EGI: anOpen e-Infrastructure Ecosystem for the Digital European Research Area

Bringing the digital European Research Area (ERA) online means modernising Europe’s research infrastructure by promoting open science through the availability, accessibility and reuse of scientific data and results, the use of web- based tools that facilitate scientific collaboration and ensuring public access to research. As the European Grid Infrastructure (EGI) is the largest European distributed computing infrastructure providing 24/7 access to large scale computing, storage and data resources through a federation of national resource providers, it allows scientists from all disciplines to make the most out of the latest computing technologies for the benefit of their research. This paper describes the methodology and approach for defining EGI’s role in bringing this digital ERA online. The work presented defines the roles and functions of EGI as an open ICT ecosystem, required service redesign, the added value of EGI for the European research communities and demonstrates the role that EGI plays in contributing to the Europe 2020 strategy for social-economic impact

Towards Grid Interoperability

The Grid paradigm promises to provide global access to computing resources, data storage and experimental instruments. It also provides an elegant solution to many resource administration and provisioning problems while offering a platform for collaboration and resource sharing. Although substantial progress has been made towards these goals, nevertheless there is still a lot of work to be done until the Grid can deliver its promises. One of the central issues is the development of standards and Grid interoperability. Job execution is one of the key capabilities in all Grid environments. This is a well understood, mature area with standards and implementations. This paper describes some proof of concept experiments demonstrating the interoperability between various Grid environments

User Priorities for Data: Results from SUPER

SUPER, a Study of User Priorities for e-infrastructure for Research, was a six-month effort funded by the UK e-Science Core Programme and JISC. Its aim was to inform investment in order to provide a usable, useful, and accessible e-infrastructure for all researchers and a coherent set of e-infrastructure services that would increase usage by at least a factor of ten by 2010. Through a series of unstructured face-to-face interviews with over 45 participants from 30 different projects, an online survey, together with a day-long workshop at NeSC, we have observed recurring issues relating to the provision of e-infrastructure. In this article we focus on the data-related issues identified during these interactions. We conclude with a prioritised list of future activities for research, development, and adoption in the data space

The OMII Software Distribution

This paper describes the work carried out at the Open Middleware Infrastructure Institute (OMII) and the key elements of the OMII software distribution that have been developed in collaboration with members of the Managed Programme Initiative. The main objective of the OMII is to preserve and consolidate the achievements of the UK e-Science Programme by collecting, maintaining and improving the software modules that form the key components of a generic Grid middleware. Recently, the activity at Southampton has been extended beyond 2009 through a new project, OMII-UK, that forms a partnership that now includes the OGSA-DAI activities at Edinburgh and the myGrid project at Manchester

Common ELIXIR Service for Researcher Authentication and Authorisation

Linden M, Prochazka M, Lappalainen I, et al. Common ELIXIR Service for Researcher Authentication and Authorisation. F1000Research. 2018;7: 1199.A common Authentication and Authorisation Infrastructure (AAI) that would allow single sign-on to services has been identified as a key enabler for European bioinformatics. ELIXIR AAI is an ELIXIR service portfolio for authenticating researchers to ELIXIR services and assisting these services on user privileges during research usage. It relieves the scientific service providers from managing the user identities and authorisation themselves, enables the researcher to have a single set of credentials to all ELIXIR services and supports meeting the requirements imposed by the data protection laws. ELIXIR AAI was launched in late 2016 and is part of the ELIXIR Compute platform portfolio. By the end of 2017 the number of users reached 1000, while the number of relying scientific services was 36. This paper presents the requirements and design of the ELIXIR AAI and the policies related to its use, and how it can be used for serving some example services, such as document management, social media, data discovery, human data access, cloud compute and training services

Genetic Risk as a Marker of Amyloid-β and Tau Burden in Cerebrospinal Fluid.

BACKGROUND: The search for a biomarker of Alzheimer's disease (AD) pathology (amyloid-β (Aβ) and tau) is ongoing, with the best markers currently being measurements of Aβ and tau in cerebrospinal fluid (CSF) and via positron emission tomography (PET) scanning. These methods are relatively invasive, costly, and often have high screening failure rates. Consequently, research is aiming to elucidate blood biomarkers of Aβ and tau. OBJECTIVE: This study aims to investigate a case/control polygenic risk score (PGRS) as a marker of tau and investigate blood markers of a combined Aβ and tau outcome for the first time. A sub-study also considers plasma tau as markers of Aβ and tau pathology in CSF. METHODS: We used data from the EDAR*, DESCRIPA**, and Alzheimer's Disease Neuroimaging Initiative (ADNI) cohorts in a logistic regression analysis to investigate blood markers of Aβ and tau in CSF. In particular, we investigated the extent to which a case/control PGRS is predictive of CSF tau, CSF amyloid, and a combined amyloid and tau outcome. The predictive ability of models was compared to that of age, gender, and APOE genotype ('basic model'). RESULTS: In EDAR and DESCRIPA test data, inclusion of a case/control PGRS was no more predictive of Aβ, and a combined Aβ and tau endpoint than the basic models (accuracies of 66.0%, and 73.3% respectively). The tau model saw a small increase in accuracy compared to basic models (59.6%). ADNI 2 test data also showed a slight increase in accuracy for the Aβ model when compared to the basic models (61.4%). CONCLUSION: We see some evidence that a case/control PGRS is marginally more predictive of Aβ and tau pathology than the basic models. The search for predictive factors of Aβ and tau pathologies, above and beyond demographic information, is still ongoing. Better understanding of AD risk alleles, development of more sensitive assays, and studies of larger sample size are three avenues that may provide such factors. However, the clinical utility of possible predictors of brain Aβ and tau pathologies must also be investigated.*'Beta amyloid oligomers in the early diagnosis of AD and as marker for treatment response'**'Development of screening guidelines and criteria for pre-dementia Alzheimer's disease'.Multiple funders listed on paper

Circulating Proteomic Signatures of Chronological Age

To elucidate the proteomic features of aging in plasma, the subproteome targeted by the SOMAscan assay was profiled in blood samples from 202 females from the TwinsUK cohort. Findings were replicated in 677 independent individuals from the AddNeuroMed, Alzheimer's Research UK, and Dementia Case Registry cohorts. Results were further validated using RNAseq data from whole blood in TwinsUK and the most significant proteins were tested for association with aging-related phenotypes after adjustment for age. Eleven proteins were associated with chronological age and were replicated at protein level in an independent population. These were further investigated at gene expression level in 384 females from the TwinsUK cohort. The two most strongly associated proteins were chordin-like protein 1 (meta-analysis β [SE] = 0.013 [0.001], p = 3.66 × 10−46) and pleiotrophin (0.012 [0.005], p = 3.88 × 10−41). Chordin-like protein 1 was also significantly correlated with birthweight (0.06 [0.02], p = 0.005) and with the individual Framingham 10-years cardiovascular risk scores in TwinsUK (0.71 [0.18], p = 9.9 × 10−5). Pleiotrophin is a secreted growth factor with a plethora of functions in multiple tissues and known to be a marker for cardiovascular risk and osteoporosis. Our study highlights the importance of proteomics to identify some molecular mechanisms involved in human health and agin

A Pathway Based Classification Method for Analyzing Gene Expression for Alzheimer's Disease Diagnosis.

BACKGROUND: Recent studies indicate that gene expression levels in blood may be able to differentiate subjects with Alzheimer's disease (AD) from normal elderly controls and mild cognitively impaired (MCI) subjects. However, there is limited replicability at the single marker level. A pathway-based interpretation of gene expression may prove more robust. OBJECTIVES: This study aimed to investigate whether a case/control classification model built on pathway level data was more robust than a gene level model and may consequently perform better in test data. The study used two batches of gene expression data from the AddNeuroMed (ANM) and Dementia Case Registry (DCR) cohorts. METHODS: Our study used Illumina Human HT-12 Expression BeadChips to collect gene expression from blood samples. Random forest modeling with recursive feature elimination was used to predict case/control status. Age and APOE ɛ4 status were used as covariates for all analysis. RESULTS: Gene and pathway level models performed similarly to each other and to a model based on demographic information only. CONCLUSIONS: Any potential increase in concordance from the novel pathway level approach used here has not lead to a greater predictive ability in these datasets. However, we have only tested one method for creating pathway level scores. Further, we have been able to benchmark pathways against genes in datasets that had been extensively harmonized. Further work should focus on the use of alternative methods for creating pathway level scores, in particular those that incorporate pathway topology, and the use of an endophenotype based approach

Concise total synthesis of (+)-gliocladins B and C

The first total synthesis of (+)-gliocladin B is described. Our concise and enantioselective synthesis takes advantage of a new regioselective Friedel–Crafts-based strategy to provide an efficient multigram-scale access to the C3-(3′-indolyl)hexahydropyrroloindole substructure, a molecular foundation present in a significant subset of epipolythiodiketopiperazine natural alkaloids. Our first-generation solution to (+)-gliocladin B involved the stereoselective formation of (+)-12-deoxybionectin A, a plausible biosynthetic precursor. Our synthesis clarified the C15 stereochemistry of (+)-gliocladin B and allowed its full structure confirmation. Further studies of a versatile dihydroxylated diketopiperazine provided a concise and efficient synthesis of (+)-gliocladin B as well as access to (+)-gliocladin C.National Institute of General Medical Sciences (U.S.) (GM089732)Amgen Inc.National Science Foundation (U.S.) (CHE-0946721