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Concept: Annotated bibliography


BACKGROUND: The availability of annotated corpora has facilitated the application of machine learning algorithms to concept extraction from clinical notes. However, high expenditure and labor are required for creating the annotations. A potential alternative is to reuse existing corpora from other institutions by pooling with local corpora, for training machine taggers. In this paper we have investigated the latter approach by pooling corpora from 2010 i2b2/VA NLP challenge and Mayo Clinic Rochester, to evaluate taggers for recognition of medical problems. The corpora were annotated for medical problems, but with different guidelines. The taggers were constructed using an existing tagging system MedTagger that consisted of dictionary lookup, part of speech (POS) tagging and machine learning for named entity prediction and concept extraction. We hope that our current work will be a useful case study for facilitating reuse of annotated corpora across institutions. RESULTS: We found that pooling was effective when the size of the local corpus was small and after some of the guideline differences were reconciled. The benefits of pooling, however, diminished as more locally annotated documents were included in the training data. We examined the annotation guidelines to identify factors that determine the effect of pooling. CONCLUSIONS: The effectiveness of pooling corpora, is dependent on several factors, which include compatibility of annotation guidelines, distribution of report types and size of local and foreign corpora. Simple methods to rectify some of the guideline differences can facilitate pooling. Our findings need to be confirmed with further studies on different corpora. To facilitate the pooling and reuse of annotated corpora, we suggest that – i) the NLP community should develop a standard annotation guideline that addresses the potential areas of guideline differences that are partly identified in this paper; ii) corpora should be annotated with a two-pass method that focuses first on concept recognition, followed by normalization to existing ontologies; and iii) metadata such as type of the report should be created during the annotation process.

Concepts: Effectiveness, Ontology, Machine learning, Learning, Annotation, Annotated bibliography, Natural language processing, Marginalia


The advent of next-generation sequencing has allowed huge amounts of DNA sequence data to be produced, advancing the capabilities of microbial ecosystem studies. The current challenge is identifying from which microorganisms and genes the DNA originated. Several tools and databases are available for annotating DNA sequences. The tools, databases and parameters used can have a significant impact on the results: naïve choice of these factors can result in a false representation of community composition and function. We use a simulated metagenome to show how different parameters affect annotation accuracy by evaluating the sequence annotation performances of MEGAN, MG-RAST, One Codex and Megablast. This simulated metagenome allowed the recovery of known organism and function abundances to be quantitatively evaluated, which is not possible for environmental metagenomes. The performance of each program and database varied, e.g. One Codex correctly annotated many sequences at the genus level, whereas MG-RAST RefSeq produced many false positive annotations. This effect decreased as the taxonomic level investigated increased. Selecting more stringent parameters decreases the annotation sensitivity, but increases precision. Ultimately, there is a trade-off between taxonomic resolution and annotation accuracy. These results should be considered when annotating metagenomes and interpreting results from previous studies.

Concepts: DNA, Bacteria, Biology, Organism, Sequence, Annotation, Annotated bibliography, Marginalia


Electron cryomicroscopy (cryo-EM) has been used to determine the atomic coordinates (models) from density maps of biological assemblies. These models can be assessed by their overall fit to the experimental data and stereochemical information. However, these models do not annotate the actual density values of the atoms nor their positional uncertainty. Here, we introduce a computational procedure to derive an atomic model from a cryo-EM map with annotated metadata. The accuracy of such a model is validated by a faithful replication of the experimental cryo-EM map computed using the coordinates and associated metadata. The functional interpretation of any structural features in the model and its utilization for future studies can be made in the context of its measure of uncertainty. We applied this protocol to the 3.3-Å map of the mature P22 bacteriophage capsid, a large and complex macromolecular assembly. With this protocol, we identify and annotate previously undescribed molecular interactions between capsid subunits that are crucial to maintain stability in the absence of cementing proteins or cross-linking, as occur in other bacteriophages.

Concepts: Microbiology, Molecule, Chemistry, Atom, Annotation, Assembly language, Annotated bibliography, Marginalia


The use of quantitative metrics to gauge the impact of scholarly publications, authors, and disciplines is predicated on the availability of reliable usage and annotation data. Citation and download counts are widely available from digital libraries. However, current annotation systems rely on proprietary labels, refer to journals but not articles or authors, and are manually curated. To address these limitations, we propose a social framework based on crowdsourced annotations of scholars, designed to keep up with the rapidly evolving disciplinary and interdisciplinary landscape. We describe a system called Scholarometer, which provides a service to scholars by computing citation-based impact measures. This creates an incentive for users to provide disciplinary annotations of authors, which in turn can be used to compute disciplinary metrics. We first present the system architecture and several heuristics to deal with noisy bibliographic and annotation data. We report on data sharing and interactive visualization services enabled by Scholarometer. Usage statistics, illustrating the data collected and shared through the framework, suggest that the proposed crowdsourcing approach can be successful. Secondly, we illustrate how the disciplinary bibliometric indicators elicited by Scholarometer allow us to implement for the first time a universal impact measure proposed in the literature. Our evaluation suggests that this metric provides an effective means for comparing scholarly impact across disciplinary boundaries.

Concepts: Scientific method, Computer, Graphic design, Annotated bibliography, Reference, Citation, Software architecture, Footnote


Currently available sequencing technologies enable quick and economical sequencing of many new eukaryotic parasite (apicomplexan or kinetoplastid) species or strains. Compared to SNP calling approaches, de novo assembly of these genomes enables researchers to additionally determine insertion, deletion and recombination events as well as to detect complex sequence diversity, such as that seen in variable multigene families. However, there currently are no automated eukaryotic annotation pipelines offering the required range of results to facilitate such analyses. A suitable pipeline needs to perform evidence-supported gene finding as well as functional annotation and pseudogene detection up to the generation of output ready to be submitted to a public database. Moreover, no current tool includes quick yet informative comparative analyses and a first pass visualization of both annotation and analysis results. To overcome those needs we have developed the Companion web server ( providing parasite genome annotation as a service using a reference-based approach. We demonstrate the use and performance of Companion by annotating two Leishmania and Plasmodium genomes as typical parasite cases and evaluate the results compared to manually annotated references.

Concepts: DNA, Gene, Genetics, Bacteria, Chromosome, Annotation, Annotated bibliography, Footnote


When using liquid chromatography/mass spectrometry (LC/MS) to perform untargeted metabolomics, it is now routine to detect tens of thousands of features from biological samples. Poor understanding of the data, however, has complicated interpretation and masked the number of unique metabolites actually being measured in an experiment. Here we place an upper bound on the number of unique metabolites detected in Escherichia coli samples analyzed with one untargeted metabolomics method. We first group multiple features arising from the same analyte, which we call “degenerate features”, using a context-driven annotation approach. Surprisingly, this analysis revealed thousands of previously unreported degeneracies that reduced the number of unique analytes to ∼2961. We then applied an orthogonal approach to remove nonbiological features from the data using the (13)C-based credentialing technology. This further reduced the number of unique analytes to less than 1000. Our 90% reduction in data is 5-fold greater than previously published studies. On the basis of the results, we propose an alternative approach to untargeted metabolomics that relies on thoroughly annotated reference data sets. To this end, we introduce the creDBle database ( ), which contains accurate mass, retention time, and MS/MS fragmentation data as well as annotations of all credentialed features.

Concepts: Mass spectrometry, Escherichia coli, Data, Data set, Annotation, Annotated bibliography, 1, Marginalia


Recent advances in sequencing technologies have resulted in an unprecedented increase in the number of metagenomes that are being sequenced world-wide. Given their volume, functional annotation of metagenomic sequence datasets requires specialized computational tools/techniques. In spite of having high accuracy, existing stand-alone functional annotation tools necessitate end-users to perform compute-intensive homology searches of metagenomic datasets against “multiple” databases prior to functional analysis. Although, web-based functional annotation servers address to some extent the problem of availability of compute resources, uploading and analyzing huge volumes of sequence data on a shared public web-service has its own set of limitations. In this study, we present COGNIZER, a comprehensive stand-alone annotation framework which enables end-users to functionally annotate sequences constituting metagenomic datasets. The COGNIZER framework provides multiple workflow options. A subset of these options employs a novel directed-search strategy which helps in reducing the overall compute requirements for end-users. The COGNIZER framework includes a cross-mapping database that enables end-users to simultaneously derive/infer KEGG, Pfam, GO, and SEED subsystem information from the COG annotations.

Concepts: Bioinformatics, Mathematics, Mathematical analysis, Sequence, Annotation, Set, Annotated bibliography, Marginalia


In 2004, the SEED ( was created to provide consistent and accurate genome annotations across thousands of genomes and as a platform for discovering and developing de novo annotations. The SEED is a constantly updated integration of genomic data with a genome database, web front end, API and server scripts. It is used by many scientists for predicting gene functions and discovering new pathways. In addition to being a powerful database for bioinformatics research, the SEED also houses subsystems (collections of functionally related protein families) and their derived FIGfams (protein families), which represent the core of the RAST annotation engine ( When a new genome is submitted to RAST, genes are called and their annotations are made by comparison to the FIGfam collection. If the genome is made public, it is then housed within the SEED and its proteins populate the FIGfam collection. This annotation cycle has proven to be a robust and scalable solution to the problem of annotating the exponentially increasing number of genomes. To date, >12 000 users worldwide have annotated >60 000 distinct genomes using RAST. Here we describe the interconnectedness of the SEED database and RAST, the RAST annotation pipeline and updates to both resources.

Concepts: DNA, Gene, Virus, Genome, Genomics, Annotation, Annotated bibliography, Marginalia


Electronic annotation of scientific data is very similar to annotation of documents. Both types of annotation amplify the original object, add related knowledge to it, and dispute or support assertions in it. In each case, annotation is a framework for discourse about the original object, and, in each case, an annotation needs to clearly identify its scope and its own terminology. However, electronic annotation of data differs from annotation of documents: the content of the annotations, including expectations and supporting evidence, is more often shared among members of networks. Any consequent actions taken by the holders of the annotated data could be shared as well. But even those current annotation systems that admit data as their subject often make it difficult or impossible to annotate at fine-enough granularity to use the results in this way for data quality control. We address these kinds of issues by offering simple extensions to an existing annotation ontology and describe how the results support an interest-based distribution of annotations. We are using the result to design and deploy a platform that supports annotation services overlaid on networks of distributed data, with particular application to data quality control. Our initial instance supports a set of natural science collection metadata services. An important application is the support for data quality control and provision of missing data. A previous proof of concept demonstrated such use based on data annotations modeled with XML-Schema.

Concepts: Quality control, Data, Annotation, Metaphysics, Annotated bibliography, Data management, Marginalia


Ontology organizes and formally conceptualizes information in a knowledge domain with a controlled vocabulary having defined terms and relationships between them. Several ontologies have been used to annotate numerous databases in biology and medicine. Due to their unambiguous nature, ontological annotations facilitate systematic description and data organization, data integration and mining, pattern recognition and statistics, as well as development of analysis and prediction tools. The Variation Ontology was developed to allow the annotation of effects, consequences and mechanisms of DNA, RNA and protein variations. Variation types are systematically organized and a detailed description of effects and mechanisms is possible. VariO is for annotating the variant, not the normal state features or properties, and requires a reference (e.g. reference sequence, reference state property, activity etc) compared to which the changes are indicated. VariO is versatile and can be used for variations ranging from genomic multiplications to single nucleotide or amino acid changes whether of genetic or non-genetic origin. VariO annotations are position specific and can be used for variations in any organism.

Concepts: DNA, Gene, Genetics, Ontology, Annotation, Annotated bibliography, Footnote, Markup language