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Mapping gene interactions within tissues/cell types plays a crucial role in understanding the genetic basis of human physiology and disease. Tissue functional gene networks (FGNs) are essential models for mapping complex gene interactions. We present TissueNexus, a database of 49 human tissue/cell line FGNs constructed by integrating heterogeneous genomic data. We adopted an advanced machine learning approach for data integration because Bayesian classifiers, which is the main approach used for constructing existing tissue gene networks, cannot capture the interaction and nonlinearity of genomic features well. A total of 1,341 RNA-seq datasets containing 52,087 samples were integrated for all of these networks. Because the tissue label for RNA-seq data may be annotated with different names or be missing, we performed intensive hand-curation to improve quality. We further developed a user-friendly database for network search, visualization, and functional analysis. We illustrate the application of TissueNexus in prioritizing disease genes. The database is publicly available at https://www.diseaselinks.com/TissueNexus/.

Background Hypersensitivity pneumonitis (HP) is caused by a variety of antigens and low-molecular-weight chemicals, often through occupational exposure. Making a diagnosis of HP and identifying a cause are challenging. Cryptogenic cases are frequently reported, and missing or incomplete exposure histories can cause misclassification. Aims To provide an evidence-based compendium of sources of exposure and causes of HP for the clinician, through systematic review of medical literature. Methods Articles related to HP causative agents and occupational exposure were searched from the databases OVID Medline (1946 to October 2020) and EMBASE (1974 to October 2020). Abstracts and full texts of articles were screened by two reviewers. Data on causative antigens, occupational source of exposure and any associated eponymous name were extracted and grouped according to source of exposure. Results A total of 1790 articles were identified, from which 305 articles met the inclusion criteria. An additional 22 articles were identified from citation lists of the selected review articles. Sources of exposure identified for HP were sorted into 14 categories of work (agricultural, plant matter processing, wood, animal-related, foodstuff, food processing, metal processing, polymers, other manufacturing, chemicals, aerosolized water, service, waste and sewage and wind instruments). Conclusions This work is a comprehensive list of occupational causative agents and exposures causing HP. Cases are grouped by source of exposure, allowing an immediately accessible compendium of causes for use during occupational exposure assessment, which could also form the basis for a clinical questionnaire.

As part of the cultural revival that accompanied the Zionist revolution, important literary projects were created, providing ideological support for the Zionist project, enriching the newly revived Hebrew culture and redefining the Jewish bookshelf. Within this diverse cultural work, the project of the anthologies was formed. These projects were led at the beginning by disciples of Ahad Ha'am—the founder of the cultural stream in Zionism. Religious Zionism, which during the British Mandate in Palestine had struggled for its place among the pioneers, also sought to initiate its own literary projects. However, its scholars came to compile anthologies individually rather than through the Movement. Their interest was sparked by a combination of modern Jewish scientific research, an aspiration to enrich Jewish literature, and the theoretical and practical challenge presented by national revival. The two most prominent efforts of this sort during the Mandate period: Otzar HaGeonim (by Benjamin Menashe Levin), and Seder Kiddushin ve-Nissu'in Aharei Hatimat ha-Talmud (by Abraham Chaim Freimann), reflected two different trends in religious Zionism. The first, expanding the study of Torah, touched on the theoretical side of the Talmud in Jewish literature and enjoyed Orthodox consensus. The second, concerned with the renewal of halacha, touched on the practical side of religious law throughout the ages and sought to locate, collect, and analyze judgments and rabbinic rulings from Jewish consortiums in the post-Talmudic period, in order to formulate legal precedents that could resolve halachic problems that might arise in the future in Eretz Israel, where the Jewish People were about to establish an independent national state.

Viruses are responsible for causing various epidemics and pandemics with a high mortality rate e.g. ongoing SARS-CoronaVirus-2 crisis. The discovery of novel antivirals remains a challenge but drug repurposing is emerging as a potential solution to develop antivirals in a cost-effective manner. In this regard, we collated the information of repurposed drugs tested for antiviral activity from literature and presented it in the form of a user-friendly web server named ‘DrugRepV’. The database contains 8485 entries (3448 unique) with biological, chemical, clinical and structural information of 23 viruses responsible to cause epidemics/pandemics. The database harbors browse and search options to explore the repurposed drug entries. The data can be explored by some important fields like drugs, viruses, drug targets, clinical trials, assays, etc. For summarizing the data, we provide overall statistics of the repurposed candidates. To make the database more informative, it is hyperlinked to various external repositories like DrugBank, PubChem, NCBI-Taxonomy, Clinicaltrials.gov, World Health Organization and many more. ‘DrugRepV’ database (https://bioinfo.imtech.res.in/manojk/drugrepv/) would be highly useful to the research community working to develop antivirals.

Kinases form the backbone of numerous cell signaling pathways, with their dysfunction similarly implicated in multiple pathologies. Further facilitated by their druggability, kinases are a major focus of therapeutic development efforts in diseases such as cancer, infectious disease and autoimmune disorders. While their importance is clear, the role or biological function of nearly one-third of kinases is largely unknown. Here, we describe a data resource, the Dark Kinase Knowledgebase (DKK; https://darkkinome.org), that is specifically focused on providing data and reagents for these understudied kinases to the broader research community. Supported through NIH’s Illuminating the Druggable Genome (IDG) Program, the DKK is focused on data and knowledge generation for 162 poorly studied or ‘dark’ kinases. Types of data provided through the DKK include parallel reaction monitoring (PRM) peptides for quantitative proteomics, protein interactions, NanoBRET reagents, and kinase-specific compounds. Higher-level data is similarly being generated and consolidated such as tissue gene expression profiles and, longer-term, functional relationships derived through perturbation studies. Associated web tools that help investigators interrogate both internal and external data are also provided through the site. As an evolving resource, the DKK seeks to continually support and enhance knowledge on these potentially high-impact druggable targets.

Phylogenomic and paleontological data constitute complementary resources for unraveling the phylogenetic relationships and divergence times of lineages, yet few studies have attempted to fully integrate them. Several unique properties of echinoids (sea urchins) make them especially useful for such synthesizing approaches, including a remarkable fossil record that can be incorporated into explicit phylogenetic hypotheses. We revisit the phylogeny of crown group Echinoidea using a total-evidence dating approach that combines the largest phylogenomic data set for the clade, a large-scale morphological matrix with a dense fossil sampling, and a novel compendium of tip and node age constraints. To this end, we develop a novel method for subsampling phylogenomic data sets that selects loci with high phylogenetic signal, low systematic biases, and enhanced clock-like behavior. Our results demonstrate that combining different data sources increases topological accuracy and helps resolve conflicts between molecular and morphological data. Notably, we present a new hypothesis for the origin of sand dollars, and restructure the relationships between stem and crown echinoids in a way that implies a long stretch of undiscovered evolutionary history of the crown group in the late Paleozoic. Our efforts help bridge the gap between phylogenomics and phylogenetic paleontology, providing a model example of the benefits of combining the two. [Echinoidea; fossils; paleontology; phylogenomics; time calibration; total evidence.]

Motivation Although gene set enrichment analysis has become an integral part of high-throughput gene expression data analysis, the assessment of enrichment methods remains rudimentary and ad hoc. In the absence of suitable gold standards, evaluations are commonly restricted to selected datasets and biological reasoning on the relevance of resulting enriched gene sets. Results We develop an extensible framework for reproducible benchmarking of enrichment methods based on defined criteria for applicability, gene set prioritization and detection of relevant processes. This framework incorporates a curated compendium of 75 expression datasets investigating 42 human diseases. The compendium features microarray and RNA-seq measurements, and each dataset is associated with a precompiled GO/KEGG relevance ranking for the corresponding disease under investigation. We perform a comprehensive assessment of 10 major enrichment methods, identifying significant differences in runtime and applicability to RNA-seq data, fraction of enriched gene sets depending on the null hypothesis tested and recovery of the predefined relevance rankings. We make practical recommendations on how methods originally developed for microarray data can efficiently be applied to RNA-seq data, how to interpret results depending on the type of gene set test conducted and which methods are best suited to effectively prioritize gene sets with high phenotype relevance. Availability http://bioconductor.org/packages/GSEABenchmarkeR Contact ludwig.geistlinger@sph.cuny.edu

Motivation The availability of thousands of genome-wide coupling chromatin immunoprecipitation (ChIP)-Seq datasets across hundreds of transcription factors (TFs) and cell lines provides an unprecedented opportunity to jointly analyze large-scale TF-binding in vivo, making possible the discovery of the potential interaction and cooperation among different TFs. The interacted and cooperated TFs can potentially form a transcriptional regulatory module (TRM) (e.g. co-binding TFs), which helps decipher the combinatorial regulatory mechanisms. Results We develop a computational method tfLDA to apply state-of-the-art topic models to multiple ChIP-Seq datasets to decipher the combinatorial binding events of multiple TFs. tfLDA is able to learn high-order combinatorial binding patterns of TFs from multiple ChIP-Seq profiles, interpret and visualize the combinatorial patterns. We apply the tfLDA to two cell lines with a rich collection of TFs and identify combinatorial binding patterns that show well-known TRMs and related TF co-binding events. Availability and implementation A software R package tfLDA is freely available at https://github.com/lichen-lab/tfLDA. Supplementary information Supplementary data are available at Bioinformatics online.

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose This report describes the development and maintenance of a table to present an assessment of evidence for treatments used in patients with coronavirus disease 2019 (COVID-19). Summary AHFS Drug Information (AHFS DI) (American Society of Health-System Pharmacists, Bethesda, MD) is ASHP’s evidence-based drug compendium that contains drug monographs written for pharmacists and other healthcare professionals. The professional editorial and analytical staff of pharmacists critically evaluate published evidence to develop drug monographs for AHFS DI. In response to the global COVID-19 pandemic, these skills were applied to assess emerging evidence for COVID-19–related treatments, and the information was compiled into a new resource for pharmacists and other healthcare professionals to use at the point of care. A list of therapies was developed and prioritized based on review of scientific and public discussions on the use of these therapies in patients with COVID-19; certain therapies used for supportive care and therapies that might theoretically be harmful to patients with COVID-19 also were considered for inclusion. Potential treatments were identified, and the evidence for use in patients with COVID-19 was assessed and summarized in a table format. Information presented for each therapy included the rationale for use, summaries of clinical trials or experience, trial registry numbers, and dosage regimens. Comments on safety and efficacy, including limitations of available data, were presented along with recommendations from recognized authorities. The editorial team continued to add new therapies to the table and update existing entries as new evidence emerged. Conclusion A comprehensive table that summarized available evidence for potential treatments for patients with COVID-19 was developed. The table format enabled the drug information editorial staff to provide ongoing updates as new information emerged during the pandemic.

OrthoList, a compendium of Caenorhabditis elegans genes with human orthologs compiled in 2011 by a meta-analysis of four orthology-prediction methods, has been a popular tool for identifying conserved genes for research into biological and disease mechanisms. However, the efficacy of orthology prediction depends on the accuracy of gene-model predictions, an ongoing process, and orthology-prediction algorithms have also been updated over time. Here we present OrthoList 2 (OL2), a new comparative genomic analysis between C. elegans and humans, and the first assessment of how changes over time affect the landscape of predicted orthologs between two species. Although we find that updates to the orthology-prediction methods significantly changed the landscape of C. elegans–human orthologs predicted by individual programs and—unexpectedly—reduced agreement among them, we also show that our meta-analysis approach “buffered” against changes in gene content. We show that adding results from more programs did not lead to many additions to the list and discuss reasons to avoid assigning “scores” based on support by individual orthology-prediction programs; the treatment of “legacy” genes no longer predicted by these programs; and the practical difficulties of updating due to encountering deprecated, changed, or retired gene identifiers. In addition, we consider what other criteria may support claims of orthology and alternative approaches to find potential orthologs that elude identification by these programs. Finally, we created a new web-based tool that allows for rapid searches of OL2 by gene identifiers, protein domains [InterPro and SMART (Simple Modular Architecture Research Tool], or human disease associations ([OMIM (Online Mendelian Inheritence in Man], and also includes available RNA-interference resources to facilitate potential translational cross-species studies.

This essay focuses on Garnet Wolseley’s controversial war instruction manual, The Soldier’s Pocket-book for Field Service (1869). While the Pocket-book’s contribution to discussions of reading and soldiers’ education has carved out a significant place for it in Victorian military history, in its day it was constantly contested and undermined by contradictory representations, as a book much talked about but little read. This essay is an exercise in tracing these eccentric reception histories, as an acute reminder that books may well have vibrant intellectual lives without actually being read. To examine the literary and material circulation of the Pocket-book in the late nineteenth century, it draws on archival research in the Macmillan Archive and Wolseley’s private papers to discuss the genesis of the text not just as a compendium of information but also as an object that is handled, carried, and exchanged. I juxtapose these considerations with episodes in the representation of the Pocket-book: i...

Authentication of medicinal materials by deoxyribonucleic acid (DNA) technology is gaining popularity. In 2010, our team has created Medicinal Materials DNA Barcode Database (MMDBD) version 1.0 to provide an interactive database for documenting DNA barcode sequences of medicinal materials. This database now contains DNA barcode sequences of medicinal materials listed in the Chinese Pharmacopoeia, Dietary Supplements Compendium and Herbal Medicine Compendium of the US Pharmacopoeia and selected adulterants. The data archive is regularly updated and currently it stores 62 011 DNA sequences of 2111 medicinal materials. Our team has recently completed the major improvement on the interfaces and incorporated essential bioinformatics tools to facilitate the authentication work. MMDBD version 1.5 contains detailed information of each medicinal material including their material names, medical part, pharmacopeia information, biological classification in rank of family and status on the Convention on International Trade in Endangered Species of Wild Fauna and Flora and the International Union for Conservation of Nature’s Red List of Threatened Species, if any. DNA sequences can be retrieved by search in Latin scientific name, Chinese name, family name, material name, medical part and simplified Chinese character stroke. A `BLAST’-based engine for searching DNA sequences is included in the MMDBD version 1.5. Since primer design is a key step in DNA barcoding authentication, we have integrated the `Clustal Omega alignment tool’ and `Primer3’ in the form of web interface. These new tools facilitate multiple sequence comparison and the design of primers for amplification of a target DNA barcode region, allowing DNA barcoding authentication.

In view of the widely varying energy spectra encountered in practical situations, accuracy of neutron dose assessment requires detailed knowledge of detector responses and workplace conditions to achieve an adequate level of protection. If the neutron spectrum should be a priori unknown and no measurement of the workplace spectrum is available, the 'Compendium of Neutron Spectra and Detector Responses for Radiation Protection Purposes' published in the International Atomic Energy Agency Technical Report Series offers a broad range of reference spectra that may be appropriate for many applications. The proposed approach applies a correction factor based on the ratio of 'personal dose equivalent indices' for a particular workplace spectrum and a reference field used for calibration of the dosemeter response. Amendments in the definition of operational quantities as well as introduction of new modalities that, for example, may be expected to give increased importance to high-energy neutrons necessitate frequent revision of the Compendium. Results from the European Radiation Dosimetry Group Intercomparison 2012 for neutron personal dosemeters provide evidence that workplace fields are insufficiently reflected. This is proposed to be considered as an improvement opportunity.

A few years ago, I agreed to write an entry for the International Studies Association (ISA) Compendium entitled “Alliances and Arms: The Quest for Security” (Denemark 2010). The submission was requested by the Scientific Study of International Processes (SSIP) Section editors, Paul Diehl and Jim Morrow. My colleague Cliff Morgan and I were tasked with reviewing the literature on alliances and arms, with a focus on the contributions of SSIP style work. When the volume containing our contribution arrived in the mail sometime later, I discovered that the very next entry alphabetically in the compendium was entitled “Alliances and War,” and was written by Patricia Weitsman, commissioned by the International Security Studies Section (ISSS). Until the volume came out, Cliff and I were unaware that Patty was working on a similar entry, and I expect she was not aware of our contribution either. After reading the two entries, I was struck by the separation of communities concerned with similar problems. Weitsman’s compendium entry cites 156 studies. Leeds and Morgan’s cites ninety-six studies. The two share twenty-nine citations in common—19 percent of the Weitsman citations and 30 percent of the Leeds and Morgan citations. The topics of the two essays are not identical, and we were specifically told to focus on literature related to the traditions of our sections, which surely helps explain some of the differences. Still, it seems that the two essays attempt to answer similar questions relying on different bodies of work. But do they reach the same conclusions? The answer is yes and no. In explaining alliance formation, both essays begin from the same starting point—balance of power theories. The first major difference between the two essays is that Weitsman concludes that “balancing is a central role that alliances …

Motivation: Leveraging the large compendium of genomic data to predict biomedical pathways and specific mechanisms of protein interactions genome-wide in metazoan organisms has been challenging. In contrast to unicellular organisms, biological and technical variation originating from diverse tissues and cell-lineages is often the largest source of variation in metazoan data compendia. Therefore, a new computational strategy accounting for the tissue heterogeneity in the functional genomic data is needed to accurately translate the vast amount of human genomic data into specific interaction-level hypotheses. Results: We developed an integrated, scalable strategy for inferring multiple human gene interaction types that takes advantage of data from diverse tissue and cell-lineage origins. Our approach specifically predicts both the presence of a functional association and also the most likely interaction type among human genes or its protein products on a whole-genome scale. We demonstrate that directly incorporating tissue contextual information improves the accuracy of our predictions, and further, that such genome-wide results can be used to significantly refine regulatory interactions from primary experimental datasets (e.g. ChIP-Seq, mass spectrometry). Availability and implementation: An interactive website hosting all of our interaction predictions is publically available at http://pathwaynet.princeton.edu. Software was implemented using the open-source Sleipnir library, which is available for download at https://bitbucket.org/libsleipnir/libsleipnir.bitbucket.org. Contact: ogt@cs.princeton.edu Supplementary information: Supplementary data are available at Bioinformatics online.

The International Union of Basic and Clinical Pharmacology/British Pharmacological Society (IUPHAR/BPS) Guide to PHARMACOLOGY (http://www.guidetopharmacology.org) is a new open access resource providing pharmacological, chemical, genetic, functional and pathophysiological data on the targets of approved and experimental drugs. Created under the auspices of the IUPHAR and the BPS, the portal provides concise, peer-reviewed overviews of the key properties of a wide range of established and potential drug targets, with in-depth information for a subset of important targets. The resource is the result of curation and integration of data from the IUPHAR Database (IUPHAR-DB) and the published BPS 'Guide to Receptors and Channels' (GRAC) compendium. The data are derived from a global network of expert contributors, and the information is extensively linked to relevant databases, including ChEMBL, DrugBank, Ensembl, PubChem, UniProt and PubMed. Each of the approximately 6000 small molecule and peptide ligands is annotated with manually curated 2D chemical structures or amino acid sequences, nomenclature and database links. Future expansion of the resource will complete the coverage of all the targets of currently approved drugs and future candidate targets, alongside educational resources to guide scientists and students in pharmacological principles and techniques

Motivation: Non-coding RNA (ncRNA) genes are increasingly acknowledged for their importance in the human genome. However, there is no comprehensive non-redundant database for all such human genes. Results: We leveraged the effective platform of GeneCards, the human gene compendium, together with the power of fRNAdb and additional primary sources, to judiciously unify all ncRNA gene entries obtainable from 15 different primary sources. Overlapping entries were clustered to unified locations based on an algorithm employing genomic coordinates. This allowed GeneCards’ gamut of relevant entries to rise ∼5-fold, resulting in ∼80 000 human non-redundant ncRNAs, belonging to 14 classes. Such ‘grand unification’ within a regularly updated data structure will assist future ncRNA research. Availability and implementation: All of these non-coding RNAs are included among the ∼122 500 entries in GeneCards V3.09, along with pertinent annotation, automatically mined by its built-in pipeline from 100 data sources. This information is available at www.genecards.org. Contact: Frida.Belinky@weizmann.ac.il Supplementary information: Supplementary data are available at Bioinformatics online.

IMP (Integrative Multi-species Prediction), originally released in 2012, is an interactive web server that enables molecular biologists to interpret experimental results and to generate hypotheses in the context of a large cross-organism compendium of functional predictions and networks. The system provides biologists with a framework to analyze their candidate gene sets in the context of functional networks, expanding or refining their sets using functional relationships predicted from integrated high-throughput data. IMP 2.0 integrates updated prior knowledge and data collections from the last three years in the seven supported organisms (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Danio rerio, Caenorhabditis elegans, and Saccharomyces cerevisiae) and extends function prediction coverage to include human disease. IMP identifies homologs with conserved functional roles for disease knowledge transfer, allowing biologists to analyze disease contexts and predictions across all organisms. Additionally, IMP 2.0 implements a new flexible platform for experts to generate custom hypotheses about biological processes or diseases, making sophisticated data-driven methods easily accessible to researchers. IMP does not require any registration or installation and is freely available for use at http://imp.princeton.edu.

Motivation: Query-based biclustering techniques allow interrogating a gene expression compendium with a given gene or gene list. They do so by searching for genes in the compendium that have a profile close to the average expression profile of the genes in this query-list. As it can often not be guaranteed that the genes in a long query-list will all be mutually coexpressed, it is advisable to use each gene separately as a query. This approach, however, leaves the user with a tedious post-processing of partially redundant biclustering results. The fact that for each query-gene multiple parameter settings need to be tested in order to detect the ‘most optimal bicluster size’ adds to the redundancy problem. Results: To aid with this post-processing, we developed an ensemble approach to be used in combination with query-based biclustering. The method relies on a specifically designed consensus matrix in which the biclustering outcomes for multiple query-genes and for different possible parameter settings are merged in a statistically robust way. Clustering of this matrix results in distinct, non-redundant consensus biclusters that maximally reflect the information contained within the original query-based biclustering results. The usefulness of the developed approach is illustrated on a biological case study in Escherichia coli. Availability and implementation: Compiled Matlab code is available from http://homes.esat.kuleuven.be/~kmarchal/Supplementary_Information_DeSmet_2011/. Contact: kathleen.marchal@biw.kuleuven.be Supplementary information:Supplementary data are available at Bioinformatics online.

Summary: To facilitate the exploration of publicly available Zea mays expression data, we constructed a maize expression compendium, making use of an integration methodology and a consistent probe to gene mapping based on the 5b.60 sequence release of Z. mays. The compendium is made available through a web portal MAGIC that hosts a variety of analysis tools to easily browse and analyze the data. Our compendium is different from previous initiatives in combining expression values across different experiments by providing a consistent gene annotation across different platforms. Availability and implementation: http://bioinformatics.intec.ugent.be/magic/ Contact: kathleen.marchal@ugent.be Supplementary information: Supplementary data are available at Bioinformatics online.

Although it has largely dropped from sight today, The Family Expositor was culturally significant in its own time and much reprinted, from its publication in 1739 until the middle of the nineteenth century. An ambitious compendium of New Testament translation, paraphrase and commentary, it was conceived by its author, Philip Doddridge, as a learned work for family reading which would awaken and consolidate religious feeling. This article provides an account of the publication of The Family Expositor during Doddridge's lifetime and after his premature death in 1751, through an examination of his correspondence and especially that of his widow, to construct a picture of the collective editing, negotiating and marketing that went into the production of The Family Expositor .

Human Protein Reference Database (HPRD--http://www.hprd.org/), initially described in 2003, is a database of curated proteomic information pertaining to human proteins. We have recently added a number of new features in HPRD. These include PhosphoMotif Finder, which allows users to find the presence of over 320 experimentally verified phosphorylation motifs in proteins of interest. Another new feature is a protein distributed annotation system--Human Proteinpedia (http://www.humanproteinpedia.org/)--through which laboratories can submit their data, which is mapped onto protein entries in HPRD. Over 75 laboratories involved in proteomics research have already participated in this effort by submitting data for over 15,000 human proteins. The submitted data includes mass spectrometry and protein microarray-derived data, among other data types. Finally, HPRD is also linked to a compendium of human signaling pathways developed by our group, NetPath (http://www.netpath.org/), which currently contains annotations for several cancer and immune signaling pathways. Since the last update, more than 5500 new protein sequences have been added, making HPRD a comprehensive resource for studying the human proteome.

The authors are commended on a well-done review of instruments to assess cognitive functioning in pediatric psychology. The review follows the framework of a psychological assessment review, and it provides a concise compendium with good coverage of available tests and a compilation of their psychometric “vital statistics.” The article also goes beyond the tropes of routine review by identifying some themes and issues such as the potential value of having disorder specific (or other subgroup specific) norms. The choice of the words “evidence based” in the title invokes many associations, several perhaps unintended by the authors. For me, the phrase cued expectations developed from reading and teaching in an “Evidence-based Medicine” (EBM) framework (Guyatt & Rennie, 2002; Straus, Richardson, Glasziou, & Haynes, 2005). In this instance, my assumption was mistaken. However, as I read through the review, the mistake seems fortunate: it made me compare the methods we use to evaluate and describe evidence within the field of psychological assessment to the language and perspective that is evolving within EBM. Illuminating the discrepancies reveals many gaps that could be filled in ways that advance clinical practice as well as research. The structure of this commentary is as follows: first, I will address the numerous strengths of the review. There is much that is praiseworthy. Second, I will touch on the themes of short forms, retest intervals, and multigroup norms. These are important issues, and I believe that they have even more clinical relevance than indicated in the review. It is also likely that my recommendations may be different than what the authors would have provided if given the opportunity to expand their discussion of these issues. Third, I will briefly introduce EBM and sketch out some of the differences I see between EBA—the current approach within psychology—and EBM. Finally, I will close with suggestions for next steps in both clinical practice and research to assimilate some of the best features of both approaches.

Motivation: The increasing availability of gene expression microarray technology has resulted in the publication of thousands of microarray gene expression datasets investigating various biological conditions. This vast repository is still underutilized due to the lack of methods for fast, accurate exploration of the entire compendium.Results: We have collected Saccharomyces cerevisiae gene expression microarray data containing roughly 2400 experimental conditions. We analyzed the functional coverage of this collection and we designed a context-sensitive search algorithm for rapid exploration of the compendium. A researcher using our system provides a small set of query genes to establish a biological search context; based on this query, we weight each dataset's relevance to the context, and within these weighted datasets we identify additional genes that are co-expressed with the query set. Our method exhibits an average increase in accuracy of 273% compared to previous mega-clustering approaches when recapitulating known biology. Further, we find that our search paradigm identifies novel biological predictions that can be verified through further experimentation. Our methodology provides the ability for biological researchers to explore the totality of existing microarray data in a manner useful for drawing conclusions and formulating hypotheses, which we believe is invaluable for the research community.Availability: Our query-driven search engine, called SPELL, is available at http://function.princeton.edu/SPELLContact: ogt@genomics.princeton.eduSupplementary information: Several additional data files, figures and discussions are available at http://function.princeton.edu/SPELL/supplement

In conjunction with the largest solo retrospective of Jeff Wall's photographs to date, held at the Schaulager, Basel (30 April to 25 September 2005), a catalogue raisonne has been published in lieu of an exhibition catalogue. The very nature of this project, with its retrospective lens and view to historicise the past twenty-six years of Wall's career, offers a fresh opportunity for a lengthy consideration of his artistic practice. This book is not only a compendium of Wall's work and career, it was conceived and designed in collaboration with the artist and includes a number of his writings it is a book by Wall as much as a book on Wall. Like the ambitious Schaulager exhibition, the catalogue raisonne follows the years 1978-2004. The Destroyed Room, the picture considered by the artist to be the first to establish his mature artistic practice, was finished and

A critical component in the design of the Chemical Effects in Biological Systems (CEBS) Knowledgebase is a strategy to capture toxicogenomics study protocols and the toxicity endpoint data (clinical pathology and histopathology). A Study is generally an experiment carried out during a period of time for the purpose of obtaining data, and the Study Design Description captures the methods, timing, and organization of the Study. The CEBS Data Dictionary (CEBS-DD) has been designed to define and organize terms in an attempt to standardize nomenclature needed to describe a toxicogenomics Study in a structured yet intuitive format and provide a flexible means to describe a Study as conceptualized by the investigator. The CEBS-DD will organize and annotate information from a variety of sources, thereby facilitating the capture and display of toxicogenomics data in biological context in CEBS, i.e., associating molecular events detected in highly-parallel data with the toxicology/pathology phenotype as observed in the individual Study Subjects and linked to the experimental treatments. The CEBS-DD has been developed with a focus on acute toxicity studies, but with a design that will permit it to be extended to other areas of toxicology and biology with the addition of domain-specific terms. To illustrate the utility of the CEBS-DD, we present an example of integrating data from two proteomics and transcriptomics studies of the response to acute acetaminophen toxicity (A. N. Heinloth et al., 2004, Toxicol. Sci. 80, 193-202).

RNA interference (RNAi) is being used in large-scale genomic studies as a rapid way to obtain in vivo functional information associated with specific genes. How best to archive and mine the complex data derived from these studies provides a series of challenges associated with both the methods used to elicit the RNAi response and the functional data gathered. RNAiDB (RNAi Database; http://www. rnai.org) has been created for the archival, distribution and analysis of phenotypic data from large-scale RNAi analyses in Caenorhabditis elegans. The database contains a compendium of publicly available data and provides information on experimental methods and phenotypic results, including raw data in the form of images and streaming time-lapse movies. Phenotypic summaries together with graphical displays of RNAi to gene mappings allow quick intuitive comparison of results from different RNAi assays and visualization of the gene product(s) potentially inhibited by each RNAi experiment based on multiple sequence analysis methods. RNAiDB can be searched using combinatorial queries and using the novel tool PhenoBlast, which ranks genes according to their overall phenotypic similarity. RNAiDB could serve as a model database for distributing and navigating in vivo functional information from large-scale systematic phenotypic analyses in different organisms.

Schmidly, D. J., W. E. Tydeman, and A. L. Gardner (eds.). 2016. United States Biological Survey: A Compendium of its History, Personalities, Impacts, and Conflicts. Special Publications, Museum of Texas Tech University, Lubbock, Vol. 64, ix + 124 pp. ISBN 1-929330-28-6, price (hard cover), $24.95. In 2013, David Schmidly gave a talk at the ASM meeting on the life and career of Vernon Bailey, one of the most productive and well-known biologist with the United States Biological Survey (Survey—Schmidly 2013). This was sufficiently well received that Schmidly was invited to organize a symposium the following year that expanded the theme to address the role and influence of the Survey on natural history in North America (Schmidly and Gardner 2014). This also was well received and subsequently prepared as a series of chapters in the volume under review here. I asked to provide this unsolicited review … Department of Wildlife, Fish, and Conservation Biology, University of California, Davis, Davis, CA 95616, USA; e-mail: dakelt{at}ucdavis.edu

The practice of detecting and enumerating all oxidase-negative, glucose-fermenting-Gram-negative rods (i.e., the family Enterobacteriaceae) isused to indicate unsanitary or inadequate food processing conditions. The objective of this interlaboratory collaborative study was to evaluate and compare the methods described in Standard Methods for the Examination of Dairy Products (SMEDP) and the Compendium of Methods for the Microbiological Examination of Foods (Compendium) with a commercial product, the 3M™ Petrifilm™ Enterobacteriaceae Count Plate, for the recovery of Enterobacteriaceae in foods. Six foods—cheddar cheese, milk, flour, frozen prepared meals, frozen broccoli, and nut pieces—were analyzed for Enterobacteriaceae by 12 collaborating laboratories. For each food tested, the collaborators received 8 blind test portions consisting of a control test portion and 3 levels of inoculated test portion, each in duplicate. Each test portion was tested by the Petrifilm Enterobacteriaceae Count Plate method as well as the SMEDP or Compendium methods. The precision estimates (repeat-ability or within-laboratory variation, and reproducibility or between-laboratory variation) were calculated with standard statistical techniques.

In their reviews of the study of cervical radiofrequency neurotomy (RFN) by MacVicar, Borowczyk et al. [1], some of the referees raised questions that were not critical of the internal validity of the study but which pertained to its external validity. In essence, these questions concerned the context of the study and differences between New Zealand and the United States with respect to patients and medical practices. Conventionally, such questions would be answered in a covering letter to the satisfaction of the Editor. However, in the present case, the questions and answers contained information that would be of wider interest beyond the peer-review process. That information serves not only to elaborate and explain the study of MacVicar, Borowczyk et al. [1], but also to underscore the wider relevance of stringent standards of practice. For that reason, we have composed this letter to serve as a compendium to the published article. It provides answers to several of the key questions raised in the review process. At the time that the study was commenced, New Zealand was in a unique position. RFN was not practiced, was not available to patients, and was not reimbursed. In one sense, New Zealand was behind the rest of the world, but in another sense it had not been polluted with disparate methods of RFN of unknown efficacy. When a small group of practitioners wanted to make RFN available, the opportunity arose to do it well, and avoid mistakes made elsewhere in the world. The senior medical advisor of the single insurance company that covers accident compensation in New Zealand faced a dilemma. There was no universally accepted technique for cervical RFN, and no consistent protocol. Various Dutch, German, and other protocols had been found wanting [2], and their outcomes were not impressive. Consequently, …

The SCOP (Structural Classification of Proteins) database is a comprehensive ordering of all proteins of known structure, according to their evolutionary and structural relationships. Protein domains in SCOP are grouped into species and hierarchically classified into families, superfamilies, folds and classes. Recently, we introduced a new set of features with the aim of standardizing access to the database, and providing a solid basis to manage the increasing number of experimental structures expected from structural genomics projects. These features include: a new set of identifiers, which uniquely identify each entry in the hierarchy; a compact representation of protein domain classification; a new set of parseable files, which fully describe all domains in SCOP and the hierarchy itself. These new features are reflected in the ASTRAL compendium. The SCOP search engine has also been updated, and a set of links to external resources added at the level of domain entries. SCOP can be accessed at http://scop.mrc-lmb.cam.ac.uk/scop.

The ASTRAL compendium provides several databases and tools to aid in the analysis of protein structures, particularly through the use of their sequences. It is partially derived from the SCOP database of protein domains, and it includes sequences for each domain as well as other resources useful for studying these sequences and domain structures. Several major improvements have been made to the ASTRAL compendium since its initial release 2 years ago. The number of protein domain sequences included has doubled from 15 190 to 30 867, and additional databases have been added. The Rapid Access Format (RAF) database contains manually curated mappings linking the biological amino acid sequences described in the SEQRES records of PDB entries to the amino acid sequences structurally observed (provided in the ATOM records) in a format designed for rapid access by automated tools. This information is used to derive sequences for protein domains in the SCOP database. In cases where a SCOP domain spans several protein chains, all of which can be traced back to a single genetic source, a ‘genetic domain’ sequence is created by concatenating the sequences of each chain in the order found in the original gene sequence. Both the original-style library of SCOP sequences and a new library including genetic domain sequences are available. Selected representative subsets of each of these libraries, based on multiple criteria and degrees of similarity, are also included. ASTRAL may be accessed at http://astral.stanford.edu/.

Participant-rated and compendium-coded intensity of daily physical activities were compared in 148 African American, 144 Native American, 51 non-Hispanic White women ages 40 to 91 years who completed 4 days of activity records. For compendium-coded intensity, reported activities were classified as light (3 metabolic equivalents [METS]), moderate (3-6 METS), or vigorous (6 METS) using the Compendium of Physical Activities (1), whereas these categories were self-assigned for participant-rated intensity. Minutes per day (min/d) spent in activities at each intensity level were computed. Relative to compendium-coded min/d, participants reported significantly greater time spent in light (+10 min/d; p.01) and vigorous (+17 min/d; p.001) activities, and less time spent in moderate activities (-27 min/d; p.001). Similarly, compendium-coded estimates yielded higher rates ofparticipants meeting Centersfor Disease Control and Prevention-American College of Sports Medicine and Surgeon General recommendations than participant-rated estimates (11-18% differences) but substantially lower rates meeting American College of Sports Medicine vigorous recommendations (22% difference). Further, 247 greater kilocalories per day were estimated based on compendium-coded intensity. Kilocalories per day estimates based on compendium codings were more highly associated with pedometer counts than those based on participant ratings (p.05). Studypatterns were generally seen across all sample subgroups. Discrepancies between participant and compendium estimates are likely to be most meaningful in studies estimating energy expenditure as it relates to health outcomes and in studies estimating vigorous activities.

With systematic sequencing efforts on the human and other model organisms in full swing, a tremendous flood of sequence data is being produced at breakneck speed. Considering the Human Genome Project alone, it is currently estimated that over 2 million bases are deposited into GenBank each day. This growth will only accelerate in the future, given the new goal of having a working draft covering 90% of the genome by the spring of 2000 and the complete sequence in-hand in 2002 (1). When considering all organismal sequencing efforts together, it immediately becomes obvious that there must be concrete and coherent plans in place to both warehouse and access these data, data which will become more and more important as we enter into an era of sequence-based biology. The most recent five-year plan for the Human Genome Project (1) recognizes the importance of the connection between the in silico world and the bench, and has put forth recommendations regarding bioinformatics and computational biology, particularly with respect to databases and the development of analytical tools. Databases that grow out of the human and other systematic sequencing efforts should not be just storehouses for thousands of bases or amino acids; rather, they need to make logical connections to other types of information that are available, such as phenotypic or expression data, as these types of connections serve to increase the intrinsic value of the raw sequence data, allowing for biological discovery. Of particular importance will be the curation and annotation of specialized databases, which will help to ensure data quality as well as foster the ability to access and analyze sequence data. Many such specialized databases have emerged over the years, and this journal has devoted its first issue over the last several years to documenting the availability and features of these databases. With the current issue, Nucleic Acids Research will be facilitating access to these databases online through a new entity called the Molecular Biology Database Collection. By doing so, it is hoped that individual investigators will be able to more easily find and use specialized databases that are appropriate to their scientific needs. The initial set of databases included in the online compilation, available at http://www.oup.co.uk/nar/Volume_28/Issue_01/html/gkd115_gml.html, is shown in Table ​Table1.1. The list includes databases for which there are full-length descriptions in the current issue, as well as other databases which represent a valuable resource to the biological community. Also included are databases collected by Christian Burks as part of the 1999 Database Issue (2). Efforts have been made to reduce redundancy in the list with respect to content wherever possible. An emphasis has also been placed on including databases where new value is added to the underlying data by virtue of curation, new data connections, or other innovative approaches. While Table ​Table11 attempts to classify these databases by type, it is often true that these databases are more global in nature, providing multiple types of information. Links to these databases will be updated regularly. Suggestions for the inclusion of additional database resources in this online compendium are encouraged and may be directed to the author (andy@nhgri.nih.gov). Table 1. Molecular Biology Database Collection

ADepartment of Energy report released in 1987 stated in a visionary prediction that “Knowledge of the human genome is as necessary to the continuing progress of medicine and other health sciences as knowledge of human anatomy has been for the present state of medicine” (Barnhart 1989). The pursuit of this knowledge has marked an era of rapid genomics-based discovery that continues to yield unique insights into connections between disease and molecular factors. One key method for transforming these initial insights into direct evidence of disease pathogenesis is molecular imaging. Imaging techniques that have been customized for laboratory animals provide scientists with the unprecedented ability to link detailed molecular understanding with the complexity of whole organism physiological responses and anatomical detail. The advancement of knowledge derived from the mammalian genome is likely to depend on the context provided by the unique blending of our knowledge of anatomy with the translational application of imaging technology. The primary objective of this ILAR Journal issue focused on laboratory animal imaging is to provide readers with a compendium of reviews that describe the methods, the limitations, and a few examples of the most common applications of small animal imaging to human disease. Because most disease processes are dynamic, there are inherent limitations to using static tissue-based techniques to study dynamic processes. Among these is that a large number of animals is needed for every experiment to enable the processing of tissue at given time points of interest, and histopathological examination of these tissues using standard microscopy is a daunting task. In addition, there is a degree of variability introduced when the control level of a factor is determined by comparing different animals instead of using each animal as its own control. Experimental designs of longitudinal studies pose particular limitations because a certain degree of understanding about the kinetics of a disease process is critical to the appropriate timing of tissue collections. The imaging modalities available for use with laboratory animals provide a means to explore the molecular mechanism of several diseases, minimize many of the limitations of static tissue-based techniques, and, most importantly, decrease the numbers of animals required. In fact, depending on the application, it is possible to reduce the number of animals required per study by as much as 80% to 90%. This feature is noteworthy because, perhaps unique to the ILAR Journal, there is an intentional effort to publish reviews that include considerations specifically relevant to animal care and use. The first article, by Brenda Klaunberg and Judith Davis, presents an overview of key considerations for laboratory animal imaging center design. This review not only is relevant to readers considering new facility design but also can provide a series of quick checks for existing centers as well as strategies for improvement. Contributing authors Isabel Hildebrandt, Helen Su, and Wolfgang Weber then discuss anesthesia for in vivo imaging of small animals in the context of how animal preparation differs among imaging modalities, and how the imaging procedures themselves can affect animal physiology. A general overview of practical considerations in rodent cardiac imaging is provided by Kennita Johnson as a segue to detailed reviews of specific imaging techniques. This article is a good source of baseline information about the particular challenges of cardiac imaging. The contributions of imaging technology to the biomedical sciences are incontrovertible. In fact, one has only to list the number of Nobel prizes awarded to scientists in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) to appreciate the importance and recognition this field has received. These include the 2003 Nobel Prize for Physiology and Medicine awarded to Paul Lauterbur and Peter Mansfield for the development of MRI. Earlier NMRrelated Nobel Prizes were awarded for Chemistry (Kurt Wuthrich in 2002, Richard R. Ernst in 1991) and Physics (Felix Bloch and Edward M. Purcell in 1952 and Isidor I. Rabi in 1944; http://nobelprize.org). The first manuscript describing the MRI of a rat was published almost 25 years ago, and the technique continues to evolve and expand the scientific advances made possible Myrtle A. Davis, DVM, PhD, is a Research Advisor in Toxicology, Drug Disposition, and Pharmacokinetics at Lilly Research Laboratories in Greenfield, Indiana. Address correspondence and reprint requests to Dr. Myrtle Davis, Toxicology, Drug Disposition, and Pharmacokinetics, Lilly Research Laboratories, 2001 W. Main Street, Greenfield, IN 46140 or email davisma@lilly.com.

J. Regan Thomas, ed. Facial Plastic Surgery Clinics of North America: Multicultural Aesthetics in Facial Plastic Surgery . Hardcover, Publisher: Elsevier; 1 edition (August 7, 2014). Language: English; ISBN-10: 0323320112; ISBN-13: 978-0323320115; Pages: 149, Price: $99.00. ![Graphic][1] As with many things in life, context is very important. In reviewing this issue of Facial Plastic Surgery Clinics it would be unfair not to point out that these 12 chapters form part of an ongoing compendium in a series that has been compiled over the last 15 years. In its entirety it provides a comprehensive resource of literature for facial reconstruction and aesthetics. The theme of this issue is the special considerations of ethnicity in relation to facial plastic surgery and the areas focus as one might expect on rhinoplasty and Asian blepharoplasty. There are thoughtful introductory chapters, particularly one written by Julian Rowe-Jones, in which he discusses the importance of managing expectations not just from an aesthetic and psychological viewpoint but minding the context of cultural background. The issue also includes two general introductory chapters, some chapters on hair restoration and skin … Corresponding Author: Dr Norman Waterhouse, 150 Harley Street, London W1G 7LQ, United Kingdom. E-mail: info{at}nwal.co.uk [1]: /embed/inline-graphic-1.gif

Comprehensive disease classification, integration and annotation are crucial for biomedical discovery. At present, disease compilation is incomplete, heterogeneous and often lacking systematic inquiry mechanisms. We introduce MalaCards, an integrated database of human maladies and their annotations, modeled on the architecture and strategy of the GeneCards database of human genes. MalaCards mines and merges 44 data sources to generate a computerized card for each of 16 919 human diseases. Each MalaCard contains disease-specific prioritized annotations, as well as inter-disease connections, empowered by the GeneCards relational database, its searches and GeneDecks set analyses. First, we generate a disease list from 15 ranked sources, using disease-name unification heuristics. Next, we use four schemes to populate MalaCards sections: (i) directly interrogating disease resources, to establish integrated disease names, synonyms, summaries, drugs/therapeutics, clinical features, genetic tests and anatomical context; (ii) searching GeneCards for related publications, and for associated genes with corresponding relevance scores; (iii) analyzing disease-associated gene sets in GeneDecks to yield affiliated pathways, phenotypes, compounds and GO terms, sorted by a composite relevance score and presented with GeneCards links; and (iv) searching within MalaCards itself, e.g. for additional related diseases and anatomical context. The latter forms the basis for the construction of a disease network, based on shared MalaCards annotations, embodying associations based on etiology, clinical features and clinical conditions. This broadly disposed network has a power-law degree distribution, suggesting that this might be an inherent property of such networks. Work in progress includes hierarchical malady classification, ontological mapping and disease set analyses, striving to make MalaCards an even more effective tool for biomedical research. Database URL: http://www.malacards.org/

For many years algorithms were taught exclusively to computer scientists, with relatively few students from other disciplines attending algorithms courses. A biology student in an algorithms class would be a surprising and unlikely (though not entirely unwelcome) guest in the 1990s. Things change; some biology students now take some sort of Algorithms 101. At the same time, curious computer science students often take Genetics 101. Here comes an important question of how to teach bioinformatics in the 21st century. Will we teach bioinformatics to future biology students as a collection of cookbook style recipes or as a computational science that first explain ideas and builds on applications afterwards? This is particularly important at the time when bioinformatics courses may soon become required for all graduate biology students in leading universities. Not to mention that some universities have already started undergraduate bioinformatics programs and the discussions are underway about adding new computational courses to the standard undergraduate biology curriculum a dramatic paradigm shift in biology education. Since bioinformatics is a computational science, a bioinformatics course should strive to present the principles and ideas that drive an algorithm’s design or explain a crux of a statistical approach, rather than to be a stamp-collection of the algorithms and statistical techniques themselves. Many existing bioinformatics books and courses reduce bioinformatics to a compendium of computational protocols without even trying to explain the computational ideas that drove the development of bioinformatics in the last 30 years. Other books (written by computer scientists for computer scientists) try to explain bioinformatics ideas at the level that is well above the computational level of most biologists. These books often fail to connect the computational ideas and applications thus reducing a biologist’s motivation to invest time and effort into such a book. We feel that focusing on ideas has more intellectual value and represents a long-term investment: protocols change quickly, but the computational ideas don’t seem to. However, the question of how to deliver these ideas