description Markup Language (SED-ML), a computer-readable format for encoding simulation and analysis experiments to apply to computational models. SED-ML files are encoded in the Extensible Markup Language (XML) and can be used in conjunction with any XML-based model encoding format, such as CellML or SBML. A SED-ML file includes details of which models to use, how to modify them prior to executing a simulation, which simulation and analysis procedures to apply, which results to extract and how to present them. Level 1 Version 2 extends the format by allowing the encoding of repeated and chained procedures.

SBML and CellML translation in Antimony and JSim

MOTIVATION The creation and exchange of biologically relevant models is of great interest to many researchers. When multiple standards are in use, models are more readily used and re-used if there exist robust translators between the various accepted formats. SUMMARY Antimony 2.4 and JSim 2.10 provide translation capabilities from their own formats to SBML and CellML. All provided unique challenges, stemming from differences in each formats inherent design, in addition to differences in functionality. AVAILABILITY AND IMPLEMENTATION Both programs are available under BSD licenses; Antimony from http://antimony.sourceforge.net/and JSim from http://physiome.org/jsim/. CONTACT lpsmith@u.washington.edu.

A Profile of Today's SBML-Compatible Software

Computational systems biologists today have a healthy selection of software resources to help them do research. Many software packages, especially those concerned with computational modeling, have adopted SBML (the Systems Biology Markup Language) as a machine-readable format to permit users to exchange models. Our group has a keen interest in understanding the landscape of SBML support. To help us ascertain the state of modern SBML-compatible software, in mid-2011 we initiated a survey of software packages that support SBML. Here we report the preliminary survey results. Based on 81 packages for which we have data so far, we summarize the trends in six areas: (1) What are the major types of functionality offered by the software systems? (2) What mathematical frameworks do they support? (3) What are their SBML-specific capabilities? (4) What other standards do they support besides SBML? (5) What are their characteristics with respect to run-time environments? And finally, (6) what are the availability and licensing terms?

SBML Level 3 package: Hierarchical Model Composition, Version 1 Release 3.

Summary Constructing a model in a hierarchical fashion is a natural approach to managing model complexity, and offers additional opportunities such as the potential to re-use model components. The SBML Level 3 Version 1 Core specification does not directly provide a mechanism for defining hierarchical models, but it does provide a mechanism for SBML packages to extend the Core specification and add additional syntactical constructs. The SBML Hierarchical Model Composition package for SBML Level 3 adds the necessary features to SBML to support hierarchical modeling. The package enables a modeler to include submodels within an enclosing SBML model, delete unneeded or redundant elements of that submodel, replace elements of that submodel with element of the containing model, and replace elements of the containing model with elements of the submodel. In addition, the package defines an optional “port” construct, allowing a model to be defined with suggested interfaces between hierarchical components; modelers can chose to use these interfaces, but they are not required to do so and can still interact directly with model elements if they so chose. Finally, the SBML Hierarchical Model Composition package is defined in such a way that a hierarchical model can be “flattened” to an equivalent, non-hierarchical version that uses only plain SBML constructs, thus enabling software tools that do not yet support hierarchy to nevertheless work with SBML hierarchical models.

Systems Biology Markup Language (SBML) Level 2 Version 5: Structures and Facilities for Model Definitions

Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 5 of SBML Level 2. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org.

The limits of fine-scale mapping

When a novel genetic trait arises in a population, it introduces a signal in the haplotype distribution of that population. Through recombination that signals history becomes differentiated from the DNA distant to it, but remains similar to the DNA close by. Fine‐scale mapping techniques rely on this differentiation to pinpoint trait loci. In this study, we analyzed the differentiation itself to better understand how much information is available to these techniques. Simulated alleles on known recombinant coalescent trees show the upper limit for fine‐scale mapping. Varying characteristics of the population being studied increase or decrease this limit. The initial uncertainty in map position has the most direct influence on the final precision of the estimate, with wider initial areas resulting in wider final estimates, though the increase is sigmoidal rather than linear. The Θ of the trait (4Nμ) is also important, with lower values for Θ resulting in greater precision of trait placement up to a point—the increase is sigmoidal as Θ decreases. Collecting data from more individuals can increase precision, though only logarithmically with the total number of individuals, so that each added individual contributes less to the final precision. However, a case/control analysis has the potential to greatly increase the effective number of individuals, as the bulk of the information lies in the differential between affected and unaffected genotypes. If haplotypes are unknown due to incomplete penetrance, much information is lost, with more information lost the less indicative phenotype is of the underlying genotype. Genet. Epidemiol. 2009.