Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Investigating extradomiciliary transmission of tuberculosis: An exploratory approach using social network patterns of TB cases and controls and the genotyping of Mycobacterium tuberculosis

Extradomiciliary contacts have been overlooked in the study of TB transmission due to difficulties in identifying actual contacts in large populations. Complex network analysis provides a framework to model the structure of contacts, specially extradomiciliary ones. We conducted a study of incident sputum-positive TB cases and healthy controls occurring in a moderate TB burden city. Cases and controls were interviewed to obtain data regarding the usual locations of residence, work, study, and leisure. Mycobacterium tuberculosis isolated from sputum was genotyped. The collected data were used to build networks based on a framework of putative social interactions indicating possible TB transmission. A user-friendly open source environment (GraphTube) was setup to extract information from the collected data. Networks based on the likelihood of patient-patient, patient-healthy, and healthy-healthy contacts were setup, depending on a constraint of geographical distance of places attended by the volunteers. Using a threshold for the geographical distance of 300 m, the differences between TB cases and controls are revealed. Several clusters formed by social network nodes with high genotypic similarity were characterized. The developed framework provided consistent results and can be used to support the targeted search of potentially infected individuals and to help to understand the TB transmission

Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages

Background: Approximately 10 % of the Mycobacterium tuberculosis genome is made up of two families of genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE and PPE families are typified by their highly conserved N-terminal domains that incorporate proline-glutamate (PE) and proline-proline-glutamate (PPE) signature motifs. They are hypothesised to be important virulence factors involved with host-pathogen interactions, but their high genetic variability and complexity of analysis means they are typically disregarded in genome studies. Results: To elucidate the structure of these genes, 518 genomes from a diverse international collection of clinical isolates were de novo assembled. A further 21 reference M. tuberculosis complex genomes and long read sequence data were used to validate the approach. SNP analysis revealed that variation in the majority of the 168 pe/ppe genes studied was consistent with lineage. Several recombination hotspots were identified, notably pe_pgrs3 and pe_pgrs17. Evidence of positive selection was revealed in 65 pe/ppe genes, including epitopes potentially binding to major histocompatibility complex molecules. Conclusions: This, the first comprehensive study of the pe and ppe genes, provides important insight into M. tuberculosis diversity and has significant implications for vaccine development

Heme Oxygenase-1 Regulation of Matrix Metalloproteinase-1 Expression Underlies Distinct Disease Profiles in Tuberculosis

Andrade, Bruno de Bezerril; Bessa, Theolis Costa Barbosa. Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Unidade de Medicina Investigativa. Laboratório Integrado de Microbiologia e Imunorregulação. Salvador, BA, Brasil *Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; †Unidade de Medicina Investigativa, Laborato´rio Integrado de Microbiologia e Imunorregulação, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Brazil; ‡National Institutes of Health, International Center for Excellence in Research, Chennai 600031, India; xNational Institute for Research in Tuberculosis, Chennai 600031, India; {Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; ‖Department of Medicine, Imperial College London, London SW7 2AZ, United Kingdom; #Government Stanley Medical Hospital, Chennai 600001, India; **Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; ††Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; ‡‡Division of Intramural Research, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD 20892; xxClinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; {{T-Lymphocyte Biology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; ‖‖Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-07-21T17:34:59Z No. of bitstreams: 1 Andrade BB Heme oxygenase-1 regulation....pdf: 3477535 bytes, checksum: 060069be6b5ca6497c330534a63ac8a0 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-07-21T17:57:14Z (GMT) No. of bitstreams: 1 Andrade BB Heme oxygenase-1 regulation....pdf: 3477535 bytes, checksum: 060069be6b5ca6497c330534a63ac8a0 (MD5)Made available in DSpace on 2017-07-21T17:57:14Z (GMT). No. of bitstreams: 1 Andrade BB Heme oxygenase-1 regulation....pdf: 3477535 bytes, checksum: 060069be6b5ca6497c330534a63ac8a0 (MD5) Previous issue date: 2015Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. J.M., V.C.M., and J.R.F. were supported by the National Heart, Lung, and Blood Institute Intramural Research Program. The Brazilian study was funded by Fundação de Amparo à Pesquisa do Estado da Bahia and Conselho Nacional de Desenvolvimento Cientı´fico e Tecnológico, Brazil (Grant 028/2010).Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Unidade de Medicina Investigativa. Laboratório Integrado de Microbiologia e Imunorregulação. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Unidade de Medicina Investigativa. Laboratório Integrado de Microbiologia e Imunorregulação. Salvador, BA, BrasilMúltipla – ver em NotasPulmonary tuberculosis (TB) is characterized by oxidative stress and lung tissue destruction by matrix metalloproteinases (MMPs). The interplay between these distinct pathological processes and the implications for TB diagnosis and disease staging are poorly understood. Heme oxygenase-1 (HO-1) levels were previously shown to distinguish active from latent TB, as well as successfully treated Mycobacterium tuberculosis infection. MMP-1 expression is also associated with active TB. In this study, we measured plasma levels of these two important biomarkers in distinct TB cohorts from India and Brazil. Patients with active TB expressed either very high levels of HO-1 and low levels of MMP-1 or the converse. Moreover, TB patients with either high HO-1 or MMP-1 levels displayed distinct clinical presentations, as well as plasma inflammatory marker profiles. In contrast, in an exploratory North American study, inversely correlated expression of HO-1 and MMP-1 was not observed in patients with other nontuberculous lung diseases. To assess possible regulatory interactions in the biosynthesis of these two enzymes at the cellular level, we studied the expression of HO-1 and MMP-1 in M. tuberculosis-infected human and murine macrophages. We found that infection of macrophages with live virulent M. tuberculosis is required for robust induction of high levels of HO-1 but not MMP-1. In addition, we observed that CO, a product of M. tuberculosis-induced HO-1 activity, inhibits MMP-1 expression by suppressing c-Jun/AP-1 activation. These findings reveal a mechanistic link between oxidative stress and tissue remodeling that may find applicability in the clinical staging of TB patients

Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosisMycobacterium\ tuberculosis

International audienceTo characterize the genetic determinants of resistance to antituberculosis drugs, we performed a genome-wide association study (GWAS) of 6,465 $Mycobacterium\ tuberculosis$ clinical isolates from more than 30 countries. A GWAS approach within a mixed-regression framework was followed by a phylogenetics-based test for independent mutations. In addition to mutations in established and recently described resistance-associated genes, novel mutations were discovered for resistance to cycloserine, ethionamide and para-aminosalicylic acid. The capacity to detect mutations associated with resistance to ethionamide, pyrazinamide, capreomycin, cycloserine and para-aminosalicylic acid was enhanced by inclusion of insertions and deletions. Odds ratios for mutations within candidate genes were found to reflect levels of resistance. New epistatic relationships between candidate drug-resistance-associated genes were identified. Findings also suggest the involvement of efflux pumps ($drrA$ and $Rv2688c$) in the emergence of resistance. This study will inform the design of new diagnostic tests and expedite the investigation of resistance and compensatory epistatic mechanisms