Implementing the reuse of public DIA proteomics datasets: from the PRIDE database to Expression Atlas.

The number of mass spectrometry (MS)-based proteomics datasets in the public domain keeps increasing, particularly those generated by Data Independent Acquisition (DIA) approaches such as SWATH-MS. Unlike Data Dependent Acquisition datasets, the re-use of DIA datasets has been rather limited to date, despite its high potential, due to the technical challenges involved. We introduce a (re-)analysis pipeline for public SWATH-MS datasets which includes a combination of metadata annotation protocols, automated workflows for MS data analysis, statistical analysis, and the integration of the results into the Expression Atlas resource. Automation is orchestrated with Nextflow, using containerised open analysis software tools, rendering the pipeline readily available and reproducible. To demonstrate its utility, we reanalysed 10 public DIA datasets from the PRIDE database, comprising 1,278 SWATH-MS runs. The robustness of the analysis was evaluated, and the results compared to those obtained in the original publications. The final expression values were integrated into Expression Atlas, making SWATH-MS experiments more widely available and combining them with expression data originating from other proteomics and transcriptomics datasets.

Experimental determination of configurational entropy in a two-dimensional liquid under random pinning.

A quasi two-dimensional colloidal suspension is studied under the influence of immobilisation (pinning) of a random fraction of its particles. We introduce a novel experimental method to perform random pinning and, with the support of numerical simulation, we find that increasing the pinning concentration smoothly arrests the system, with a cross-over from a regime of high mobility and high entropy to a regime of low mobility and low entropy. At the local level, we study fluctuations in area fraction and concentration of pins and map them to entropic structural signatures and local mobility, obtaining a measure for the local entropic fluctuations of the experimental system.

Weak temperature dependence of ageing of structural properties in atomistic model glassformers.

Ageing phenomena are investigated from a structural perspective in two binary Lennard-Jones glassformers, the Kob-Andersen and Wahnström mixtures. In both, the geometric motif assumed by the glassformer upon supercooling, the locally favoured structure (LFS), has been established. The Kob-Andersen mixture forms bicapped square antiprisms; the Wahnström model forms icosahedra. Upon ageing, we find that the structural relaxation time has a time-dependence consistent with a power law. However, the LFS population and potential energy increase and decrease, respectively, in a logarithmic fashion. Remarkably, over the time scales investigated, which correspond to a factor of 104 change in relaxation times, the rate at which these quantities age appears almost independent of temperature. Only at temperatures far below the Vogel-Fulcher-Tamman temperature do the ageing dynamics slow.

The nature of geometric frustration in the Kob-Andersen mixture.

Geometric frustration is an approach to the glass transition based upon the consideration of locally favoured structures (LFS), which are geometric motifs which minimise the local free energy. Geometric frustration proposes that a transition to a crystalline state is frustrated because these LFS do not tile space. However, this concept is based on icosahedra which are not always the LFS for a given system. The LFS of the popular Kob-Andersen (KA) model glassformer are the bicapped square antiprism, which does tile space. Such a LFS-crystal is indeed realised in the Al2Cu structure, which is predicted to be a low energy state for the KA model with a 2:1 composition. We, therefore, hypothesise that upon changing the composition in the KA model towards 2:1, geometric frustration may be progressively relieved, leading to larger and larger domains of LFS which would ultimately correspond to the Al2Cu crystal. Remarkably, rather than an increase, upon changing composition we find a small decrease in the LFS population, and the system remains impervious to nucleation of LFS crystals. We suggest that this may be related to the composition of the LFS, as only a limited subset is compatible with the crystal. We further demonstrate that the Al2Cu crystal will grow from a seed in the KA model with 2:1 composition and identify the melting temperature to be 0.447(2).

A software tool to aid long-term care budget planning at local authority level.

OBJECTIVE: Local authorities face real challenges when it comes to annual budget planning for funding the system of long-term care. Uncertainty about the long-term cost of caring for current residents in the system, in addition to unknown future admissions, have made the tasks of local authority budget managers very complex and demanding. In this paper, we present a software implementation of a novel forecasting framework developed by the authors to provide useful information to local authority budget planners involved in long-term care. METHODS: The tool is built upon a forecasting framework, which combines unit costs of care with an estimated underlying survival model for publicly funded residents in long-term care, to provide forecasts of the cost of maintaining the group of elderly people who are currently in long-term care (referred to as known commitments) for a period of time. A prototype version of the software tool, which was created and tested in collaboration with an English borough, allows user interaction via a friendly graphical interface that guides through a set of screens of options in a familiar wizard fashion. RESULTS AND DISCUSSION: Feedback from care planners and managers show that the tool helps them gain better understanding of the patterns of length-of-stay of residents under their care, and provides quantitative inputs into their decision making on budget planning for long-term care. The development of the software tool brings advanced modelling techniques out of research papers into the hands of decision makers in the public sector and contributes to improving the delivery of long-term care.

A software tool to aid budget planning for long-term care at local authority level.

In this paper, we present a software tool that implements a novel modelling framework developed by the authors to provide useful information to budget planners for long-term care at local authority level. By combining unit costs of care with an underlying survival model for publicly funded residents in long-term care, the software tool is able to provide forecasts on the cost of maintaining the group of elderly who are currently in long-term care (referred to as known commitments) for a period of time. User interacts with the tool via a friendly graphical interface that guides them through a set of screens of options in a familiar wizard fashion. This tool was created and tested in collaboration with an English borough. Feedbacks from the care planner and manager show that the tool helps them gain better understanding on the behaviour of length-of-stay of residents under their care, and provides quantitative inputs into their decision making on budget planning for long-term care.

Involving older people in research: methodological issues.

The policy imperative to increase public participation in health and social care research, planning and service delivery raises significant questions about optimum approaches, methods and the extent to which this policy can influence change in practice. This paper highlights the key policy literature on user involvement and participatory research methods to establish the context for a partnership research project exploring perceptions of risk in relation to falls from the perspectives of older people, carers, and health and social care professionals. The paper reports the methods used in developing user involvement in the research at a number of levels, including project management, and a consumer panel working alongside the research team and influencing the dissemination in local falls prevention strategies. The authors draw out the issues related to the context and method of involvement, and discuss the impact on research quality and local service development in health and social care.