Quantifying habitual levels of physical activity according to impact in older people: accelerometry protocol for the VIBE study

Physical activity (PA) may need to produce high impacts to be osteogenic. The aim of this study was to identify threshold(s) for defining high impact PA for future analyses in the VIBE (Vertical Impact and Bone in the Elderly) study, based on home recordings with triaxial accelerometers. Recordings were obtained from 19 Master Athlete Cohort (MAC; mean 67.6 years) and 15 Hertfordshire Cohort Study (HCS; mean 77.7 years) participants. Data cleaning protocols were developed to exclude artifacts. Accelerations expressed in g units were categorized into three bands selected from the distribution of positive Y-axis peak accelerations. Data were available for 6.6 and 4.4 days from MAC and HCS participants respectively, with approximately 14 hr recording daily. Three-fold more 0.5–1.0g impacts were observed in MAC versus HCS, 20-fold more 1.0–1.5g impacts, and 140-fold more impacts ≥ 1.5g. Our analysis protocol successfully distinguishes PA levels in active and sedentary older individuals

Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet

Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; smoking is the main risk factor for COPD, but genetic factors are also relevant contributors. Genome-wide association studies (GWAS) of the lung function measures used in the diagnosis of COPD have identified a number of loci, however association signals are often broad and collectively these loci only explain a small proportion of the heritability. In order to examine the association with COPD risk of genetic variants down to low allele frequencies, to aid fine-mapping of association signals and to explain more of the missing heritability, we undertook a targeted sequencing study in 300 COPD cases and 300 smoking controls for 26 loci previously reported to be associated with lung function. We used a pooled sequencing approach, with 12 pools of 25 individuals each, enabling high depth (30x) coverage per sample to be achieved. This pooled design maximised sample size and therefore power, but led to challenges during variant-calling since sequencing error rates and minor allele frequencies for rare variants can be very similar. For this reason we employed a rigorous quality control pipeline for variant detection which included the use of 3 independent calling algorithms. In order to avoid false positive associations we also developed tests to detect variants with potential batch effects and removed them before undertaking association testing. We tested for the effects of single variants and the combined effect of rare variants within a locus. We followed up the top signals with data available (only 67% of collapsing methods signals) in 4,249 COPD cases and 11,916 smoking controls from UK Biobank. We provide suggestive evidence for the combined effect of rare variants on COPD risk in TNXB and in sliding windows within MECOM and upstream of HHIP. These findings can lead to an improved understanding of the molecular pathways involved in the development of COPD

Bayesian inversion of synthetic AVO data to assess fluid and shale content in sand-shale media

Reservoir characterization of sand-shale sequences has always challenged geoscientists due to the presence of anisotropy in the form of shale lenses or shale layers. Water saturation and volume of shale are among the fundamental reservoir properties of interest for sand-shale intervals, and relate to the amount of fluid content and accumulating potentials of such media. This paper suggests an integrated workflow using synthetic data for the characterization of shaley-sand media based on anisotropic rock physics (T-matrix approximation) and seismic reflectivity modelling. A Bayesian inversion scheme for estimating reservoir parameters from amplitude vs. offset (AVO) data was used to obtain the information about uncertainties as well as their most likely values. The results from our workflow give reliable estimates of water saturation from AVO data at small uncertainties, provided background sand porosity values and isotropic overburden properties are known. For volume of shale, the proposed workflow provides reasonable estimates even when larger uncertainties are present in AVO data

An ontology for major histocompatibility restriction

BACKGROUND: MHC molecules are a highly diverse family of proteins that play a key role in cellular immune recognition. Over time, different techniques and terminologies have been developed to identify the specific type(s) of MHC molecule involved in a specific immune recognition context. No consistent nomenclature exists across different vertebrate species. PURPOSE: To correctly represent MHC related data in The Immune Epitope Database (IEDB), we built upon a previously established MHC ontology and created an ontology to represent MHC molecules as they relate to immunological experiments. DESCRIPTION: This ontology models MHC protein chains from 16 species, deals with different approaches used to identify MHC, such as direct sequencing verses serotyping, relates engineered MHC molecules to naturally occurring ones, connects genetic loci, alleles, protein chains and multi-chain proteins, and establishes evidence codes for MHC restriction. Where available, this work is based on existing ontologies from the OBO foundry. CONCLUSIONS: Overall, representing MHC molecules provides a challenging and practically important test case for ontology building, and could serve as an example of how to integrate other ontology building efforts into web resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13326-016-0045-5) contains supplementary material, which is available to authorized users

Towards the reconstruction of the genome-scale metabolic model of Lactobacillus acidophilus La-14

Lactobacillus acidophilus is a probiotic lactic acid bacterium used in food and dietary supplements for many years. However, despite its importance for industrial development and recognized health-promoting effects, no genome-scale metabolic model has been reported. A GSM model for L. acidophilus La-14 was developed, accounting 494 genes and 783 reactions. A genome annotation was performed to identify the metabolic potential of the bacterium. The biomass composition was determined based on information available in literature and previously published models. The model was validated by comparing in silico simulations with experimental data, regarding the aerobic and anaerobic growth. The reconstruction of the metabolic model has confirmed the fastidious requirements of L. acidophilus for amino acids, fatty acids, and vitamins. This model can be used for a better understanding of the metabolism of this bacterium and identification of industrially desirable compounds.This study was performed under the scope of the project “BIODATA.PT – Portuguese Biological Data Network” (ref. LISBOA-01-0145-FEDER-022231), funded by FCT/MCTES, through national funds of PIDDAC, Fundo Europeu de Desenvolvimento Regional (FEDER), Programa Operacional de Competitividade e Internacionalização (POCI) and Programa Operacional Regional de Lisboa (Lisboa 2020).info:eu-repo/semantics/publishedVersio

Applying unmixing to gene expression data for tumor phylogeny inference

<p>Abstract</p> <p>Background</p> <p>While in principle a seemingly infinite variety of combinations of mutations could result in tumor development, in practice it appears that most human cancers fall into a relatively small number of "sub-types," each characterized a roughly equivalent sequence of mutations by which it progresses in different patients. There is currently great interest in identifying the common sub-types and applying them to the development of diagnostics or therapeutics. Phylogenetic methods have shown great promise for inferring common patterns of tumor progression, but suffer from limits of the technologies available for assaying differences between and within tumors. One approach to tumor phylogenetics uses differences between single cells within tumors, gaining valuable information about intra-tumor heterogeneity but allowing only a few markers per cell. An alternative approach uses tissue-wide measures of whole tumors to provide a detailed picture of averaged tumor state but at the cost of losing information about intra-tumor heterogeneity.</p> <p>Results</p> <p>The present work applies "unmixing" methods, which separate complex data sets into combinations of simpler components, to attempt to gain advantages of both tissue-wide and single-cell approaches to cancer phylogenetics. We develop an unmixing method to infer recurring cell states from microarray measurements of tumor populations and use the inferred mixtures of states in individual tumors to identify possible evolutionary relationships among tumor cells. Validation on simulated data shows the method can accurately separate small numbers of cell states and infer phylogenetic relationships among them. Application to a lung cancer dataset shows that the method can identify cell states corresponding to common lung tumor types and suggest possible evolutionary relationships among them that show good correspondence with our current understanding of lung tumor development.</p> <p>Conclusions</p> <p>Unmixing methods provide a way to make use of both intra-tumor heterogeneity and large probe sets for tumor phylogeny inference, establishing a new avenue towards the construction of detailed, accurate portraits of common tumor sub-types and the mechanisms by which they develop. These reconstructions are likely to have future value in discovering and diagnosing novel cancer sub-types and in identifying targets for therapeutic development.</p

Genetic Associations and Architecture of Asthma-COPD Overlap

BACKGROUND: Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. RESEARCH QUESTION: What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma? STUDY DESIGN AND METHODS: We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 × 10-6) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2). RESULTS: We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 × 10-8) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent. INTERPRETATION: We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma

A Signature Inferred from Drosophila Mitotic Genes Predicts Survival of Breast Cancer Patients

Introduction: The classification of breast cancer patients into risk groups provides a powerful tool for the identification of patients who will benefit from aggressive systemic therapy. The analysis of microarray data has generated several gene expression signatures that improve diagnosis and allow risk assessment. There is also evidence that cell proliferation-related genes have a high predictive power within these signatures. Methods: We thus constructed a gene expression signature (the DM signature) using the human orthologues of 108 Drosophila melanogaster genes required for either the maintenance of chromosome integrity (36 genes) or mitotic division (72 genes). Results: The DM signature has minimal overlap with the extant signatures and is highly predictive of survival in 5 large breast cancer datasets. In addition, we show that the DM signature outperforms many widely used breast cancer signatures in predictive power, and performs comparably to other proliferation-based signatures. For most genes of the DM signature, an increased expression is negatively correlated with patient survival. The genes that provide the highest contribution to the predictive power of the DM signature are those involved in cytokinesis. Conclusion: This finding highlights cytokinesis as an important marker in breast cancer prognosis and as a possible targe

Tasting Soil Fungal Diversity with Earth Tongues: Phylogenetic Test of SATé Alignments for Environmental ITS Data

An abundance of novel fungal lineages have been indicated by DNA sequencing of the nuclear ribosomal ITS region from environmental samples such as soil and wood. Although phylogenetic analysis of these novel lineages is a key component of unveiling the structure and diversity of complex communities, such analyses are rare for environmental ITS data due to the difficulties of aligning this locus across significantly divergent taxa. One potential approach to this issue is simultaneous alignment and tree estimation. We targeted divergent ITS sequences of the earth tongue fungi (Geoglossomycetes), a basal class in the Ascomycota, to assess the performance of SATé, recent software that combines progressive alignment and tree building. We found that SATé performed well in generating high-quality alignments and in accurately estimating the phylogeny of earth tongue fungi. Drawing from a data set of 300 sequences of earth tongues and progressively more distant fungal lineages, 30 insufficiently identified ITS sequences from the public sequence databases were assigned to the Geoglossomycetes. The association between earth tongues and plants has been hypothesized for a long time, but hard evidence is yet to be collected. The ITS phylogeny showed that four ectomycorrhizal isolates shared a clade with Geoglossum but not with Trichoglossum earth tongues, pointing to the significant potential inherent to ecological data mining of environmental samples. Environmental sampling holds the key to many focal questions in mycology, and simultaneous alignment and tree estimation, as performed by SATé, can be a highly efficient companion in that pursuit