Constructing a semantic predication gold standard from the biomedical literature

<p>Abstract</p> <p>Background</p> <p>Semantic relations increasingly underpin biomedical text mining and knowledge discovery applications. The success of such practical applications crucially depends on the quality of extracted relations, which can be assessed against a gold standard reference. Most such references in biomedical text mining focus on narrow subdomains and adopt different semantic representations, rendering them difficult to use for benchmarking independently developed relation extraction systems. In this article, we present a multi-phase gold standard annotation study, in which we annotated 500 sentences randomly selected from MEDLINE abstracts on a wide range of biomedical topics with 1371 semantic predications. The UMLS Metathesaurus served as the main source for conceptual information and the UMLS Semantic Network for relational information. We measured interannotator agreement and analyzed the annotations closely to identify some of the challenges in annotating biomedical text with relations based on an ontology or a terminology.</p> <p>Results</p> <p>We obtain fair to moderate interannotator agreement in the practice phase (0.378-0.475). With improved guidelines and additional semantic equivalence criteria, the agreement increases by 12% (0.415 to 0.536) in the main annotation phase. In addition, we find that agreement increases to 0.688 when the agreement calculation is limited to those predications that are based only on the explicitly provided UMLS concepts and relations.</p> <p>Conclusions</p> <p>While interannotator agreement in the practice phase confirms that conceptual annotation is a challenging task, the increasing agreement in the main annotation phase points out that an acceptable level of agreement can be achieved in multiple iterations, by setting stricter guidelines and establishing semantic equivalence criteria. Mapping text to ontological concepts emerges as the main challenge in conceptual annotation. Annotating predications involving biomolecular entities and processes is particularly challenging. While the resulting gold standard is mainly intended to serve as a test collection for our semantic interpreter, we believe that the lessons learned are applicable generally.</p

Searches for Long Lived Neutral Particles

An intriguing possibility for TeV scale physics is the existence of neutral long lived particles (LOLIPs) that subsequently decay into SM states. Such particles are many cases indistinguishable from missing transverse energy (MET) at colliders. We propose new methods to search for these particles using neutrino telescopes. We study their detection prospects, assuming production either at the LHC or through dark matter (DM) annihilations in the Sun and the Earth. We find that the sensitivity for LOLIPs produced at the LHC is limited by luminosity and detection energy thresholds. On the other hand, in the case of DM annihilation into LOLIPs, the sensitivity of neutrino telescopes is promising and may extend beyond the reach of upcoming direct detection experiments. In the context of low scale hidden sectors weakly coupled to the SM, such indirect searches allow to probe couplings as small as 10^-15.Comment: 22 pages, 6 figure

Low-Energy Signals from Kinetic Mixing with a Warped Abelian Hidden Sector

We investigate the detailed phenomenology of a light Abelian hidden sector in the Randall-Sundrum framework. Relative to other works with light hidden sectors, the main new feature is a tower of hidden Kaluza-Klein vectors that kinetically mix with the Standard Model photon and Z. We investigate the decay properties of the hidden sector fields in some detail, and develop an approach for calculating processes initiated on the ultraviolet brane of a warped space with large injection momentum relative to the infrared scale. Using these results, we determine the detailed bounds on the light warped hidden sector from precision electroweak measurements and low-energy experiments. We find viable regions of parameter space that lead to significant production rates for several of the hidden Kaluza-Klein vectors in meson factories and fixed-target experiments. This offers the possibility of exploring the structure of an extra spacetime dimension with lower-energy probes.Comment: (1+32) Pages, 13 Figures. v2: JHEP version (minor modifications, results unchanged

Corpus annotation for mining biomedical events from literature

<p>Abstract</p> <p>Background</p> <p>Advanced Text Mining (TM) such as semantic enrichment of papers, event or relation extraction, and intelligent Question Answering have increasingly attracted attention in the bio-medical domain. For such attempts to succeed, text annotation from the biological point of view is indispensable. However, due to the complexity of the task, semantic annotation has never been tried on a large scale, apart from relatively simple term annotation.</p> <p>Results</p> <p>We have completed a new type of semantic annotation, event annotation, which is an addition to the existing annotations in the GENIA corpus. The corpus has already been annotated with POS (Parts of Speech), syntactic trees, terms, etc. The new annotation was made on half of the GENIA corpus, consisting of 1,000 Medline abstracts. It contains 9,372 sentences in which 36,114 events are identified. The major challenges during event annotation were (1) to design a scheme of annotation which meets specific requirements of text annotation, (2) to achieve biology-oriented annotation which reflect biologists' interpretation of text, and (3) to ensure the homogeneity of annotation quality across annotators. To meet these challenges, we introduced new concepts such as Single-facet Annotation and Semantic Typing, which have collectively contributed to successful completion of a large scale annotation.</p> <p>Conclusion</p> <p>The resulting event-annotated corpus is the largest and one of the best in quality among similar annotation efforts. We expect it to become a valuable resource for NLP (Natural Language Processing)-based TM in the bio-medical domain.</p

Intratumoral IL-12 and TNF-α–Loaded Microspheres Lead To Regression of Breast Cancer and Systemic Antitumor Immunity

Background: Local, sustained delivery of cytokines at a tumor can enhance induction of antitumor immunity and may be a feasible neoadjuvant immunotherapy for breast cancer. We evaluated the ability of intratumoral poly-lactic-acid-encapsulated microspheres (PLAM) containing interleukin 12 (IL-12), tumor necrosis factor α (TNF-α), and granulocyte-macrophage colony stimulating factor (GM-CSF) in a murine model of breast cancer to generate a specific antitumor response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41401/1/10434_2004_Article_147.pd

Direct Type I IFN but Not MDA5/TLR3 Activation of Dendritic Cells Is Required for Maturation and Metabolic Shift to Glycolysis after Poly IC Stimulation

We thank the Rockefeller University Center for Clinical and Translational Science (UL1 TR000043 NCATS, NIH) for technical support

Text Mining Improves Prediction of Protein Functional Sites

We present an approach that integrates protein structure analysis and text mining for protein functional site prediction, called LEAP-FS (Literature Enhanced Automated Prediction of Functional Sites). The structure analysis was carried out using Dynamics Perturbation Analysis (DPA), which predicts functional sites at control points where interactions greatly perturb protein vibrations. The text mining extracts mentions of residues in the literature, and predicts that residues mentioned are functionally important. We assessed the significance of each of these methods by analyzing their performance in finding known functional sites (specifically, small-molecule binding sites and catalytic sites) in about 100,000 publicly available protein structures. The DPA predictions recapitulated many of the functional site annotations and preferentially recovered binding sites annotated as biologically relevant vs. those annotated as potentially spurious. The text-based predictions were also substantially supported by the functional site annotations: compared to other residues, residues mentioned in text were roughly six times more likely to be found in a functional site. The overlap of predictions with annotations improved when the text-based and structure-based methods agreed. Our analysis also yielded new high-quality predictions of many functional site residues that were not catalogued in the curated data sources we inspected. We conclude that both DPA and text mining independently provide valuable high-throughput protein functional site predictions, and that integrating the two methods using LEAP-FS further improves the quality of these predictions

IL-12 and GM-CSF in DNA/MVA Immunizations against HIV-1 CRF12_BF Nef Induced T-Cell Responses With an Enhanced Magnitude, Breadth and Quality

In Argentina, the HIV epidemic is characterized by the co-circulation of subtype B and BF recombinant viral variants. Nef is an HIV protein highly variable among subtypes, making it a good tool to study the impact of HIV variability in the vaccine design setting. We have previously reported a specific cellular response against NefBF with low cross-reactivity to NefB in mice. The aim of this work was to analyze whether the co-administration of IL-12 and GM-CSF, using DNA and MVA vaccine vectors, could improve the final cellular response induced. Mice received three DNA priming doses of a plasmid that express NefBF plus DNAs expressing IL-12 and/or GM-CSF. Afterwards, all the groups were boosted with a MVAnefBF dose. The highest increase in the magnitude of the NefBF response, compared to that induced in the control was found in the IL-12 group. Importantly, a response with higher breadth was detected in groups which received IL-12 or GM-CSF, evidenced as an increased frequency of recognition of homologous (BF) and heterologous (B) Nef peptides, as well as a higher number of other Nef peptide pools representing different viral subtypes. However, these improvements were lost when both DNA cytokines were simultaneously administered, as the response was focused against the immunodominant peptide with a detrimental response towards subdominant epitopes. The pattern of cytokines secreted and the specific-T-cell proliferative capacity were improved in IL-12 and IL-12+GM-CSF groups. Importantly IL-12 generated a significant higher T-cell avidity against a B heterologous peptide

CD4saurus Rex &HIVelociraptor vs. development of clinically useful immunological markers: a Jurassic tale of frozen evolution

One of the most neglected areas of everyday clinical practice for HIV physicians is unexpectedly represented by CD4 T cell counts when used as an aid to clinical decisions. All who care for HIV patients believe that CD4+ T cell counts are a reliable method to evaluate a patient immune status. There is however a fatalistic acceptance that besides its general usefulness, CD4+ T cell counts have relevant clincal and immunological limits. Shortcomings of CD4 counts appear in certain clinical scenarios including identification of immunological nonresponders, subsequent development of cancer on antiretroviral teatment, failure on tretment simplification. Historical and recently described parameters might be better suited to advise management of patients at certain times during their disease history. Immunogenotypic parameters and innate immune parameters that define progression as well as immune parameters associated with immune recovery are available and have not been introduced into validation processes in larger trials. The scientific and clinical community needs an effort in stimulating clinical evolution of immunological tests beyond "CD4saurus Rex" introducing new parameters in the clinical arena after appropriate validatio