Enriching a biomedical event corpus with meta-knowledge annotation

Background: Biomedical papers contain rich information about entities, facts and events of biological relevance. To discover these automatically, we use text mining techniques, which rely on annotated corpora for training. In order to extract protein-protein interactions, genotype-phenotype/gene-disease associations, etc., we rely on event corpora that are annotated with classified, structured representations of important facts and findings contained within text. These provide an important resource for the training of domain-specific information extraction (IE) systems, to facilitate semantic-based searching of documents. Correct interpretation of these events is not possible without additional information, e.g., does an event describe a fact, a hypothesis, an experimental result or an analysis of results? How confident is the author about the validity of her analyses? These and other types of information, which we collectively term meta-knowledge, can be derived from the context of the event.Results: We have designed an annotation scheme for meta-knowledge enrichment of biomedical event corpora. The scheme is multi-dimensional, in that each event is annotated for 5 different aspects of meta-knowledge that can be derived from the textual context of the event. Textual clues used to determine the values are also annotated. The scheme is intended to be general enough to allow integration with different types of bio-event annotation, whilst being detailed enough to capture important subtleties in the nature of the meta-knowledge expressed in the text. We report here on both the main features of the annotation scheme, as well as its application to the GENIA event corpus (1000 abstracts with 36,858 events). High levels of inter-annotator agreement have been achieved, falling in the range of 0.84-0.93 Kappa.Conclusion: By augmenting event annotations with meta-knowledge, more sophisticated IE systems can be trained, which allow interpretative information to be specified as part of the search criteria. This can assist in a number of important tasks, e.g., finding new experimental knowledge to facilitate database curation, enabling textual inference to detect entailments and contradictions, etc. To our knowledge, our scheme is unique within the field with regards to the diversity of meta-knowledge aspects annotated for each event. © 2011 Thompson et al; licensee BioMed Central Ltd

Epigenetic modulators of B cell fate identified through coupled phenotype-transcriptome analysis

High-throughput methodologies are the cornerstone of screening approaches to identify novel compounds that regulate immune cell function. To identify novel targeted therapeutics to treat immune disorders and haematological malignancies, there is a need to integrate functional cellular information with the molecular mechanisms that regulate changes in immune cell phenotype. We facilitate this goal by combining quantitative methods for dissecting complex simultaneous cell phenotypic effects with genomic analysis. This combination strategy we term Multiplexed Analysis of Cells sequencing (MAC-seq), a modified version of Digital RNA with perturbation of Genes (DRUGseq). We applied MAC-seq to screen compounds that target the epigenetic machinery of B cells and assess altered humoral immunity by measuring changes in proliferation, survival, differentiation and transcription. This approach revealed that polycomb repressive complex 2 (PRC2) inhibitors promote antibody secreting cell (ASC) differentiation in both murine and human B cells in vitro. This is further validated using T cell-dependent immunization in mice. Functional dissection of downstream effectors of PRC2 using arrayed CRISPR screening uncovered novel regulators of B cell differentiation, including Mybl1, Myof, Gas7 and Atoh8. Together, our findings demonstrate that integrated phenotype-transcriptome analyses can be effectively combined with drug screening approaches to uncover the molecular circuitry that drives lymphocyte fate decisions

Feasibility of objectively measured physical activity and sedentary behavior in patients with malignant pleural effusion

Purpose: Malignant pleural effusion (MPE) affects 1 million people worldwide annually and can significantly impair physical activity. Accelerometry is a validated method of objectively assessing physical activity. The purpose of this study was to determine the compliance in patients with MPE to accelerometry and describe their activity. Methods: Patients with MPE wore an Actigraph GT3X accelerometer over a 7-day continuous wear protocol. Compliance was measured as the percent of patients who had =4 valid days (i.e., 8-h/day of waking wear-time). Eastern Cooperative Oncology Group performance status was documented the day of actigraphy initialization. Results: Forty-six patients with MPE received accelerometers; 44 (95.7%) returned their device. No complications were reported on their use. Forty subjects (90.9%) had =4 valid days of wear-time. Patients spent most of their waking hours sedentary [mean 11.0 h (SD 1.95)], with limited participation in moderate and vigorous physical activity [mean 9.5 min (SD 14.16)]. Compared to patients with better performance status (n = 32), patients with poorer performance status (n = 11) spent significantly more hours/day sedentary [mean difference 2.1 (CI 0.86–3.32); p = 0.001], as did those who survived <3 months (n = 5) compared to >12 months (n = 27) [mean difference 2.6 (CI 0.49–4.77); p = 0.013). Conclusion: Accelerometry was applied successfully in patients with MPE with high compliance and no adverse events. This is the first reported objectively measured physical activity in patients with MPE and revealed high sedentary behavior and low physical activity. The data reflected patient performance status and discriminated between survival groups. Accelerometry can provide a useful measure for future interventional studies in patients with MPE

Trends in the Use of Feeding Tubes in North Carolina Hospitals: 1989 to 2000

OBJECTIVE: National data describing the placement of feeding tubes demonstrated a rapid increase in use in the early and mid-1990s. In the past several years, substantial concerns have arisen regarding the appropriateness of the procedure in many chronically ill patients. The purpose of this study is to determine whether the use of feeding tubes has continued to increase through the 1990s despite these widely publicized concerns. DESIGN: Repeated measure cross-sectional study of the North Carolina Discharge Database. SETTING: Analyses of all nonfederal hospital inpatient admissions in North Carolina. MEASUREMENTS AND MAIN RESULTS: We examined the absolute numbers and rates of feeding tube placements from 1989 to 2000. The rate of feeding tube placement increased from 59/100,000 persons in 1989 to 94/100,000 persons in 2000, an overall 60% increase with slowing in the rate of increase in the late 1990s. However, when outpatient procedures were included, the increase in tube feeding continued throughout the 11-year period of observation. The increase was due to an increase in utilization within all hospitals over the time period. Utilization did not differ between profit and not for profit hospitals. The relative growth rate of inpatient feeding tube placement did not differ by age group but the absolute increase was greatest in those age 75 years and over. CONCLUSIONS: Our study demonstrates that the use of feeding tubes has continued to increase through the 1990s. This increase occurred despite ongoing controversy in the medical literature about feeding tube placement in chronically ill patients