UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

Biomimetic hollow mesoporous hydroxyapatite microsphere with controlled morphology, entrapment efficiency and degradability for cancer therapy.

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Elimination Therapy for the Endemic Malarias

Most malaria diagnosed outside endemic zones occurs in patients experiencing the consequences of what was likely a single infectious bite by an anopheline mosquito. A single species of parasite is nearly always involved and expert opinion on malaria chemotherapy uniformly prescribes species- and stage-specific treatments. However the vast majority of people experiencing malaria, those resident in endemic zones, do so repeatedly and very often with the involvement of two or more species and stages of parasite. Silent forms of these infections—asymptomatic and beyond the reach of diagnostics—may accumulate to form substantial and unchallenged reservoirs of infection. In such settings treating only the species and stage of malaria revealed by diagnosis and not others may not be sensible or appropriate. Developing therapeutic strategies that address all species and stages independently of diagnostic evidence may substantially improve the effectiveness of the control and elimination of endemic malaria

Lineage Divergence and Historical Gene Flow in the Chinese Horseshoe Bat (Rhinolophus sinicus)

PMCID: PMC3581519This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Assessment of public health impact of work-related asthma

<p>Abstract</p> <p>Background</p> <p>Asthma is among the most common chronic diseases in working-aged populations and occupational exposures are important causal agents. Our aims were to evaluate the best methods to assess occurrence, public health impact, and burden to society related to occupational or work-related asthma and to achieve comparable estimates for different populations.</p> <p>Methods</p> <p>We addressed three central questions: <b>1: What is the best method to assess the occurrence of occupational asthma? </b>We evaluated: 1) assessment of the occurrence of occupational asthma <it>per se</it>, and 2) assessment of adult-onset asthma and the population attributable fractions due to specific occupational exposures. <b>2: What are the best methods to assess public health impact and burden to society related to occupational or work-related asthma? </b>We evaluated methods based on assessment of excess burden of disease due to specific occupational exposures. <b>3: How to achieve comparable estimates for different populations? </b>We evaluated comparability of estimates of occurrence and burden attributable to occupational asthma based on different methods.</p> <p>Results</p> <p>Assessment of the occurrence of occupational asthma <it>per se </it>can be used in countries with good coverage of the identification system for occupational asthma, i.e. countries with well-functioning occupational health services. Assessment based on adult-onset asthma and population attributable fractions due to specific occupational exposures is a good approach to estimate the occurrence of occupational asthma at the population level. For assessment of public health impact from work-related asthma we recommend assessing excess burden of disease due to specific occupational exposures, including excess incidence of asthma complemented by an assessment of disability from it. International comparability of estimates can be best achieved by methods based on population attributable fractions.</p> <p>Conclusions</p> <p>Public health impact assessment for occupational asthma is central in prevention and health policy planning and could be improved by purposeful development of methods for assessing health benefits from preventive actions. Registry-based methods are suitable for evaluating time-trends of occurrence at a given population but for international comparisons they face serious limitations. Assessment of excess burden of disease due to specific occupational exposure is a useful measure, when there is valid information on population exposure and attributable fractions.</p

Prenatal Detection of Aneuploidy and Imbalanced Chromosomal Arrangements by Massively Parallel Sequencing

Fetal chromosomal abnormalities are the most common reasons for invasive prenatal testing. Currently, G-band karyotyping and several molecular genetic methods have been established for diagnosis of chromosomal abnormalities. Although these testing methods are highly reliable, the major limitation remains restricted resolutions or can only achieve limited coverage on the human genome at one time. The massively parallel sequencing (MPS) technologies which can reach single base pair resolution allows detection of genome-wide intragenic deletions and duplication challenging karyotyping and microarrays as the tool for prenatal diagnosis. Here we reported a novel and robust MPS-based method to detect aneuploidy and imbalanced chromosomal arrangements in amniotic fluid (AF) samples. We sequenced 62 AF samples on Illumina GAIIx platform and with averagely 0.01× whole genome sequencing data we detected 13 samples with numerical chromosomal abnormalities by z-test. With up to 2× whole genome sequencing data we were able to detect microdeletion/microduplication (ranged from 1.4 Mb to 37.3 Mb of 5 samples from chorionic villus sampling (CVS) using SeqSeq algorithm. Our work demonstrated MPS is a robust and accurate approach to detect aneuploidy and imbalanced chromosomal arrangements in prenatal samples

Brain Activity in Fairness Consideration during Asset Distribution: Does the Initial Ownership Play a Role?

Previous behavioral studies have shown that initial ownership influences individuals’ fairness consideration and other-regarding behavior. However, it is not entirely clear whether initial ownership influences the brain activity when a recipient evaluates the fairness of asset distribution. In this study, we randomly assigned the bargaining property (monetary reward) to either the allocator or the recipient in the ultimatum game and let participants of the study, acting as recipients, receive either disadvantageous unequal, equal, or advantageous unequal offers from allocators while the event-related potentials (ERPs) were recorded. Behavioral results showed that participants were more likely to reject disadvantageous unequal and equal offers when they initially owned the property as compared to when they did not. The two types of unequal offers evoked more negative going ERPs (the MFN) than the equal offers in an early time window and the differences were not modulated by the initial ownership. In a late time window, however, the P300 responses to division schemes were affected not only by the type of unequal offers but also by whom the property was initially assigned to. These findings suggest that while the MFN may function as a general mechanism that evaluates whether the offer is consistent or inconsistent with the equity rule, the P300 is sensitive to top-down controlled processes, into which factors related to the allocation of attentional resources, including initial ownership and personal interests, come to play

Skewed Distribution of Circulating Activated Natural Killer T (NKT) Cells in Patients with Common Variable Immunodeficiency Disorders (CVID)

Common variable immunodeficiency disorder (CVID) is the commonest cause of primary antibody failure in adults and children, and characterized clinically by recurrent bacterial infections and autoimmune manifestations. Several innate immune defects have been described in CVID, but no study has yet investigated the frequency, phenotype or function of the key regulatory cell population, natural killer T (NKT) cells. We measured the frequencies and subsets of NKT cells in patients with CVID and compared these to healthy controls. Our results show a skewing of NKT cell subsets, with CD4+ NKT cells at higher frequencies, and CD8+ NKT cells at lower frequencies. However, these cells were highly activated and expression CD161. The NKT cells had a higher expression of CCR5 and concomitantly expression of CCR5+CD69+CXCR6 suggesting a compensation of the remaining population of NKT cells for rapid effector action