The Blood Ontology: An ontology in the domain of hematology

Despite the importance of human blood to clinical practice and research, hematology and blood transfusion data remain scattered throughout a range of disparate sources. This lack of systematization concerning the use and definition of terms poses problems for physicians and biomedical professionals. We are introducing here the Blood Ontology, an ongoing initiative designed to serve as a controlled vocabulary for use in organizing information about blood. The paper describes the scope of the Blood Ontology, its stage of development and some of its anticipated uses

The skewness of science in 219 sub-fields and a number of aggregates

This paper studies evidence from Thomson Scientific about the citation process of 3.7 million articles published in the period 1998-2002 in 219 Web of Science categories, or sub-fields. Reference and citation distributions have very different characteristics across sub-fields. However, when analyzed with the Characteristic Scores and Scales technique, which is replication and scale invariant, the shape of these distributions over three broad categories of articles appears strikingly similar. Reference distributions are mildly skewed, but citation distributions with a five-year citation window are highly skewed: the mean is twenty points above the median, while 9-10% of all articles in the upper tail account for about 44% of all citations. The aggregation of sub-fields into disciplines and fields according to several aggregation schemes preserve this feature of citation distributions. It should be noted that when we look into subsets of articles within the lower and upper tails of citation distributions the universality partially breaks down. On the other hand, for 140 of the 219 sub-fields the existence of a power law cannot be rejected. However, contrary to what is generally believed, at the sub-field level the scaling parameter is above 3.5 most of the time, and power laws are relatively small: on average, they represent 2% of all articles and account for 13.5% of all citations. The results of the aggregation into disciplines and fields reveal that power law algebra is a subtle phenomenon.

Key environmental stress biomarker candidates for the optimisation of chemotherapy treatment of leukaemia

The impact of fluctuations of environmental parameters such as oxygen and starvation on the evolution of leukaemia is analysed in the current review. These fluctuations may occur within a specific patient (in different organs) or across patients (individual cases of hypoglycaemia and hyperglycaemia). They can be experienced as stress stimuli by the cancerous population, leading to an alteration of cellular growth kinetics, metabolism and further resistance to chemotherapy. Therefore, it is of high importance to elucidate key mechanisms that affect the evolution of leukaemia under stress. Potential stress response mechanisms are discussed in this review. Moreover, appropriate cell biomarker candidates related to the environmental stress response and/or further resistance to chemotherapy are proposed. Quantification of these biomarkers can enable the combination of macroscopic kinetics with microscopic information, which is specific to individual patients and leads to the construction of detailed mathematical models for the optimisation of chemotherapy. Due to their nature, these models will be more accurate and precise (in comparison to available macroscopic/black box models) in the prediction of responses of individual patients to treatment, as they will incorporate microscopic genetic and/or metabolic information which is patient-specific.peer-reviewe

The skewness of science in 219 sub-fields and a number of aggregates

This paper studies evidence from Thomson Scientific about the citation process of 3.7 million articles published in the period 1998-2002 in 219 Web of Science categories, or sub-fields. Reference and citation distributions have very different characteristics across sub-fields. However, when analyzed with the Characteristic Scores and Scales technique, which is size and scale independent, the shape of these distributions appear extraordinarily similar. Reference distributions are mildly skewed, but citation distributions with a five-year citation window are highly skewed: the mean is twenty points above the median, while 9-10% of all articles in the upper tail account for about 44% of all citations. The aggregation of sub-fields into disciplines and fields according to several aggregation schemes preserve this feature of citation distributions. On the other hand, for 140 of the 219 sub-fields the existence of a power law cannot be rejected. However, contrary to what is generally believed, at the sub-field level the scaling parameter is above 3.5 most of the time, and power laws are relatively small: on average, they represent 2% of all articles and account for 13.5% of all citations. The results of the aggregation into disciplines and fields reveal that power law algebra is a subtle phenomenon.

Exploring the relationship between the Engineering and Physical Sciences and the Health and Life Sciences by advanced bibliometric methods

We investigate the extent to which advances in the health and life sciences (HLS) are dependent on research in the engineering and physical sciences (EPS), particularly physics, chemistry, mathematics, and engineering. The analysis combines two different bibliometric approaches. The first approach to analyze the 'EPS-HLS interface' is based on term map visualizations of HLS research fields. We consider 16 clinical fields and five life science fields. On the basis of expert judgment, EPS research in these fields is studied by identifying EPS-related terms in the term maps. In the second approach, a large-scale citation-based network analysis is applied to publications from all fields of science. We work with about 22,000 clusters of publications, each representing a topic in the scientific literature. Citation relations are used to identify topics at the EPS-HLS interface. The two approaches complement each other. The advantages of working with textual data compensate for the limitations of working with citation relations and the other way around. An important advantage of working with textual data is in the in-depth qualitative insights it provides. Working with citation relations, on the other hand, yields many relevant quantitative statistics. We find that EPS research contributes to HLS developments mainly in the following five ways: new materials and their properties; chemical methods for analysis and molecular synthesis; imaging of parts of the body as well as of biomaterial surfaces; medical engineering mainly related to imaging, radiation therapy, signal processing technology, and other medical instrumentation; mathematical and statistical methods for data analysis. In our analysis, about 10% of all EPS and HLS publications are classified as being at the EPS-HLS interface. This percentage has remained more or less constant during the past decade

Using in silico models to simulate dual perturbation experiments: procedure development and interpretation of outcomes.

BackgroundA growing number of realistic in silico models of metabolic functions are being formulated and can serve as 'dry lab' platforms to prototype and simulate experiments before they are performed. For example, dual perturbation experiments that vary both genetic and environmental parameters can readily be simulated in silico. Genetic and environmental perturbations were applied to a cell-scale model of the human erythrocyte and subsequently investigated.ResultsThe resulting steady state fluxes and concentrations, as well as dynamic responses to the perturbations were analyzed, yielding two important conclusions: 1) that transporters are informative about the internal states (fluxes and concentrations) of a cell and, 2) that genetic variations can disrupt the natural sequence of dynamic interactions between network components. The former arises from adjustments in energy and redox states, while the latter is a result of shifting time scales in aggregate pool formation of metabolites. These two concepts are illustrated for glucose-6 phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) in the human red blood cell.ConclusionDual perturbation experiments in silico are much more informative for the characterization of functional states than single perturbations. Predictions from an experimentally validated cellular model of metabolism indicate that the measurement of cofactor precursor transport rates can inform the internal state of the cell when the external demands are altered or a causal genetic variation is introduced. Finally, genetic mutations that alter the clinical phenotype may also disrupt the 'natural' time scale hierarchy of interactions in the network

Systems biology in animal sciences

Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes and animal traits are not yet frequently used. This paper aims to explain what systems biology is and which areas of animal sciences could benefit from systems biology approaches. Systems biology aims to understand whole biological systems working as a unit, rather than investigating their individual components. Therefore, systems biology can be considered a holistic approach, as opposed to reductionism. The recently developed ‘omics’ technologies enable biological sciences to characterize the molecular components of life with ever increasing speed, yielding vast amounts of data. However, biological functions do not follow from the simple addition of the properties of system components, but rather arise from the dynamic interactions of these components. Systems biology combines statistics, bioinformatics and mathematical modeling to integrate and analyze large amounts of data in order to extract a better understanding of the biology from these huge data sets and to predict the behavior of biological systems. A ‘system’ approach and mathematical modeling in biological sciences are not new in itself, as they were used in biochemistry, physiology and genetics long before the name systems biology was coined. However, the present combination of mass biological data and of computational and modeling tools is unprecedented and truly represents a major paradigm shift in biology. Significant advances have been made using systems biology approaches, especially in the field of bacterial and eukaryotic cells and in human medicine. Similarly, progress is being made with ‘system approaches’ in animal sciences, providing exciting opportunities to predict and modulate animal traits

Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium

Funding text The authors are grateful for the vital contributions of the participating study volunteers, clinicians, nurses, and laboratory technicians at the Surrey study site. The work by Roberto Leone, laboratory technician at Humanitas Clinical and Research Center, is gratefully acknowledged. Finally, they thank Ellen Oe (GSK) for scientific writing assistance. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115308, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in-kind contribution. The contribution of the European Commission to the Advanced Immunization Technologies (ADITEC) project (grant agreement n° 280873) is also gratefully acknowledged. Publisher Copyright: © 2019, The Author(s).Biomarkers predictive of inflammatory events post-vaccination could accelerate vaccine development. Within the BIOVACSAFE framework, we conducted three identically designed, placebo-controlled inpatient/outpatient clinical studies (NCT01765413/NCT01771354/NCT01771367). Six antiviral vaccination strategies were evaluated to generate training data-sets of pre-/post-vaccination vital signs, blood changes and whole-blood gene transcripts, and to identify putative biomarkers of early inflammation/reactogenicity that could guide the design of subsequent focused confirmatory studies. Healthy adults (N = 123; 20–21/group) received one immunization at Day (D)0. Alum-adjuvanted hepatitis B vaccine elicited vital signs and inflammatory (CRP/innate cells) responses that were similar between primed/naive vaccinees, and low-level gene responses. MF59-adjuvanted trivalent influenza vaccine (ATIV) induced distinct physiological (temperature/heart rate/reactogenicity) response-patterns not seen with non-adjuvanted TIV or with the other vaccines. ATIV also elicited robust early (D1) activation of IFN-related genes (associated with serum IP-10 levels) and innate-cell-related genes, and changes in monocyte/neutrophil/lymphocyte counts, while TIV elicited similar but lower responses. Due to viral replication kinetics, innate gene activation by live yellow-fever or varicella-zoster virus (YFV/VZV) vaccines was more suspended, with early IFN-associated responses in naïve YFV-vaccine recipients but not in primed VZV-vaccine recipients. Inflammatory responses (physiological/serum markers, innate-signaling transcripts) are therefore a function of the vaccine type/composition and presence/absence of immune memory. The data reported here have guided the design of confirmatory Phase IV trials using ATIV to provide tools to identify inflammatory or reactogenicity biomarkers.Peer reviewe

T-ALL and thymocytes : a message of noncoding RNAs

In the last decade, the role for noncoding RNAs in disease was clearly established, starting with microRNAs and later expanded towards long noncoding RNAs. This was also the case for T cell acute lymphoblastic leukemia, which is a malignant blood disorder arising from oncogenic events during normal T cell development in the thymus. By studying the transcriptomic profile of protein-coding genes, several oncogenic events leading to T cell acute lymphoblastic leukemia (T-ALL) could be identified. In recent years, it became apparent that several of these oncogenes function via microRNAs and long noncoding RNAs. In this review, we give a detailed overview of the studies that describe the noncoding RNAome in T-ALL oncogenesis and normal T cell development