Molecular Evolution: Introns Fall into Place

AbstractThe evolutionary origin of spliceosomal introns remains elusive. The startling success of a new way of predicting intron sites suggests that the splicing machinery determines where introns are added to genes

Publishing re-usable phylogenetic trees, in theory and practice

Sharing and re-use of data are essential to the progressive and self-correcting nature of science. In recognition of this principle, journals and funding agencies have adopted policies to encourage sharing of information ('data'), including empirical data as well as computed inferences such as phylogenetic trees. 
Here we summarize an ongoing analysis of 1) current practices for sharing phylogenetic trees and associated data; 2) current barriers to effective sharing and reuse of such data; and 3) prospects for reducing these barriers to promote more widespread sharing and re-use. Currently, the technical infrastructure is available to support (with some limitations) rudimentary archiving in conjunction with manuscript publication. Yet, most published trees are not archived, and there is no community standard governing the recommended format or content to ensure a re-usable phylogenetic record. Without a shift in emphasis toward re-usability, along with technology and standards to support such a shift, the value of trees (whether disseminated via public archives, or by other means) will be limited. Interviews with actual or potential secondary consumers of phylogenetic results suggest that there is a considerable market for re-use, but that most attempts end in disappointment. Phylogenetic results available via author requests, journal web sites, archival repositories and project web sites rarely include the critical information that secondary consumers seek, such as unique identifiers for biological sources (including species sources and accession numbers), indicators of quality, and documentation of the analytical methods used to obtain the results.
Based on the analysis presented here, we suggest that enabling effective re-use entails a commitment by the research community to several changes from current practice: 1) using globally unique identifiers (GUIDs) to reference informational and material entities; 2) developing and using technology for documenting and exchanging the metadata that facilitate re-use; and 3) supporting development and use of a minimal reporting standard that indicates what data and metadata are considered essential for a re-useable phylogenetic record. We suggest that re-use may be catalyzed most rapidly by identifying and targeting (with appropriate technology) the most promising circumstances for re-use. These might include the extraction of sub-trees from large trees (for use in reconciliation, classification, and comparative analysis); the re-use of seed alignments, sub-alignments and homologized characters; the linking of phylogenies to geographic information (for use in ecology, phylogeography and biogeography); and the construction of supertrees and supermatrices

EvoIO: Community-driven standards for sustainable interoperability

Interoperability is the property that allows systems to work together independent of who created them, or how or for what purpose they were implemented. It is crucial for aggregating data from different online resources and for integrating different kinds of data. Interoperability is based on effective standards that become and remain broadly adopted. We argue that to develop and apply such standards for evolutionary and biodiversity data sustainably, we need a community-driven, open, and participatory approach. With the goal to build such an approach, the EvoIO collaboration emerged in 2009 from several NESCent-sponsored activities. EvoIO aims to be a nucleating center for developing, applying and disseminating interoperability technology that connects and coordinates between stakeholders, developers, and standards bodies.

Members of the EvoIO group have harnessed a variety of collaborative events to successfully build an initial stack of interoperability technologies that is owned by the community and open to participation. The stack addresses syntax, semantics, and programmable services, and at present includes the following components: NeXML (http://nexml.org), a NEXUS-inspired XML format that is validatable yet extensible; CDAO (http://www.evolutionaryontology.org), an ontology of comparative data analysis formalizing the semantics of evolutionary data and metadata; and PhyloWS (http://evoinfo.nescent.org/PhyloWS), a web- services interface standard for querying, retrieving, and referencing phylogenetic data on the web. Beyond demonstration prototypes, reference implementations of EvoIO stack technologies are starting to appear in production use. 

Aside from producing such information artefacts, EvoIO devotes much of its energy to applying principles of communication and organization that result in open and inclusive processes of community science. One of the key tools employed by EvoIO is the hackathon event format. Hackathons are highly collaborative, hands-on working meetings that catalyze practical innovation, train researchers, and foster cohesion as well as a sense of shared ownership in the results. In summary, we find that broad community participation, buy-in, and ownership are critical for developing interoperability in a sustainable fashion, and there are approaches and tools that can foster these effectively

Initial Implementation of a Comparative Data Analysis Ontology

Comparative analysis is used throughout biology. When entities under comparison (e.g. proteins, genomes, species) are related by descent, evolutionary theory provides a framework that, in principle, allows N-ary comparisons of entities, while controlling for non-independence due to relatedness. Powerful software tools exist for specialized applications of this approach, yet it remains under-utilized in the absence of a unifying informatics infrastructure. A key step in developing such an infrastructure is the definition of a formal ontology. The analysis of use cases and existing formalisms suggests that a significant component of evolutionary analysis involves a core problem of inferring a character history, relying on key concepts: “Operational Taxonomic Units” (OTUs), representing the entities to be compared; “character-state data” representing the observations compared among OTUs; “phylogenetic tree”, representing the historical path of evolution among the entities; and “transitions”, the inferred evolutionary changes in states of characters that account for observations. Using the Web Ontology Language (OWL), we have defined these and other fundamental concepts in a Comparative Data Analysis Ontology (CDAO). CDAO has been evaluated for its ability to represent token data sets and to support simple forms of reasoning. With further development, CDAO will provide a basis for tools (for semantic transformation, data retrieval, validation, integration, etc.) that make it easier for software developers and biomedical researchers to apply evolutionary methods of inference to diverse types of data, so as to integrate this powerful framework for reasoning into their research

Bio::NEXUS: a Perl API for the NEXUS format for comparative biological data

<p>Abstract</p> <p>Background</p> <p>Evolutionary analysis provides a formal framework for comparative analysis of genomic and other data. In evolutionary analysis, observed data are treated as the terminal states of characters that have evolved (via transitions between states) along the branches of a tree. The NEXUS standard of Maddison, et al. (1997; <it>Syst. Biol</it>. 46: 590–621) provides a portable, expressive and flexible text format for representing character-state data and trees. However, due to its complexity, NEXUS is not well supported by software and is not easily accessible to bioinformatics users and developers.</p> <p>Results</p> <p>Bio::NEXUS is an application programming interface (API) implemented in Perl, available from CPAN and SourceForge. The 22 Bio::NEXUS modules define 351 methods in 4229 lines of code, with 2706 lines of POD (Plain Old Documentation). Bio::NEXUS provides an object-oriented interface to reading, writing and manipulating the contents of NEXUS files. It closely follows the extensive explanation of the NEXUS format provided by Maddison et al., supplemented with a few extensions such as support for the NHX (New Hampshire Extended) tree format.</p> <p>Conclusion</p> <p>In spite of some limitations owing to the complexity of NEXUS files and the lack of a formal grammar, NEXUS will continue to be useful for years to come. Bio::NEXUS provides a user-friendly API for NEXUS supplemented with an extensive set of methods for manipulations such as re-rooting trees and selecting subsets of data. Bio::NEXUS can be used as glue code for connecting existing software that uses NEXUS, or as a framework for new applications.</p

Sharing and re-use of phylogenetic trees (and associated data) to facilitate synthesis

BACKGROUND Recently, various evolution-related journals adopted policies to encourage or require archiving of phylogenetic trees and associated data. Such attention to practices that promote sharing of data reflects rapidly improving information technology, and rapidly expanding potential to use this technology to aggregate and link data from previously published research. Nevertheless, little is known about current practices, or best practices, for publishing trees and associated data so as to promote re-use. FINDINGS Here we summarize results of an ongoing analysis of current practices for archiving phylogenetic trees and associated data, current practices of re-use, and current barriers to re-use. We find that the technical infrastructure is available to support rudimentary archiving, but the frequency of archiving is low. Currently, most phylogenetic knowledge is not easily re-used due to a lack of archiving, lack of awareness of best practices, and lack of community-wide standards for formatting data, naming entities, and annotating data. Most attempts at data re-use seem to end in disappointment. Nevertheless, we find many positive examples of data re-use, particularly those that involve customized species trees generated by grafting to, and pruning from, a much larger tree. CONCLUSIONS The technologies and practices that facilitate data re-use can catalyze synthetic and integrative research. However, success will require engagement from various stakeholders including individual scientists who produce or consume shareable data, publishers, policy-makers, technology developers and resource-providers. The critical challenges for facilitating re-use of phylogenetic trees and associated data, we suggest, include: a broader commitment to public archiving; more extensive use of globally meaningful identifiers; development of user-friendly technology for annotating, submitting, searching, and retrieving data and their metadata; and development of a minimum reporting standard (MIAPA) indicating which kinds of data and metadata are most important for a re-useable phylogenetic record

Mutation bias shapes the spectrum of adaptive substitutions

Evolutionary adaptation often occurs by the fixation of beneficial mutations. This mode of adaptation can be characterized quantitatively by a spectrum of adaptive substitutions, i.e., a distribution for types of changes fixed in adaptation. Recent work establishes that the changes involved in adaptation reflect common types of mutations, raising the question of how strongly the mutation spectrum shapes the spectrum of adaptive substitutions. We address this question with a codon-based model for the spectrum of adaptive amino acid substitutions, applied to three large datasets covering thousands of amino acid changes identified in natural and experimental adaptation in Saccharomyces cerevisiae, Escherichia coli, and Mycobacterium tuberculosis Using species-specific mutation spectra based on prior knowledge, we find that the mutation spectrum has a proportional influence on the spectrum of adaptive substitutions in all three species. Indeed, we find that by inferring the mutation rates that best explain the spectrum of adaptive substitutions, we can accurately recover the species-specific mutation spectra. However, we also find that the predictive power of the model differs substantially between the three species. To better understand these differences, we use population simulations to explore the factors that influence how closely the spectrum of adaptive substitutions mirrors the mutation spectrum. The results show that the influence of the mutation spectrum decreases with increasing mutational supply ([Formula: see text]) and that predictive power is strongly affected by the number and diversity of beneficial mutations

Sharing and re-use of phylogenetic trees (and associated data) to facilitate synthesis

Background Recently, various evolution-related journals adopted policies to encourage or require archiving of phylogenetic trees and associated data. Such attention to practices that promote sharing of data reflects rapidly improving information technology, and rapidly expanding potential to use this technology to aggregate and link data from previously published research. Nevertheless, little is known about current practices, or best practices, for publishing trees and associated data so as to promote re-use. Findings Here we summarize results of an ongoing analysis of current practices for archiving phylogenetic trees and associated data, current practices of re-use, and current barriers to re-use. We find that the technical infrastructure is available to support rudimentary archiving, but the frequency of archiving is low. Currently, most phylogenetic knowledge is not easily re-used due to a lack of archiving, lack of awareness of best practices, and lack of community-wide standards for formatting data, naming entities, and annotating data. Most attempts at data re-use seem to end in disappointment. Nevertheless, we find many positive examples of data re-use, particularly those that involve customized species trees generated by grafting to, and pruning from, a much larger tree. Conclusions The technologies and practices that facilitate data re-use can catalyze synthetic and integrative research. However, success will require engagement from various stakeholders including individual scientists who produce or consume shareable data, publishers, policy-makers, technology developers and resource-providers. The critical challenges for facilitating re-use of phylogenetic trees and associated data, we suggest, include: a broader commitment to public archiving; more extensive use of globally meaningful identifiers; development of user-friendly technology for annotating, submitting, searching, and retrieving data and their metadata; and development of a minimum reporting standard (MIAPA) indicating which kinds of data and metadata are most important for a re-useable phylogenetic record

NeXML: Rich, Extensible, and Verifiable Representation of Comparative Data and Metadata

In scientific research, integration and synthesis require a common understanding of where data come from, how much they can be trusted, and what they may be used for. To make such an understanding computer-accessible requires standards for exchanging richly annotated data. The challenges of conveying reusable data are particularly acute in regard to evolutionary comparative analysis, which comprises an ever-expanding list of data types, methods, research aims, and subdisciplines. To facilitate interoperability in evolutionary comparative analysis, we present NeXML, an XML standard (inspired by the current standard, NEXUS) that supports exchange of richly annotated comparative data. NeXML defines syntax for operational taxonomic units, character-state matrices, and phylogenetic trees and networks. Documents can be validated unambiguously. Importantly, any data element can be annotated, to an arbitrary degree of richness, using a system that is both flexible and rigorous. We describe how the use of NeXML by the TreeBASE and Phenoscape projects satisfies user needs that cannot be satisfied with other available file formats. By relying on XML Schema Definition, the design of NeXML facilitates the development and deployment of software for processing, transforming, and querying documents. The adoption of NeXML for practical use is facilitated by the availability of (1) an online manual with code samples and a reference to all defined elements and attributes, (2) programming toolkits in most of the languages used commonly in evolutionary informatics, and (3) input–output support in several widely used software applications. An active, open, community-based development process enables future revision and expansion of NeXML.R.A.V. received support from the CIPRES project (NSF #EF-03314953 to W.P.M.), the FP7 Marie Curie Programme (Call FP7-PEOPLE-IEF-2008—Proposal No. 237046) and, for the NeXML implementation in TreeBASE, the pPOD project (NSF IIS 0629846); P.E.M. and J.S. received support from CIPRES (NSF #EF-0331495, #EF-0715370); M.T.H. was supported by NSF (DEB-ATOL-0732920); X.X. received support from NSERC (Canada) Discovery and RTI grants; W.P.M. received support from an NSERC (Canada) Discovery grant; J.C. received support from a Google Summer of Code 2007 grant; A.P. received support from a Google Summer of Code 2010 grant

The 2006 NESCent Phyloinformatics Hackathon: A Field Report

In December, 2006, a group of 26 software developers from some of the most widely used life science programming toolkits and phylogenetic software projects converged on Durham, North Carolina, for a Phyloinformatics Hackathon, an intense five-day collaborative software coding event sponsored by the National Evolutionary Synthesis Center (NESCent). The goal was to help researchers to integrate multiple phylogenetic software tools into automated workflows. Participants addressed deficiencies in interoperability between programs by implementing “glue code” and improving support for phylogenetic data exchange standards (particularly NEXUS) across the toolkits. The work was guided by use-cases compiled in advance by both developers and users, and the code was documented as it was developed. The resulting software is freely available for both users and developers through incorporation into the distributions of several widely-used open-source toolkits. We explain the motivation for the hackathon, how it was organized, and discuss some of the outcomes and lessons learned. We conclude that hackathons are an effective mode of solving problems in software interoperability and usability, and are underutilized in scientific software development